Patent Publication Number: US-2011071289-A1

Title: Aminopyrazole amide derivative

Description:
TECHNICAL FIELD 
     The invention relates to a pyrazole amide compound useful as a medicament. More specifically, the invention relates to a therapeutic or preventive agent for conditions related to glucocorticoid, or a pyrazole amide compound which is effective as an 11β hydroxysteroid dehydrogenase type 1 enzyme (referred to as 11βHSD1 hereinafter) inhibitor or 11βHSD1 modulator. The invention further relates to a therapeutic agent for diabetes that the active ingredient is a pyrazole amide compound which is effective as an 11βHSD1 inhibitor or 11βHSD1 modulator. 
     BACKGROUND ART 
     Glucocorticoid regulates peripheral glucose metabolism and amino acid metabolism. In human being, glucocorticoid is produced in adrenal gland and is metabolized in peripheral tissues including adipose tissue or liver. Since 11βHSD1 is an enzyme converting inactive cortisone into activated cortisol and is mainly expressed in adipose tissue or liver, 11βHSD1 is believed to be related to glucocorticoid activation in adipose tissue or liver. Cortisol shows promoting activities for fat accumulation in adipocyte or gluconeogenesis in liver, and hence, 11βHSD1 is believed to contribute to the maintenance of systemic homeostasis by adjusting glucose and/or lipid metabolism in periphery. On the other hand, in human insulin resistance patients, 11βHSD1 in adipose tissues was significantly increased in the activity, and the 11βHSD1 activity in visceral fat is remarkably higher than that in subcutaneous fat. In 11βHSD1 gene defect mice, development of visceral fat accumulation, glucose and/or lipid metabolism abnormality is suppressed on high-fat food feeding, and mice overexpressing adipocyte-specific 11βHSD1 show remarkable visceral fat-type obesity, or glucose and/or lipid metabolism abnormality. This indicates that an overactivation of 11βHSD1 is intimately related to development of visceral fat accumulation and/or metabolic syndrome in both human and mice. Specifically, advantageous effects including suppression of gluconeogenesis in liver and fat accumulation in adipocyte as well as improvement of systemic glucose and/or lipid metabolism are expected by inhibiting the enzyme activity. 
     As far the improvement of glucose metabolism, it has been reported that the 11βHSD1 activity in pancreatic β cells could relate to the suppression of insulin secretion and the 11βHSD1 activity could be involved in the suppression of glucose uptake in human muscle cells. Thus, an 11βHSD1 inhibitor has potential to improve hyperglycemia directly. 
     Additionally, 11βHSD1 has been shown to function in nerve cells or immunocytes, and the 11βHSD1 inhibitor is also expected to have therapeutic effects on diseases caused by the above abnormalities. 
     Various 11βHSD1 inhibitors have been reported. For example, it is reported that derivatives with pyrazole ring in Patent Document 1, and amide derivatives in Patent Document 2 are effective as 11βHSD1 inhibitor. 
     [Patent Document 1] WO2005/016877 pamphlet 
     [Patent Document 2] WO2004/089470 pamphlet 
     DISCLOSURE OF INVENTION 
     Problems to be Resolved by the Invention 
     A development of a pharmaceutically satisfiable compound which shows 11βHSD1 inhibitory effect as a therapeutic agent for preventing and/or treating diseases, including type II diabetes, abnormal glucose tolerance, hyperglycemia, insulin resistance, hypo-HDL-emia, hyper-LDL-emia, dyslipidemia, hyperlipidemia, hypertriglyceridemia, hypercholesterolemia, hypertension, arteriosclerosis, angiostenosis, atherosclerosis, obesity, cognitive disorder, glaucoma, retinopathy, dementia, Alzheimer disease, osteoporosis, immune disorder, syndrome X, depression, cardiovascular disease, neurodegenerative disease, has now been desired. 
     Means of Solving the Problems 
     Until now, the following [1] pyrazole-3-carboxylic acid amide derivatives of formula (1) has not been prepared for 11βHSD1 inhibitor, and the inhibitory activity thereof has been completely unknown. As a result of extensive studies of the derivatives in order to achieve the subject, the inventors have found that pyrazole-3-carboxylic acid amide derivatives of formula (1), which are substituted with alkyl etc. at 1-position and dialkylamino etc. at 5-position, have high 11βHSD1 inhibitory activity. 
     The inventors have found that pyrazole-3-carboxylic acid amide derivatives of formula (1) or pharmaceutically acceptable salts thereof, if needed, which are referred to as inventive compounds hereinafter, have an excellent 11βHSD1 inhibitory activity, and have achieved this invention. 
     Specifically, the invention relates to the following embodiments: 
     [1] A compound of formula (1): 
     
       
         
         
             
             
         
       
     
     wherein R A  and R B  are each independently optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, or a group of formula: —Rw—Rx—Ry—Rz; 
     Rw is, independently when it exists more than one, optionally substituted alkylene or optionally substituted cycloalkylene; 
     Rx is, independently when it exists more than one, a single bond, oxygen atom, or a group of formula: —S(O) n —, —C(O)—, —NR 3 —, —OC(O)—, —C(O)O—, —CONR 3 —, —NR 3 CO—, —SO 2 NR 3 —, —NR 3 SO 2 — or —NR 3 CONR 4 —; 
     Ry is, independently when it exists more than one, a single bond or optionally substituted alkylene; 
     Rz is, independently when it exists more than one, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted aryl, optionally substituted heteroaryl or optionally substituted heterocycloalkyl; 
     R 3  and R 4  are each independently hydrogen atom or optionally substituted alkyl; 
     n is 0, 1 or 2; 
     R C  is optionally substituted alkyl, optionally substituted cycloalkyl or optionally substituted cycloalkylalkyl; 
     R D  is hydrogen atom, halogen atom, cyano or optionally substituted alkyl; 
     R E  is hydrogen atom or optionally substituted alkyl; 
     R F  is a group selected from the following formulae (G1): 
     
       
         
         
             
             
         
       
     
     wherein one of hydrogen atoms is a bond, which may be optionally substituted; 
     provided that if both R A  and R B  are selected from the following group X, then R F  is a group of the following formula (2): 
     
       
         
         
             
             
         
       
     
     A 1  is COOR 1 , CONR 1 R 2 , SO 2 NR 1 R 2 , COOR 1 -substituted alkyl, CONR 1 R 2 -substituted alkyl, or SO 2 NR 1 R 2 -substituted alkyl, R 1  and R 2  are each independently hydrogen atom or optionally substituted alkyl, or R 1  and R 2  may combine each other together with the adjacent nitrogen atom to form optionally substituted saturated heterocycle; 
     the group X is optionally substituted alkyl, optionally substituted piperidinyl, optionally substituted pyrrolidinyl, optionally substituted arylalkyl, optionally substituted heteroarylalkyl, optionally substituted piperidinylalkyl or optionally substituted pyrrolidinylalkyl, wherein the substituent is hydroxyl, oxo, halogen atom, cyano, nitro, alkyl, alkoxy, amino which may be optionally substituted by alkyl or arylalkyl, methylenedioxy, trihalomethyl, or trihalomethoxy; or a pharmaceutically acceptable salt thereof; 
     [2] The compound of [1] of formula (3): 
     
       
         
         
             
             
         
       
     
     wherein R A  and R B  are each independently optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, or a group of formula: —Rw—Rx—Ry—Rz; 
     Rw is, independently when it exists more than one, optionally substituted alkylene or optionally substituted cycloalkylene; 
     Rx is, independently when it exists more than one, a single bond, oxygen atom, or a group of formula: —S(O) n —, —C(O)—, —NR 3 —, —OC(O)—, —C(O)O—, —CONR 3 —, —NR 3 CO—, —SO 2 NR 3 —, —NR 3 SO 2 — or —NR 3 CONR 4 —; 
     Ry is, independently when it exists more than one, a single bond or optionally substituted alkylene; 
     Rz is, independently when it exists more than one, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted aryl, optionally substituted heteroaryl or optionally substituted heterocycloalkyl; 
     R 3  and R 4  are each independently hydrogen atom or optionally substituted alkyl; 
     n is 0, 1 or 2; 
     R C  is optionally substituted alkyl, optionally substituted cycloalkyl or optionally substituted cycloalkylalkyl; 
     R D  is hydrogen atom, halogen atom, cyano or optionally substituted alkyl; 
     R E  is hydrogen atom or optionally substituted alkyl; 
     A is hydrogen atom, halogen atom, hydroxyl, cyano, or a group of formula: COOR 1 , CONR 1 R 2 , SO 2 NR 1 R 2 , COOR 1 -substituted alkyl, CONR 1 R 2 -substituted alkyl, or SO 2 NR 1 R 2 -substituted alkyl, R 1  and R 2  are each independently hydrogen atom or optionally substituted alkyl, or R 1  and R 2  may combine each other together with the adjacent nitrogen atom to form optionally substituted saturated heterocycle; 
     provided that if both R A  and R B  are selected from the following group X, then A is COOR 1 , CONR 1 R 2 , SO 2 NR 1 R 2 , COOR 1 -substituted alkyl, CONR 1 R 2 -substituted alkyl, or SO 2 NR 1 R 2 -substituted alkyl; 
     the group X is optionally substituted alkyl, optionally substituted piperidinyl, optionally substituted pyrrolidinyl, optionally substituted arylalkyl, optionally substituted heteroarylalkyl, optionally substituted piperidinylalkyl, or optionally substituted pyrrolidinylalkyl, wherein the substituent is hydroxyl, oxo, halogen atom, cyano, nitro, alkyl, alkoxy, amino which may be optionally substituted by alkyl or arylalkyl, methylenedioxy, trihalomethyl, or trihalomethoxy; or a pharmaceutically acceptable salt thereof; 
     [3] The compound of [2], wherein R C  is optionally substituted alkyl, R D  is hydrogen atom, halogen atom or optionally substituted alkyl, R E  is hydrogen atom, A is halogen atom, hydroxyl, cyano, or a group of formula: COOR 1 , CONR 1 R 2 , SO 2 NR 1 R 2 , COOR 1 -substituted alkyl, CONR 1 R 2 -substituted alkyl or SO 2 NR 1 R 2 -substituted alkyl, R 1  and R 2  are each independently hydrogen atom or optionally substituted alkyl, or R 1  and R 2  may combine each other together with the adjacent nitrogen atom to form optionally substituted saturated heterocycle, or a pharmaceutically acceptable salt thereof; 
     [4] The compound of either [2] or [3], wherein R A  and R B  are each independently optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl or optionally substituted heterocycloalkyl, A is a group of formula: COOR 1 , CONR 1 R 2  or SO 2 NR 1 R 2 , R 1  and R 2  are each independently hydrogen atom or optionally substituted alkyl, R A  is optionally substituted cycloalkyl or optionally substituted cycloalkylalkyl, R B  is optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, or a group of formula: —Rw— Rx—Ry—Rz wherein Rw, Rx, Ry and Rz are the same as defined in [2]; or R A  is optionally substituted alkyl, R B  is a group of formula: —Rw—Rx—Ry—Rz wherein Rw, Rx, Ry and Rz are the same as defined in [2], or a pharmaceutically acceptable salt thereof; 
     [5] The compound of any one of [2] to [4], wherein R A  and R B  are each independently optionally substituted alkyl, optionally substituted cycloalkyl or optionally substituted cycloalkylalkyl, 
     A is a group of formula: COOR 1 , CONR 1 R 2  or SO 2 NR 1 R 2 , R 1  and R 2  are each independently hydrogen atom or optionally substituted alkyl, or a pharmaceutically acceptable salt thereof; 
     [6] The compound of either [4] or [5], wherein A is a group of formula: CONR 1 R 2 , R 1  and R 2  are each independently hydrogen atom or alkyl which may be optionally substituted by hydroxyl, alkoxy, benzenesulfonyl or pyridyl, or a pharmaceutically acceptable salt thereof; 
     [7] The compound of [6], wherein A and nitrogen atom on which adamantyl group is substituted are arranged in E-configuration, or a pharmaceutically acceptable salt thereof; 
     [8] The compound of any one of [2] to [4], wherein R A  is optionally substituted cycloalkyl or optionally substituted cycloalkylalkyl, R B  is optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, or a group of formula: —Rw—Rx—Ry—Rz wherein Rw, Rx, Ry and Rz are the same as defined in [2], or a pharmaceutically acceptable salt thereof; 
     [9] The compound of [8], wherein R B  is optionally substituted alkyl, optionally substituted heterocycloalkyl, or a group of formula: —Rw—Rx—Ry—Rz wherein Rw is optionally substituted alkylene, 
     Rx is a single bond, oxygen atom, or a group of formula: —S(O) n —, Ry is a single bond, Rz is optionally substituted aryl or optionally substituted heterocycloalkyl, or a pharmaceutically acceptable salt thereof; 
     [10] The compound of any one of [2] to [4], wherein R A  is optionally substituted alkyl, R B  is a group of formula: —Rw—Rx—Ry—Rz wherein Rw, Rx, Ry and Rz are the same as defined in [2], or a pharmaceutically acceptable salt thereof; 
     [11] The compound of [10], wherein Rx is a group of formula: —S(O) n —, —C(O)—, —NR 3 —, —OC(O)—, —C(O)O—, —CONR 3 —, —NR 3 CO—, —SO 2 NR 3 —, —NR 3 SO 2 — or —NR 3 CONR 4 —, R 3  and R 4  are each independently hydrogen atom or optionally substituted alkyl, n is 0, 1 or 2, or a pharmaceutically acceptable salt thereof; 
     [12] The compound of [11], wherein Rw is optionally substituted alkylene, Rx is a group of formula: —S(O) n —, Ry is a single bond, Rz is optionally substituted alkyl, or a pharmaceutically acceptable salt thereof; 
     [13] The compound of [10], wherein Rx is oxygen atom, Rz is optionally substituted cycloalkyl, optionally substituted aryl, optionally substituted heteroaryl or optionally substituted heterocycloalkyl, or a pharmaceutically acceptable salt thereof; 
     [14] The compound of [13], wherein Rw is optionally substituted alkylene, Ry is a single bond, Rz is optionally substituted aryl or optionally substituted heterocycloalkyl, or a pharmaceutically acceptable salt thereof; 
     [15] The compound of [10], wherein Rx is a single bond, Rz is optionally substituted cycloalkyl or optionally substituted heterocycloalkyl, or a pharmaceutically acceptable salt thereof; 
     [16] The compound of [15], wherein Rw is optionally substituted alkylene, Ry is a single bond, Rz is optionally substituted cycloalkyl or optionally substituted heterocycloalkyl, or a pharmaceutically acceptable salt thereof; 
     [17] The compound of [10], wherein Rx is a single bond, Rz is substituted aryl, substituted heteroaryl or substituted heterocycloalkyl, in which the substituent is —COR 5 , —S(O) n R 5 , —NR 7a COR 5 , —SO 2 NR 7a R 7b , —NR 7a CONR 7b R 5 , —OR 6  or —(CH 2 ) m R 6 , R 5  is alkyl, cycloalkyl, aryl, heteroaryl or heterocycloalkyl, R 6  is cycloalkyl, aryl, heteroaryl or heterocycloalkyl, the alkyl, cycloalkyl, aryl, heteroaryl and heterocycloalkyl groups in R 5  and R 6  may be further optionally substituted by halogen cycloalkylsulfonyl, alkoxyalkoxy, hydroxyalkoxy, cycloalkyloxyalkyl, cycloalkyloxy, haloalkoxyalkyl, hydroxyalkyl, alkoxyalkyl, NR 8a R 8b -substituted alkyl, alkylsulfonylalkyl, cyanoalkyl, cycloalkylalkyl, cycloalkylsulfonylalkyl, alkoxyalkoxyalkyl, hydroxyalkoxyalkyl or nitrogen-containing saturated heterocycle, R 7a , R 7b , R 8a  and R 8b  are each independently hydrogen atom or alkyl, n and m are each independently 0, 1 or 2, or a pharmaceutically acceptable salt thereof; 
     [18] The compound of [17], wherein Rw is optionally substituted alkylene, Ry is a single bond, Rz is substituted aryl or substituted heterocycloalkyl, in which the substituent is —COR 5  or —S(O) n R 5 , or a pharmaceutically acceptable salt thereof; [19] The compound of [10], wherein Rw is optionally substituted cycloalkylene, Rx is a single bond, Ry is a single bond, Rz is optionally substituted aryl, or a pharmaceutically acceptable salt thereof; 
     [20] The compound of [2], wherein R A  is tetrahydropyranyl, R B  is alkyl or cycloalkyl, or a pharmaceutically acceptable salt thereof; 
     [21] The compound of [2] of formula (4): 
     
       
         
         
             
             
         
       
     
     wherein p is 0, 1 or 2, q is 1 or 2, B 1  is a single bond, carbonyl or sulfonyl, B 2  is optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted alkylamino, optionally substituted dialkylamino, optionally substituted cycloalkylamino, optionally substituted heterocycloalkylamino, optionally substituted arylamino or optionally substituted heteroarylamino, provided that B 1  is a single bond, then B 2  is optionally substituted aryl or optionally substituted heteroaryl, or a pharmaceutically acceptable salt thereof; 
     [22] The compound of [21], wherein B 1  is a single bond, B 2  is optionally substituted aryl or optionally substituted heteroaryl, or a pharmaceutically acceptable salt thereof; 
     [23] The compound of [22], wherein B 2  is optionally substituted aryl, or a pharmaceutically acceptable salt thereof; 
     [24] The compound of [22], wherein B 2  is optionally substituted heteroaryl, or a pharmaceutically acceptable salt thereof; 
     [25] The compound of [24], wherein B 2  is optionally substituted pyridyl, or a pharmaceutically acceptable salt thereof; 
     [26] The compound of [21], wherein B 1  is carbonyl, B 2  is optionally substituted aryl, optionally substituted alkyl, optionally substituted cycloalkyl or optionally substituted heteroaryl, or a pharmaceutically acceptable salt thereof; 
     [27] The compound of [26], wherein the optionally substituted alkyl group in B 2  is optionally substituted benzyl, or a pharmaceutically acceptable salt thereof; 
     [28] The compound of [26], wherein the optionally substituted cycloalkyl group in B 2  is cyclopropyl or cyclobutyl substituted by optionally substituted aryl, or a pharmaceutically acceptable salt thereof; 
     [29] The compound of [26], wherein B 2  is optionally substituted aryl, or a pharmaceutically acceptable salt thereof; 
     [30] The compound of [26], wherein B 2  is optionally substituted heteroaryl, or a pharmaceutically acceptable salt thereof; 
     [31] The compound of [26], wherein the optionally substituted heteroaryl group in B 2  is optionally substituted pyridyl, or a pharmaceutically acceptable salt thereof; 
     [32] The compound of [26], wherein B 2  is fluorine-substituted alkyl, or a pharmaceutically acceptable salt thereof; 
     [33] The compound of [21], wherein B 1  is sulfonyl, B 2  is optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, optionally substituted aryl or optionally substituted heteroaryl, or a pharmaceutically acceptable salt thereof; 
     [34] The compound of [33], wherein B 2  is optionally substituted aryl, or a pharmaceutically acceptable salt thereof; 
     [35] The compound of [33], wherein the optionally substituted alkyl group in B 2  is fluorine-substituted alkyl, or a pharmaceutically acceptable salt thereof; 
     [36] The compound of [33], wherein the optionally substituted heteroaryl group in B 2  is optionally substituted pyridyl, or a pharmaceutically acceptable salt thereof; 
     [37] The compound of [33], wherein the optionally substituted alkyl group in B 2  is optionally substituted benzyl, or a pharmaceutically acceptable salt thereof; [38] The compound of [21], wherein B 1  is carbonyl, B 2  is optionally substituted alkylamino, optionally substituted dialkylamino, optionally substituted cycloalkylamino, optionally substituted heterocycloalkylamino, optionally substituted arylamino or optionally substituted heteroarylamino, or a pharmaceutically acceptable salt thereof; 
     [39] The compound of [38], wherein B 2  is optionally substituted arylamino or optionally substituted heteroarylamino, or a pharmaceutically acceptable salt thereof; 
     [40] The compound of [38], wherein B 2  is optionally substituted arylamino, or a pharmaceutically acceptable salt thereof; 
     [41] The compound of [38], wherein the optionally substituted heteroarylamino group in B 2  is optionally substituted pyridylamino, or a pharmaceutically acceptable salt thereof; 
     [42] The compound of [38], wherein the optionally substituted alkylamino group in B 2  is optionally substituted benzylamino, or a pharmaceutically acceptable salt thereof; 
     [43] The compound of any one of [21] to [42], wherein p is 0 and q is 1, or a pharmaceutically acceptable salt thereof; 
     [44] The compound of any one of [21] to [42] of formula (5): 
     
       
         
         
             
             
         
       
     
     or a pharmaceutically acceptable salt thereof; 
     [45] The compound of any one of [21] to [42] of formula (6): 
     
       
         
         
             
             
         
       
     
     or a pharmaceutically acceptable salt thereof; 
     [46] The compound of any one of [21] to [42], wherein p is 1 and q is 2, or a pharmaceutically acceptable salt thereof; 
     [47] The compound of any one of [21] to [42], wherein p is 2 and q is 2, or a pharmaceutically acceptable salt thereof; 
     [48] The compound of any one of [21] to [42], wherein p is 0 and q is 2, or a pharmaceutically acceptable salt thereof; 
     [49] The compound of any one of [21] to [42] of formula (7): 
     
       
         
         
             
             
         
       
     
     or a pharmaceutically acceptable salt thereof; 
     [50] The compound of any one of [21] to [42] of formula (8): 
     
       
         
         
             
             
         
       
     
     or a pharmaceutically acceptable salt thereof; 
     [51] The compound of any one of [21] to [50], wherein R B  is methyl or ethyl, or a pharmaceutically acceptable salt thereof; 
     [52] The compound of any one of [8] to [51], wherein A is hydroxyl, or a pharmaceutically acceptable salt thereof; 
     [53] The compound of any one of [8] to [51], wherein A is carbamoyl, or a pharmaceutically acceptable salt thereof; 
     [54] The compound of any one of [4] to [53], wherein R D  is chlorine atom, fluorine atom or methyl, or a pharmaceutically acceptable salt thereof; 
     [55] The compound of [54], wherein R C  is alkyl, or a pharmaceutically acceptable salt thereof; 
     [56] The compound of [54], wherein R C  is methyl or ethyl, or a pharmaceutically acceptable salt thereof; 
     [57] The compound of [56], wherein R E  is hydrogen atom, or a pharmaceutically acceptable salt thereof; 
     [58] The compound of any one of [4] to [57], wherein A and nitrogen atom on which adamantyl group is substituted are arranged in E-configuration, or a pharmaceutically acceptable salt thereof; 
     [59] A medicament, comprising as the active ingredient the compound of any one of [1] to [58] or a pharmaceutically acceptable salt thereof; 
     [60] A therapeutic agent for type II diabetes, abnormal glucose tolerance, hyperglycemia, insulin resistance, dyslipidemia, hypertension, arteriosclerosis, angiostenosis, obesity, cognitive disorder, dementia, Alzheimer disease, syndrome X, depression, cardiovascular disease or atherosclerosis, comprising as the active ingredient the compound of any one of [1] to [58] or a pharmaceutically acceptable salt thereof; 
     [61] A therapeutic agent for diabetes, insulin resistance or type II diabetes, comprising as the active ingredient the compound of any one of [1] to [58] or a pharmaceutically acceptable salt thereof; 
     [62] A therapeutic agent for arteriosclerosis or atherosclerosis, comprising as the active ingredient the compound of any one of [1] to [58] or a pharmaceutically acceptable salt thereof; 
     [63] A therapeutic agent for syndrome X, comprising as the active ingredient the compound of any one of [1] to [58] or a pharmaceutically acceptable salt thereof; 
     [64] A therapeutic agent for obesity, comprising as the active ingredient the compound of any one of [1] to [58] or a pharmaceutically acceptable salt thereof; 
     [65] A therapeutic agent for cognitive disorder, dementia, Alzheimer disease or depression, comprising as the active ingredient the compound of any one of [1] to [58] or a pharmaceutically acceptable salt thereof; 
     [66] A therapeutic agent for dyslipidemia, comprising as the active ingredient the compound of any one of [1] to [58] or a pharmaceutically acceptable salt thereof; or 
     [67] A therapeutic agent for hypertension, comprising as the active ingredient the compound of any one of [1] to [58] or a pharmaceutically acceptable salt thereof. 
     The invention also relates to the following embodiments: 
     [68] A compound of formula (1): 
     
       
         
         
             
             
         
       
     
     wherein R A  and R B  are each independently optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, or a group of formula: —Rw—Rx—Ry—Rz; 
     Rw is, independently when it exists more than one, optionally substituted alkylene; 
     Rx is, independently when it exists more than one, a single bond, oxygen atom, or a group of formula: —S(O) n —, —C(O)—, —NR 3 —, —OC(O)—, —C(O)O—, —CONR 3 —, —NR 3 CO—, —SO 2 NR 3 —, —NR 3 SO 2 — or —NR 3 CONR 4 —; 
     Ry is, independently when it exists more than one, a single bond or optionally substituted alkylene; 
     Rz is, independently when it exists more than one, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted aryl, optionally substituted heteroaryl or optionally substituted heterocycloalkyl; 
     R 3  and R 4  are each independently hydrogen atom or optionally substituted alkyl; 
     n is 0, 1 or 2; 
     R C  is optionally substituted alkyl, optionally substituted cycloalkyl or optionally substituted cycloalkylalkyl; 
     R D  is hydrogen atom, halogen atom, cyano, optionally substituted alkyl or optionally substituted cycloalkyl; 
     R E  is hydrogen atom or optionally substituted alkyl; 
     R F  is a group selected from the following formulae (G1): 
     
       
         
         
             
             
         
       
     
     wherein one of hydrogen atoms is a bond, which may be optionally substituted; 
     provided that if both R A  and R B  are selected from the following group X, then R F  is a group of the following formula (2): 
     
       
         
         
             
             
         
       
     
     A 1  is COOR 1 , CONR 1 R 2 , SO 2 NR 1 R 2 , COOR 1 -substituted alkyl, CONR 1 R 2 -substituted alkyl, or SO 2 NR 1 R 2 -substituted alkyl, R 1  and R 2  are each independently hydrogen atom or optionally substituted alkyl, or R 1  and R 2  may combine each other together with the adjacent nitrogen atom to form an optionally substituted saturated heterocycle; 
     the group X is optionally substituted alkyl, optionally substituted piperidinyl, optionally substituted pyrrolidinyl, optionally substituted arylalkyl, optionally substituted heteroarylalkyl, optionally substituted piperidinylalkyl or optionally substituted pyrrolidinylalkyl, wherein the substituent is hydroxyl, oxo, halogen atom, cyano, nitro, alkyl, alkoxy, amino which may be optionally substituted by alkyl or arylalkyl, methylenedioxy, trihalomethyl, or trihalomethoxy; or a pharmaceutically acceptable salt thereof; 
     [69] The compound of [68] of formula (3): 
     
       
         
         
             
             
         
       
     
     wherein R A  and R B  are each independently optionally substituted alkyl, optionally substituted cycloalkyl, or a group of formula: —Rw—Rx—Ry—Rz; 
     Rw is, independently when it exists more than one, optionally substituted alkylene; 
     Rx is, independently when it exists more than one, a single bond, oxygen atom, or a group of formula: —S(O) n —, —C(O)—, —NR 3 —, —OC(O)—, —C(O)O—, —CONR 3 —, —NR 3 CO—, —SO 2 NR 3 —, —NR 3 SO 2 — or —NR 3 CONR 4 —; 
     Ry is, independently when it exists more than one, a single bond or optionally substituted alkylene; 
     Rz is, independently when it exists more than one, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted aryl, optionally substituted heteroaryl or optionally substituted heterocycloalkyl; 
     R 3  and R 4  are each independently hydrogen atom or optionally substituted alkyl; 
     n is 0, 1 or 2; 
     R C  is optionally substituted alkyl, optionally substituted cycloalkyl or optionally substituted cycloalkylalkyl; 
     R D  is hydrogen atom, halogen atom, cyano, optionally substituted alkyl or optionally substituted cycloalkyl; 
     R E  is hydrogen atom or optionally substituted alkyl; 
     A is hydrogen atom, halogen atom, hydroxyl, cyano, or a group of formula: COOR 1 , CONR 1 R 2 , SO 2 NR 1 R 2 , COOR 1 -substituted alkyl, CONR 1 R 2 -substituted alkyl, or SO 2 NR 1 R 2 -substituted alkyl, R 1  and R 2  are each independently hydrogen atom or optionally substituted alkyl, or R 1  and R 2  may combine each other together with the adjacent nitrogen atom to form optionally substituted saturated heterocycle; 
     provided that if both R A  and R B  are selected from the following group X, then A is COOR 1 , CONR 1 R 2 , SO 2 NR 1 R 2 , COOR 1 -substituted alkyl, CONR 1 R 2 -substituted alkyl, or SO 2 NR 1 R 2 -substituted alkyl; 
     the group X is optionally substituted alkyl, optionally substituted piperidinyl, optionally substituted pyrrolidinyl, optionally substituted arylalkyl, optionally substituted heteroarylalkyl, optionally substituted piperidinylalkyl, or optionally substituted pyrrolidinylalkyl, wherein the substituent is hydroxyl, oxo, halogen atom, cyano, nitro, alkyl, alkoxy, amino which may be optionally substituted by alkyl or arylalkyl, methylenedioxy, trihalomethyl, or trihalomethoxy; or a pharmaceutically acceptable salt thereof; 
     [70] The compound of [69], wherein R C  is optionally substituted alkyl, R D  is hydrogen atom, halogen atom or optionally substituted alkyl, R E  is hydrogen atom, A is halogen atom, hydroxyl, cyano, or a group of formula: COOR 1 , CONR 1 R 2 , SO 2 NR 1 R 2 , COOR 1 -substituted alkyl, CONR 1 R 2 -substituted alkyl or SO 2 NR 1 R 2 -substituted alkyl, R 1  and R 2  are each independently hydrogen atom or optionally substituted alkyl, or R 1  and R 2  may combine each other together with the adjacent nitrogen atom to form an optionally substituted saturated heterocycle, or a pharmaceutically acceptable salt thereof; 
     [71] The compound of either [69] or [70], wherein R A  and R B  are each independently optionally substituted alkyl, optionally substituted cycloalkyl or optionally substituted cycloalkylalkyl, A is a group of formula: COOR 1 , CONR 1 R 2  or SO 2 NR 1 R 2 , R 1  and R 2  are each independently hydrogen atom or optionally substituted alkyl, or a pharmaceutically acceptable salt thereof; 
     [72] The compound of [71], wherein A is a group of formula: CONR 1 R 2 , R 1  and R 2  are each independently hydrogen atom, or a pharmaceutically acceptable salt thereof; 
     [73] The compound of [72], wherein A and nitrogen atom on which adamantyl group is substituted are arranged in E-configuration, or a pharmaceutically acceptable salt thereof; 
     [74] The compound of either [69] or [70], wherein R A  is optionally substituted cycloalkyl or optionally substituted cycloalkylalkyl, R B  is optionally substituted alkyl, optionally substituted cycloalkyl, or a group of formula: —Rw—Rx—Ry—Rz wherein Rw, Rx, Ry and Rz are the same as defined in [69], or a pharmaceutically acceptable salt thereof; 
     [75] The compound of either [69] or [70], wherein R A  is optionally substituted alkyl, R B  is a group of formula: —Rw—Rx—Ry—Rz wherein Rw, Rx, Ry and Rz are the same as defined in [69], or a pharmaceutically acceptable salt thereof; 
     [76] The compound of [75], wherein Rx is a group of formula: —S(O) n —, —C(O)—, —NR 3 —, —OC(O)—, —C(O)O—, —CONR 3 —, —NR 3 CO—, —SO 2 NR 3 —, —NR 3 SO 2 — or —NR 3 CONR 4 —, R 3  and R 4  are each independently hydrogen atom or optionally substituted alkyl, n is 0, 1 or 2, or a pharmaceutically acceptable salt thereof; 
     [77] The compound of [75], wherein Rx is oxygen atom, Rz is optionally substituted cycloalkyl, optionally substituted aryl, optionally substituted heteroaryl or optionally substituted heterocycloalkyl, or a pharmaceutically acceptable salt thereof; 
     [78] The compound of [75], wherein Rx is a bond, Rz is optionally substituted cycloalkyl or optionally substituted heterocycloalkyl, or a pharmaceutically acceptable salt thereof; 
     [79] The compound of [75], wherein Rx is a bond, Rz is substituted aryl, substituted heteroaryl or substituted heterocycloalkyl, in which the substituent is —COR 5 , —S(O) n R 5 , —NR 7a COR 5 , —SO 2 NR 7a R 7b , —NR 7a CONR 7b R 5 , —OR 6  or —(CH 2 ) m R 6 , R 5  is alkyl, cycloalkyl, aryl, heteroaryl or heterocycloalkyl, R 6  is cycloalkyl, aryl, heteroaryl or heterocycloalkyl, the alkyl, cycloalkyl, aryl, heteroaryl and heterocycloalkyl groups in R 5  and R 6  may be further optionally substituted by halogen atom, haloalkyl, haloalkoxy, alkyl, hydroxyl, alkoxy, —NR 8a R 8b , alkylsulfonyl, cyano, cycloalkyl, cycloalkylsulfonyl, alkoxyalkoxy, hydroxyalkoxy, cycloalkyloxyalkyl, cycloalkyloxy, haloalkoxyalkyl, hydroxyalkyl, alkoxyalkyl, NR 8a R 8b -substituted alkyl, alkylsulfonylalkyl, cyanoalkyl, cycloalkylalkyl, cycloalkylsulfonylalkyl, alkoxyalkoxyalkyl, hydroxyalkoxyalkyl or nitrogen-containing saturated heterocycle, R 7a , R 7b , R 8a  and R 8b  are each independently hydrogen atom or alkyl, n and m are each independently 0, 1 or 2, or a pharmaceutically acceptable salt thereof; 
     [80] The compound of any one of [74] to [79], wherein A is hydroxyl, or a pharmaceutically acceptable salt thereof; 
     [81] The compound of any one of [74] to [79], wherein A is carbamoyl, or a pharmaceutically acceptable salt thereof; 
     [82] The compound of either [80] or [81], wherein R D  is chlorine atom, or a pharmaceutically acceptable salt thereof; 
     [83] The compound of [82], wherein R C  is alkyl, or a pharmaceutically acceptable salt thereof; 
     [84] The compound of [82], wherein R C  is methyl or ethyl, or a pharmaceutically acceptable salt thereof; 
     [85] The compound of any one of [80] to [84], wherein A and nitrogen atom on which adamantyl group is substituted are arranged in E-configuration, or a pharmaceutically acceptable salt thereof; 
     [86] A medicament, comprising as the active ingredient the compound of any one of [68] to [85] or a pharmaceutically acceptable salt thereof; 
     [87] A therapeutic agent for type II diabetes, abnormal glucose tolerance, hyperglycemia, insulin resistance, dyslipidemia, hypertension, arteriosclerosis, angiostenosis, obesity, cognitive disorder, dementia, Alzheimer disease, syndrome X, depression, cardiovascular disease or atherosclerosis, comprising as the active ingredient the compound of any one of [68] to [85] or a pharmaceutically acceptable salt thereof; 
     [88] A therapeutic agent for diabetes, insulin resistance or type II diabetes, comprising as the active ingredient the compound of any one of [68] to [85] or a pharmaceutically acceptable salt thereof; 
     [89] A therapeutic agent for arteriosclerosis or atherosclerosis, comprising as the active ingredient the compound of any one of [68] to [85] or a pharmaceutically acceptable salt thereof; 
     [90] A therapeutic agent for syndrome X, comprising as the active ingredient the compound of any one of [68] to [85] or a pharmaceutically acceptable salt thereof; 
     [91] A therapeutic agent for obesity, comprising as the active ingredient the compound of any one of [68] to [85] or a pharmaceutically acceptable salt thereof; 
     [92] A therapeutic agent for cognitive disorder, dementia, Alzheimer disease or depression, comprising as the active ingredient the compound of any one of [68] to [85] or a pharmaceutically acceptable salt thereof; 
     [93] A therapeutic agent for dyslipidemia, comprising as the active ingredient the compound of any one of [68] to [85] or a pharmaceutically acceptable salt thereof; or 
     [94] A therapeutic agent for hypertension, comprising as the active ingredient the compound of any one of [68] to [85] or a pharmaceutically acceptable salt thereof. 
     ADVANTAGEOUS EFFECT OF INVENTION 
     The compound of the invention is useful as a therapeutic and/or preventive agent for diseases including type II diabetes, abnormal glucose tolerance, hyperglycemia, insulin resistance, hypo-HDL-emia, hyper-LDL-emia, dyslipidemia, hyperlipidemia, hypertriglyceridemia, hypercholesterolemia, hypertension, arteriosclerosis, angiostenosis, atherosclerosis, obesity, cognitive disorder, glaucoma, retinopathy, dementia, Alzheimer disease, osteoporosis, immune disorder, syndrome X, depression, cardiovascular disease, neurodegenerative disease, etc. 
    
    
     BEST MODE FOR CARRYING OUT THE INVENTION 
     The invention is illustrated in more detail as below. 
     The number of substituents of “optionally substituted” or “substituted” groups herein is one or more without limitation if substitution is acceptable. Each definition of each group is applied to any groups which constitute a part of other groups or a substituent thereof, unless it is specified. 
     The term “halogen atom” includes fluorine atom, chlorine atom, bromine atom and iodine atom, preferably fluorine atom or chlorine atom. 
     The term “alkyl” includes C 1 -C 5  straight- and branched-chain alkyl, specifically methyl, ethyl, propyl, 1-methylethyl, butyl, 1-methylpropyl, 2-methylpropyl, 1,1-dimethylethyl, pentyl, 2,2-dimethylpropyl, etc. 
     The alkyl moiety of cycloalkylalkyl, arylalkyl, heteroarylalkyl, alkylsulfonyl, etc. includes the same as defined in the above alkyl. 
     The term “alkoxy” includes C 1 -C 5  alkoxy, specifically methoxy, ethoxy, propoxy, 1-methylethoxy, butoxy, 1-methylpropoxy, 2-methylpropoxy, 1,1-dimethylethoxy, pentyloxy, 2,2-dimethylpropoxy, etc. 
     The alkoxy moiety of alkoxyalkyl, etc. includes the same as defined in the above alkoxy. 
     The term “trihalomethyl” includes methyl substituted by three halogen atoms. 
     The term “trihalomethoxy” includes methoxy substituted by three halogen atoms. 
     The term “haloalkyl” includes alkyl substituted by halogen atom. 
     The term “haloalkoxy” includes alkoxy substituted by halogen atom. The term “alkylene” includes C 1 -C 5  straight- and branched-chain alkylene, specifically methylene, ethylene, trimethylene, tetramethylene, etc. 
     The term “cycloalkyl” includes C 3 -C 8  cycloalkyl, specifically cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl or cyclooctyl. 
     The cycloalkyl may have any double bonds in any substituent positions. 
     The cycloalkyl moiety of cycloalkyloxy, cycloalkylalkyl, etc. includes the same as defined in the above cycloalkyl. 
     The cycloalkyl includes any groups which are allowed to be fused with aryl or heteroaryl, for example any groups of the following formulae (B1): 
     
       
         
         
             
             
         
       
     
     wherein any hydrogen atom of non-aromatic ring moiety is replaced with a bond. 
     The term “cycloalkylene” includes C 3 -C 8  cycloalkane, or any groups of the above formulae (B1) wherein two hydrogen atoms of non-aromatic ring moieties are replaced with bonds. The C 3 -C 8  cycloalkane specifically includes cyclopropane, cyclobutane, cyclopentane, cyclohexane, cycloheptane or cyclooctane. 
     The term “aryl” includes C 6 -C 10  aryl, specifically phenyl, 1-naphthyl, 2-naphthyl or indenyl. A preferable aryl includes phenyl. 
     The term “heteroaryl” includes 5 to 10-membered mono and multi-cyclic group containing one or more (e.g., 1 to 4) heteroatoms selected from nitrogen atom, sulfur atom or oxygen atom. Specifically, it includes furyl, thienyl, pyrrolyl, azepinyl, pyrazolyl, imidazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, 1,2,4-thiadiazolyl, 1,2,4-oxadiazolyl, 1,3,4-oxadiazolyl, 1,2,4-triazolyl, 1,2,3-triazolyl, pyranyl, pyridyl, pyridazinyl, pyrimidyl, pyrazinyl, indolyl, benzothienyl, benzofuryl, quinolyl, isoquinolyl, quinazolyl, quinoxalinyl, benzoxazolyl, benzothiazolyl, pyrazyl, triazinyl, tetrazolyl, imidazo[1,2-a]pyridyl, dibenzofuranyl, benzimidazolyl, cinnolyl, indazolyl, naphthyridyl, quinolonyl or isoquinolonyl. 5 to 6-membered cyclic group containing 1 to 3 heteroatoms selected from nitrogen atom, sulfur atom or oxygen atom is preferable, specifically pyridyl, pyrazinyl, thienyl, oxazolyl, 1,2,4-oxadiazolyl or pyridazinyl. 
     The aryl moiety of aryloxy, etc. includes the same as defined in the above aryl. The heteroaryl moiety of heteroaryloxy includes the same as defined in the above aryl. 
     The term “heterocycloalkyl” includes 5 to 6-membered ring heterocycloalkyl containing one or more (e.g., 1 to 3) heteroatoms selected from nitrogen atom, sulfur atom or oxygen atom, specifically pyrrolidinyl, imidazolidinyl, piperidinyl, morpholinyl, thiomorpholinyl, dioxothiomorpholinyl, hexamethyleneiminyl, oxazolidinyl, thiazolidinyl, imidazolidinyl, oxoimidazolidinyl, dioxoimidazolidinyl, oxooxazolidinyl, dioxooxazolidinyl, dioxothiazolidinyl, tetrahydropyridinyl, tetrahydrofuranyl or tetrahydropyranyl. 
     The term “heterocycloalkyl” also includes any groups wherein any hydrogen atom of thiomorpholin-1-oxide, morpholin-3-one, thiomorpholin-3-one, piperidin-4-one, piperidin-3-one, piperazine-2,6-dione, morpholin-2-one, piperazine, piperazin-2-one, piperazine-2,3-dione, piperazine-2,5-dione, tetrahydropyrimidin-2(1H)-one, 1,3-oxazinan-2-one, 1,3-oxazolidine, 1,3-thiazolidine, imidazolidin-2-one, 1,3-oxazolidin-2-one, 2,5-dihydro-1H-pyrrole, imidazolidine-2,4-dione, imidazolidin-4-one, 1,4-diazepane, 1,4-oxazepan, tetrahydro-2H-pyrane, tetrahydro-2H-thiopyrane, tetrahydro-2H-thiopyrane-1-oxide, tetrahydro-2H-thiopyrane-1,1-dioxide, 1,4-diazepan-3-one, 1,4-oxazepan-3-one, aziridine, azetidine, azetidine, pyrrolidine, azepane, azocane, pyrrolidin-2-one, piperidin-2-one, azepan-2-one, azocan-2-one, 1,5-dihydro-2H-pyrrol-2-one, 5,6-dihydropyridin-2(1H)-one, 1,5,6,7-tetrahydro-2H-azepin-2-one, 1,5,6,7-tetrahydro-2H-azepin-2-one, 5,6,7,8-tetrahydroazocin-2(1H)-one, 1,2,3,4-tetrahydropyridine, 1,2,3,6-tetrahydropyridine, 2,3,4,7-tetrahydro-1H-azepine, 1,2,3,4,5,8-hexahydroazocine, tetrahydrofuran, tetrahydrothiophene, 1,2-oxathiolane, etc. are replaced with bonds. 
     A preferable heterocycloalkyl includes pyrrolidyl, piperidyl, morpholinyl, thiomorpholinyl, dioxothiomorpholinyl, oxazolidinyl, more preferably pyrrolidyl or piperidyl. 
     The term “heterocycloalkyl” also includes any groups fused with aryl or heteroaryl, for example any groups wherein any hydrogen atoms of non-aromatic cyclic moieties of the following formulae (B2) or (B3) are replaced with bonds. 
     The term “nitrogen-containing saturated heterocycle” includes 5 to 6-membered nitrogen-containing saturated heterocycle, etc. which contain 1 to 2 nitrogen atoms and may contain oxygen atoms or sulfur atoms, specifically pyrrolidinyl, imidazolidinyl, piperidinyl, morpholinyl, thiomorpholinyl, dioxothiomorpholinyl, hexamethyleneiminyl, oxazolidinyl, thiazolidinyl, imidazolidinyl, oxoimidazolidinyl, dioxoimidazolidinyl, oxooxazolidinyl, dioxooxazolidinyl, dioxothiazolidinyl or tetrahydropyridinyl. A preferable one includes pyrrolidinyl, piperidinyl, thiomorpholinyl, dioxothiomorpholinyl, morpholinyl. 
     The term “aralkyl” includes C 7 -C 12  aralkyl wherein alkyl is substituted by aryl, specifically benzyl, 2-phenylethyl or 1-naphthylmethyl. 
     The aralkyl moiety of aralkyloxy includes the same as defined in the above aralkyl. 
     The substituents of “substituted alkyl”, “substituted alkoxy” and “substituted cycloalkyl” include halogen atom, hydroxyl, nitro, cyano, —OR 10 , —OCOR 10 , —COR 10 , —COOR 10 , C 3 -C 6  cycloalkyl, amino, carboxy, carbamoyl, —NHR 10 , —NR 10 R 11 , —NR 12 COR 10 , —CONR 10 R 11 , —NR 12 CONR 10 R 11 , —NR 12 SO 2 R 10  or —SO 2 R 10  (wherein R 10  and R 11  are each independently cycloalkyl, C 1 -C 4  alkyl, C 6 -C 10  aryl, heteroaryl or C 7 -C 12  aralkyl, which may further substituted by hydroxyl, halogen atom, C 1 -C 4  alkoxy, cycloalkoxy, C 1 -C 4  alkyl, cycloalkyl, haloalkyl, haloalkoxy, amino, C 1 -C 4  alkylamino or C 1 -C 4  dialkylamino, or R 10  and R 11  may combine each other together with the adjacent nitrogen atom to form an optionally substituted saturated heterocycle; R 12  is hydrogen atom or alkyl). A preferable one includes halogen atom, hydroxyl, alkyl, haloalkoxy, alkylsulfonyl and alkoxy. More preferable one includes halogen atom and alkoxy. 
     The substituent of “substituted cycloalkyl” also includes alkyl which may be optionally substituted by aryl, alkoxy or halogen atom. 
     The substituent of the substituted cycloalkyl also includes optionally substituted aryl and optionally substituted heteroaryl. 
     The substituents of “substituted aryl” and “substituted heteroaryl” include halogen atom, hydroxyl, nitro, cyano, nitrogen-containing saturated heterocycle, cycloalkyl, cycloalkyloxy, C 1 -C 4  alkyl (wherein alkyl may be substituted by halogen atom, hydroxyl, amino, cycloalkyloxy, haloalkoxy, alkoxyalkoxy, cycloalkyl, alkoxy, alkylsulfonyl, cycloalkylsulfonyl, hydroxyalkoxy, etc.), C 1 -C 4  alkoxy (wherein alkoxy may be substituted by halogen atom, hydroxyl, alkoxy, etc.), —COR 10 , —OCOR 10 , —COOR 10 , carboxy, amino, —NHR 10 , —NR 10 R 11 , —NHCOR 10 , —CONH 2 , —CONHR 10 , —CONR 10 R 11 , —SO 2 NH 2 , —SO 2 NHR 10 , —SO 2 NR 10 R 11 , C 6 -C 10  aryl, C 6 -C 10  aryloxy, C 7 -C 12  aralkyloxy (wherein aryl, aryloxy or aralkyloxy may be substituted by hydroxyl, halogen atom, C 1 -C 4  alkoxy, etc.), —SO 2 R 10 , cycloalkylsulfonyl (wherein R 10  and R 11  are the same as defined above), etc. 
     A preferable substituent includes nitrogen-containing saturated heterocycle, alkylsulfonyl, halogen atom, hydroxyl, alkyl (which may be optionally substituted by alkoxy or halogen atom), or alkoxy (which may be optionally substituted by alkoxy or halogen atom), etc. More preferable one includes halogen atom, alkylsulfonyl, alkyl (which may be optionally substituted by alkoxy or halogen atom), or alkoxy (which may be optionally substituted by halogen atom). 
     The substituent of the substituted aryl also includes C 1 -C 3  alkylenedioxy such as methylenedioxy or ethylenedioxy. 
     The term “substituted aryl” includes any groups fused with cycloalkyl and cycloheteroalkyl, for example any groups of the above formulae (B1) and the following formulae (B2): 
     
       
         
         
             
             
         
       
     
     wherein any hydrogen atoms of aromatic ring moieties are replaced with bonds, which may be further optionally substituted by the above listed substituents. 
     The term “substituted heteroaryl” includes any groups fused with cycloalkyl and cycloheteroalkyl, for example any groups of the following formula (B3): 
     
       
         
         
             
             
         
       
     
     wherein any hydrogen atoms of aromatic ring moiety are replaced with bonds, which may be further optionally substituted by the above listed substituents. 
     The substituents of aryl and heteroaryl moieties of “substituted aralkyl” and “substituted heteroarylalkyl” include any groups listed as the substituents of “substituted aryl” and “substituted heteroaryl”. 
     The substituent of alkyl moiety of “substituted aralkyl” includes any groups listed as the substituents of “substituted alkyl”. 
     The substituent of “substituted heterocycloalkyl” or “substituted nitrogen-containing saturated heterocycle” includes C 1 -C 4  alkyl (which may be optionally substituted by aryl, alkoxy or halogen atom), optionally substituted aryl, optionally substituted heteroaryl, —OR 10 , —OCOR 10 , —COR 10 , —COOR 1 , C 3 -C 6  cycloalkyl, amino, carboxy, carbamoyl, —NHR 10 , —NR 10 R 11 , NR 12 COR 10 , —CONR 10 R 11 , —NR 12 COR 10 R 11 , —NR 12 SO 2 R 10  or —SO 2 R 10  (wherein R 10  and R 11  are each independently cycloalkyl, C 1 -C 4  alkyl, C 6 -C 10  aryl, heteroaryl or C 7 -C 12  aralkyl, which may be further optionally substituted by hydroxyl, halogen atom, C 1 -C 4  alkoxy, cycloalkoxy, C 1 -C 4  alkyl, cycloalkyl, haloalkyl, haloalkoxy, aryl, heteroaryl, amino, C 1 -C 4  alkylamino or C 1 -C 4  dialkylamino, or R 10  and R 11  may combine each other together with the adjacent nitrogen atom to form an optionally substituted saturated heterocycle; R 12  is hydrogen atom or alkyl). A preferable substituent includes alkyl, C 6 -C 10  aryl, heteroaryl, —COR 10 , —CON 10 R 11  or —SO 2 R 10 . 
     A preferable substituent of alkyl of R 5  or R 6  includes halogen atom, hydroxyl or alkoxy. 
     A preferable substituent of cycloalkyl, aryl, heteroaryl and heterocycloalkyl of R 5  or R 6  includes halogen atom, hydroxyl, alkyl (which may be optionally substituted by hydroxyl, alkoxy or halogen atom), and alkoxy (which may be optionally substituted by hydroxyl, alkoxy or halogen atom). 
     A preferable substituent of R 1  or R 2  includes halogen atom, hydroxyl, alkoxy, arylsulfonyl or pyridyl. 
     Alkylamino means amino group substituted by alkyl group. 
     Dialkylamino means amino group substituted by the same or different two alkyl groups. 
     Cycloalkylamino means amino group substituted by cycloalkyl group as well as cyclic amino group including pyrrolidino or piperidino. 
     Heterocycloalkylamino means amino group substituted by heterocycloalkyl group and also includes cyclic amino group including morpholino or thiomorpholino. 
     Arylamino is amino substituted by aryl group. 
     Heteroarylamino is amino substituted by heteroaryl group. 
     The substituent of “substituted alkylamino”, “substituted dialkylamino”, “substituted cycloalkylamino”, “substituted heterocycloamino”, “substituted arylamino” or “substituted heteroarylamino” includes any groups listed as the substituents of “substituted alkyl”, “substituted dialkyl”, “substituted cycloalkyl”, “substituted heterocycloalkyl”, “substituted aryl” or “substituted heteroaryl”. 
     A group selected from (G2) preferably includes adamantyl. 
     Adamantyl may be optionally substituted, and a preferable substituent position includes a position where A is bonded in the following formula: 
     
       
         
         
             
             
         
       
     
     A group, wherein the substituent A and nitrogen atom, on which the adamantyl group is substituted, are arranged in E-configuration is more preferable. 
     
       
         
         
             
             
         
       
     
     E-Configuration 
     The “pharmaceutically acceptable salt” includes alkali metal salt such as potassium salt or sodium salt, alkaline earth metal salt such as calcium salt or magnesium salt, ammonium salt, a water-soluble amine addition salt such as ammonium salt or N-methylglucamine (meglumine), or a lower alkanolammonium salt of an organic amine; and, for example, hydrochloride, hydrobromide, hydroiodide, nitrate, sulfate, hydrogen sulfate, phosphate, acetate, lactate, citrate, tartrate, hydrogen tartrate, succinate, maleate, fumarate, gluconate, saccharate, benzoate, methanesulfonate, ethanesulfonate, benzenesulfonate, para-toluenesulfonate, or pamoate [1,1′-methylene-bis-(2-hydroxy-3-naphthoate)], etc. 
     A resultant salt form of the inventive compound may be directly purified to give a salt of the inventive compound, or a free form of the inventive compound may be dissolved or suspended in an appropriate organic solvent to form a salt thereof by the addition of an acid or a base in a conventional manner 
     The inventive compound and a pharmaceutically acceptable salt thereof may exist in the form of adducts with water or various solvents which are included in the invention. The invention includes all tautomers, all possible stereoisomers and all crystalline forms of the inventive compound. 
     The inventive compound or a pharmaceutically acceptable salt thereof may be orally or parenterally administered (e.g., intravenous, subcutaneous, or drops, intramuscular injection, subcutaneous injection, internal nasal formulation, eye-drop, suppository, transdermal administration formulation including ointment, cream or lotion, etc.) for medical use. A dosage form for oral administration includes tablet, capsule, pill, granule, powder, solution, syrup and suspension, etc. and a dosage form for parenteral administration includes aqueous or oil preparation for injection, ointment, cream, lotion, aerosol, suppository, patch, etc. 
     The preparation may be formulated by using conventional known techniques and comprise a conventionally acceptable carrier, excipient, binder, stabilizer, lubricant, disintegrant, etc. The preparation for injection may further comprise an acceptable buffer, solubilizing agent, isotonic agent, etc. The preparation may also optionally comprise flavoring agent. 
     The excipient may include an organic excipient including sugar derivative such as lactose, sucrose, glucose, mannitol, sorbitol; starch derivative such as corn starch, potato starch, alpha-starch, dextrin, carboxymethyl starch; cellulose derivative such as crystalline cellulose, low-substituted hydroxypropyl cellulose, hydroxypropyl methylcellulose, carboxymethylcellulose, carboxymethylcellulose calcium, internally-crosslinked carboxymethylcellulose sodium; gum arabic; dextran; pullulan; and an inorganic excipient including silicate derivative such as light anhydrous silicic acid, synthetic aluminum silicate, magnesium aluminometasilicate; phosphate such as calcium phosphate; carbonate such as calcium carbonate; sulfate such as calcium sulfate. 
     The lubricant may include stearic acid, metal stearate such as calcium stearate, magnesium stearate; talc; colloid silica; wax such as VEEGUM®, spermaceti; boric acid; adipic acid; sulfate such as sodium sulfate; glycol; fumaric acid; sodium benzoate; DL-leucine; fatty acid sodium salt; lauryl sulfate such as sodium lauryl sulfate, magnesium lauryl sulfate; silicic acid such as anhydrous silicic acid, silicic acid hydrate; and the above starch derivative, etc. 
     The binder may include polyvinylpyrrolidone, macrogol, and the above substances listed as the excipient. 
     The disintegrant may include the above substances listed as the excipient and chemically modified starch-cellulose such as croscarmellose sodium, sodium carboxymethyl starch or cross-linked polyvinylpyrrolidone. 
     The stabilizer may include paraoxybenzoic acid ester such as methylparaben, propylparaben; alcohol such as chlorobutanol, benzyl alcohol, phenylethyl alcohol; benzalkonium chloride; phenols such as phenol, cresol; thimerosal; dehydroacetic acid; and sorbic acid. 
     The flavoring agent may include conventionally-used sweetener, acidulant, perfume, etc. 
     A tablet for oral administration may comprise an excipient together with various disintegrants as well as granulating binders. A lubricant is often very useful for tablet formulation. The similar type of the solid composition may be used as a bulking agent of a gelatin capsule which may be combined by any ingredients, preferably lactose or milk sugar, or high-molecular-weight polyethyleneglycol. 
     The active ingredient of aqueous suspension and/or elixir for oral administration may be combined with a diluent together with various sweetening agents, flavoring agents, coloring agents or dyes, or if desired, emulsifiers and/or suspending agents. The diluent includes water, ethanol, propylene glycol, glycerin and a mixture thereof. It is conveniently included in feed or drinking water for animal in a concentration of 5-5000 ppm, preferably 25-5000 ppm. 
     A solution of the active ingredient for sterile injection may be usually prepared for parenteral administration (intramuscular, intraperitoneal, subcutaneous and intravenous use). A solution of the inventive compound in sesame oil or peanut oil or aqueous propylene glycol may be used. The aqueous solution should be appropriately adjusted and buffered preferably in more than 8 of pH, if needed, to firstly prepare an isotonic solution of a liquid diluent. The aqueous solution is suitable for intravenous injection. The oil solution is suitable for intra-articular, intramuscular and subcutaneous injections. All solutions may be easily prepared under sterile conditions by using typical formulation techniques known to those skilled in the art. 
     The inventive compound or a pharmaceutically acceptable salt thereof for the intranasal or inhalation administration may be provided in the solution or suspension form squeezed out or released by a patient from a pump spray vessel, or as an aerosol spray from a pressurized vessel or a nebulizer with using an appropriate propellant including dichlorodifluoromethane, trichlorofluoromethane, dichlorotetrafluoroethane or carbon dioxide or using other appropriate gas. A dosage unit in the pressurized aerosol may be determined by a bulb which provides a certain measured amount of the active ingredient. A solution or suspension of the active compound may be contained in the pressurized vessel or nebulizer. 
     A capsule and cartridge for an inhaler or insufflator (e.g., prepared from gelatin) may be formulated to contain the inventive compound and a powder composition of appropriate powder bases including lactose or starch. 
     The inventive compound or a pharmaceutically acceptable salt thereof may be also formulated in a composition for the anus such as a suppository or retension enema comprising conventional suppository bases including cacao butter or other glycerides. 
     A usage of the inventive compound or a pharmaceutically acceptable salt thereof depends on conditions, ages, administration methods, etc., and for example, it is 0.01 mg, preferably 1 mg, as a lower limit and 5000 mg, preferably 500 mg, as a upper limit per day at one time or in several divided doses for adults for oral administration, preferably depending on conditions. It is expected to be effective in 0.01 mg, preferably 0.1 mg, as a lower limit and 1000 mg, preferably 30 mg, as an upper limit per day at one time or in several divided doses for adults for intravenous administration depending on conditions. 
     The inventive compound may be used in combination with a drug, referred to as a combination drug hereinafter, including a therapeutic agent for diabetes or diabetic complication, anti-hyperlipidemia, antihypertensive, anti-obesity agent, diuretic, etc. for the purpose of enhancement of efficacy. The inventive compound may be administered to a subject simultaneously with a combination drug or at intervals without limitation. The inventive compound may be formulated with a combination drug to prepare a drug combination. A dosage of a combination drug may be optionally selected on the basis of clinically acceptable doses. A compounding ratio of the inventive compound and a combination drug may be optionally selected depending on administration subjects, administration routes, intended diseases, conditions and a combination thereof. For example, 0.01-100 parts of a combination drug to 1 part of the inventive compound by weight may be administered for human. 
     The therapeutic agent for diabetes includes insulin formulations (e.g., animal insulin formulations extracted from bovine or swine pancreas; human insulin formulations genetically engineered by using  E. coli  or yeast cells, etc.), insulin resistance improving agents (e.g., pioglitazone or a hydrochloride salt thereof, troglitazone, rosiglitazone or a maleate salt thereof, G1-262570, JTT-501, MCC-555, YM-440, KRP-297, CS-011, etc.), alpha-glucosidase inhibitors (e.g., voglibose, acarbose, miglitol, emiglitate, etc.), biguanides (e.g., metformin, etc.), insulin secretion stimulators (e.g., sulfonylurea agents such as tolbutamide, glibenclamide, gliclazide, chlorpropamide, tolazamide, acetohexamide, glyclopyramide, glimepiride; repaglinide, senaglinide, nateglinide, mitiglinide, etc.), dipeptidyl peptidase-IV (DPP-IV) inhibitors (e.g., sitagliptin or a phosphate salt thereof, vildagliptin, alogliptin or a benzoate salt thereof, denagliptin or a tosylate salt thereof, etc.), GLP-1, GLP-1 analogs (exenatide, liraglutide, SUN-E7001, AVE010, BIM-51077, CJC1131, etc.), protein tyrosine phosphatase inhibitors (e.g., vanadic acid, etc.), β3 agonists (e.g., GW-427353B, N-5984, etc.). 
     The therapeutic agent for diabetic complication includes aldose reductase inhibitors (e.g., tolrestat, epalrestat, zenarestat, zopolrestat, minalrestat, fidarestat, ranirestat, SK-860, CT-112, etc.), neurotrophic factors (e.g., NGF, NT-3, BDNF, etc.), PKC inhibitors (e.g., LY-333531, etc.), AGE inhibitors (e.g., ALT946, pimagedine, piratoxatin, N-phenacylthiazolium bromide (ALT766), etc.), active oxygen removers (e.g., thioctic acid, etc.), cerebral blood-vessel dilators (e.g., tiapride, mexiletine, etc.). The anti-hyperlipidemia includes HMG-CoA reductase inhibitors (e.g., pravastatin, simvastatin, lovastatin, atorvastatin, fluvastatin, pitavastatin or a sodium salt thereof, etc.), squalene synthetase inhibitors, ACAT inhibitors, etc. The antihypertensive includes angiotensin-converting enzyme inhibitors (e.g., captopril, enalapril, alacepril, delapril, lisinopril, imidapril, benazepril, cilazapril, temocapril, trandolapril, etc.), angiotensin II antagonists (e.g., olmesartan, medoxomil, candesartan, cilexetil, losartan, eprosartan, valsartan, telmisartan, irbesartan, tasosartan, etc.), calcium antagonists (e.g., nicardipine hydrochloride, manidipine hydrochloride, nisoldipine, nitrendipine, nilvadipine, amlodipine, etc.), etc. 
     The anti-obesity agent includes central anti-obesity agents (e.g., phentermine, sibutramine, amfepramone, dexamphetamine, mazindol, SR-141716A, etc.), pancreatic lipase inhibitors (e.g., orlistat, etc.), peptidic anorexiants (e.g., leptin, CNTF (ciliary neurotrophic factor), etc.), cholecystokinin agonists (e.g., lintitript, FPL-15849, etc.), etc. The diuretic includes xanthin derivative (e.g., sodium salicylate and theobromine, calcium salicylate and theobromine, etc.), thiazide preparations (e.g., ethiazide, cyclopenthiazide, trichlormethiazide, hydrochlorothiazide, hydroflumethiazide, bentyl hydrochlorothiazide, penflutizide, polythiazide, methyclothiazide, etc.), anti-aldosterone preparations (e.g., spironolactone, triamterene, etc.), carbonic anhydrase inhibitors (e.g., acetazolamide, etc.), chlorobenzenesulfonamide preparations (e.g., chlortalidone, mefruside, indapamide, etc.), azosemide, isosorbide, ethacrynic acid, piretanide, bumetanide, flosemide, etc. 
     The combination drug preferably includes GLP-1, GLP-1 analogs, alpha-glucosidase inhibitors, biguanides, insulin secretagogues, insulin resistance improving agents, DPP-IV inhibitors. The two or more combination drugs may be combined in any proportions. 
     The inventive compound may be combined with a combination drug to reduce dosages thereof within safe limits in terms of side effects of drugs. For example, biguanides may be reduced in lower doses than usual ones. Thus, side effects caused by the drugs may be safely prevented. In addition, dosages of a therapeutic agent for diabetic complication, anti-hyperlipidemia, antihypertensive, etc. may be reduced, and hence, side effects caused by the drugs may be effectively prevented. 
     Specific examples of the inventive compound of the general formula (1) may include the following compounds. 
     
       
         
           
               
            
               
                   
               
               
                 [Chemical Formula 19] 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
               
            
           
           
               
               
               
               
               
            
               
                   
                 A 
                 R C   
                 R D   
                 —NR A R B   
               
               
                   
                   
               
               
                   
                 CONH 2   
                 Et 
                 H 
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 CONH 2   
                 Et 
                 Cl 
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 CONH 2   
                 Me 
                 Me 
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 CONH 2   
                 Me 
                 Cl 
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 CONH 2   
                 Me 
                 Cl 
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 CONH 2   
                 Me 
                 Cl 
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 CONH 2   
                 Me 
                 Cl 
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 OH 
                 Me 
                 Cl 
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 CONH 2   
                 Me 
                 Cl 
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
            
           
         
       
     
     
       
         
           
               
            
               
                   
               
               
                 [Chemical Formula 20] 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
               
            
           
           
               
               
               
               
               
            
               
                   
                 A 
                 R C   
                 R D   
                 —NR A R B   
               
               
                   
                   
               
               
                   
                 OH 
                 Me 
                 Cl 
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 CONH 2   
                 Me 
                 Cl 
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 OH 
                 Me 
                 Cl 
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 CONH 2   
                 Me 
                 Cl 
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 OH 
                 Me 
                 Cl 
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 OH 
                 Me 
                 Cl 
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 CONH 2   
                 Me 
                 Cl 
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 CONH 2   
                 Me 
                 Cl 
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 OH 
                 Me 
                 Cl 
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
            
           
         
       
     
     
       
         
           
               
            
               
                   
               
               
                 [Chemical Formula 21] 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
               
            
           
           
               
               
               
               
               
            
               
                   
                 A 
                 R C   
                 R D   
                 —NR A R B   
               
               
                   
                   
               
               
                   
                 OH 
                 Me 
                 Cl 
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 CONH 2   
                 Me 
                 H 
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 CONH 2   
                 Me 
                 Cl 
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 CONH 2   
                 Me 
                 H 
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 OH 
                 Me 
                 H 
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 CONH 2   
                 Me 
                 H 
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 OH 
                 Me 
                 Cl 
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
            
           
         
       
     
     A preparation method of the inventive compound of formula (1) is illustrated by an example as follows, but the invention is not limited thereto. 
     A compound of formula (1) may be synthesized by the following methods. 
     Preparation 1 
     Among a compound of formula (1), a compound of formula (A-8) or a salt thereof may be prepared by the following methods. 
     
       
         
         
             
             
         
       
     
     (In the above scheme, R A , R B , R C , R D , R E  and R F  are the same as defined above. R is methyl, ethyl or benzyl, etc. X is halogen atom, etc. Provided that R D  is not halogen atom.) 
     Step 1: 
     R A R B NH (A-1) gives thiosemicarbazide (A-2) in the step. 
     Amine (A-1) may be reacted with 1,1′-thiocarbonyldiimidazole or thiophosgene in an inert solvent usually at −10° C. to 50° C. for 0.5 to 48 hours, and then, further reacted with hydrazine or hydrazine monohydrate usually at −10° C. to reflux temperature for 0.5 to 8 hours to give thiosemicarbazide (A-2). The inert solvent includes ether type solvents such as tetrahydrofuran, diethylether, dioxane or 1,2-dimethoxyethane, hydrocarbon solvents such as toluene or benzene, polar organic solvents such as N,N-dimethylformamide, N,N-dimethylacetamide, N-methyl-2-pyrrolidinone, 1,3-dimethyl-2-imidazolidinone or dimethylsulfoxide, halogenated hydrocarbon solvents such as dichloromethane, chloroform or 1,2-dichloroethane, or a mixed solvent thereof. 
     Alternatively, amine (A-1) is reacted with aryl halothioformate in an inert solvent usually at −40° C. to 50° C. for 0.5 to 24 hours in the presence of a base. The obtained thiocarbamate may be reacted with hydrazine or hydrazine monohydrate in an inert solvent usually at −10° C. to reflux temperature for 0.5 to 24 hours to give thiosemicarbazide (A-2). The inert solvent includes ether type solvents such as tetrahydrofuran, diethylether, dioxane or 1,2-dimethoxyethane, hydrocarbon solvents such as toluene or benzene, halogenated hydrocarbon solvents such as dichloromethane, chloroform or 1,2-dichloroethane, polar organic solvents such as N,N-dimethylformamide, N,N-dimethylacetamide, N-methyl-2-pyrrolidinone, 1,3-dimethyl-2-imidazolidinone or dimethylsulfoxide, water, or a mixed solvent thereof. The base may be optionally selected from nitrogen-containing organic bases such as triethylamine, diisopropylethylamine, tributylamine, 1,5-diazabicyclo [4.3.0] non-5-ene (DBN), 1,4-diazabicyclo [2.2.2] octane (DABCO), 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), pyridine, dimethylaminopyridine, picoline or N-methylmorpholine (NMM), etc., or inorganic bases such as sodium bicarbonate, potassium bicarbonate, sodium carbonate, potassium carbonate, sodium hydroxide or potassium hydroxide, etc. 
     Step 2: 
     Thiosemicarbazide (A-2) may be reacted with alpha-halo ketoester (A-3) in an inert solvent usually at −10° C. to reflux temperature for 0.5 to 48 hours to give Compound (A-4). In the reaction, nitrogen-containing organic bases such as triethylamine, diisopropylethylamine, tributylamine, 1,5-diazabicyclo[4.3.0]non-5-ene (DBN), 1,4-diazabicyclo[2.2.2]octane (DABCO), 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), pyridine, dimethylaminopyridine, picoline or N-methylmorpholine (NMM), or inorganic bases such as sodium bicarbonate, potassium bicarbonate, sodium carbonate, potassium carbonate, sodium hydroxide or potassium hydroxide may be optionally added to the reaction mixture. The inert solvent includes ether type solvents such as tetrahydrofuran, diethylether, dioxane or 1,2-dimethoxyethane, hydrocarbon solvents such as toluene or benzene, polar organic solvents such as dimethylsulfoxide, alcoholic solvents such as methanol, ethanol or 2-propanol, halogenated hydrocarbon solvents such as dichloromethane, chloroform or 1,2-dichloroethane, water, or a mixed solvent thereof, etc. 
     Step 3: 
     Compound (A-4) may be treated with an organic acid such as propionic acid, acetic acid, formic acid, methanesulfonic acid, toluenesulfonic acid or trifluoroacetic acid, or a mineral acid such as hydrogen chloride, sulfuric acid or hydrogen bromide, etc. in an inert solvent or in neat usually at −10° C. to reflux temperature for 0.5 to 48 hours to give pyrazole (A-5). The inert solvent includes ether type solvents such as tetrahydrofuran, diethylether, dioxane or 1,2-dimethoxyethane, hydrocarbon solvents such as toluene or benzene, polar organic solvents such as dimethylsulfoxide, alcoholic solvents such as methanol, ethanol or 2-propanol, water, or a mixed solvent thereof, and any stable solvents under the reaction condition may be used among them. 
     Step 4: 
     Compound (A-2) gives pyrazole (A-5) in the step without isolating or purifying Compound (A-4). 
     The reaction system of Step 2 or a concentration residue thereof may be treated with the acid listed in Step 3 at −10° C. to reflux temperature for 0.5-48 hours to give pyrazole (A-5). The reaction may be also carried out with removing a solvent from the reaction system to give pyrazole (A-5) in the step. The solvent in an addition of acid may be selected from ether type solvents such as tetrahydrofuran, diethylether, dioxane or 1,2-dimethoxyethane, hydrocarbon solvents such as toluene or benzene, polar organic solvents such as dimethylsulfoxide, alcoholic solvents such as methanol, ethanol or 2-propanol, water, or a mixed solvent thereof, which may be stable under the reaction condition. 
     Step 5: 
     Compound (A-5) is treated with a base, followed by treating with an alkylating agent such as dialkyl sulfate or alkyl halide at −78° C. to reflux temperature to give a compound of formula (A-6) in the step. 
     The base includes inorganic bases such as potassium carbonate, sodium carbonate, potassium bicarbonate, sodium bicarbonate, lithium carbonate, sodium hydroxide or potassium hydroxide, metal hydrides such as sodium hydride, lithium hydride or potassium hydride, metal alkoxides such as sodium methoxide, potassium methoxide, sodium ethoxide, potassium ethoxide, sodium tertiary-butoxide or potassium tertiary-butoxide, potassium hexamethyldisilazide, sodium hexamethyldisilazide, lithium hexamethyldisilazide, or lithium diisopropylamide. The solvent includes ether type solvents such as diethylether, diisopropylether, tetrahydrofuran or 1,4-dioxane, N,N-dimethylformamide, N,N-dimethylacetamide, N-methyl-2-pyrrolidinone, 1,3-dimethyl-2-imidazolidinone, or dimethylsulfoxide. 
     Step 6: 
     An ester group of Compound (A-6) is deprotected to give a carboxylic acid compound (A-7) in the step. The step may be carried out according to methods described in Greene&#39;s Protective Groups in Organic Synthesis, John Wiley &amp; Sons Inc., 1981. 
     Specifically, the following methods are carried out in the step. 
     (A) Compound (A-6) wherein R is methyl, ethyl, etc. may be converted to a corresponding carboxylic acid by alkali hydrolysis or acid hydrolysis. Specifically, Compound (A-6) may be treated in the presence of a hydroxide of alkali metal or alkaline-earth metal such as sodium hydroxide, potassium hydroxide, lithium hydroxide or magnesium hydroxide in water, or water and alcoholic solvents such as methanol, ethanol, 2-propanol or butanol, ether type solvents such as diethylether, diisopropylether, tetrahydrofuran or 1,4-dioxane, aromatic hydrocarbon solvents such as benzene, toluene or xylene, or a mixed solvent thereof usually at room temperature to reflux temperature for 0.5 to 48 hours to give Compound (A-7).
 
(B) Compound (A-6) wherein R is benzyl may be reacted in the presence of a metal catalyst such as palladium/carbon, palladium hydroxide, platinum, platinum oxide or nickel, etc. with the addition of hydrogen chloride, ammonium formate, if needed, under hydrogen gas to give Compound (A-7). The solvent includes alcoholic solvents such as methanol, ethanol, 2-propanol or butanol, ether type solvents such as diethylether, diisopropylether, tetrahydrofuran or 1,4-dioxane, aromatic hydrocarbon solvents such as benzene, toluene or xylene, ester type solvents such as ethyl acetate or methyl acetate, organic acids such as acetic acid, or a mixed solvent thereof
 
     Step 7: 
     Carboxyl group of Compound (A-7) is activated, followed by reacting with amine R E R F NH or a salt thereof to give Compound (A-8) in the step. 
     The activation method of carboxy group includes a method wherein carboxy group is converted to acid anhydride, mixed acid anhydride, acid halide, activated ester or acid azide, or a method wherein a condensing agent is used. 
     Using the acid halide method, Compound (A-7) may be reacted with a halogenating agent such as oxalyl chloride, thionyl chloride, phosphorus oxychloride or phosphorus pentachloride to give an acid halide, followed by reacting with amine R E R F NH or a salt thereof in the presence of a base to give Compound (A-8). The base includes organic bases such as triethylamine, diisopropylethylamine, tributylamine, 1,5-diazabicyclo[4.3.0]non-5-ene (DBN), 1,4-diazabicyclo[2.2.2]octane (DABCO), 1,8-diazabicyclo [5.4.0] undec-7-ene (DBU), pyridine, dimethylaminopyridine, picoline or N-methylmorpholine (NMM), or inorganic bases such as sodium bicarbonate, potassium bicarbonate, sodium carbonate, potassium carbonate, sodium hydroxide or potassium hydroxide, without any limitation. Any solvents which may be stable under the reaction condition may be used in the step. For example, such solvents include halogenated hydrocarbon solvents such as dichloromethane, chloroform, 1,2-dichloroethane or carbon tetrachloride, ether type solvents such as diethylether, diisopropylether, tetrahydrofuran or 1,4-dioxane, aromatic hydrocarbon solvents such as benzene, toluene or xylene, ester type solvents such as ethyl acetate or methyl acetate, water, or a mixture thereof. The reaction temperature is in the range of −80° C. to reflux temperature, usually at −20° C. to ice-cooling temperature. 
     The reaction time is in the range of 10 minutes to 48 hours. 
     Using the mixed acid anhydride method, Compound (A-7) may be reacted with an acid halide in the presence of a base to give a mixed acid anhydride, followed by reacting with amine R E R F NH or a salt thereof to give Compound (A-8). The acid halide includes methoxycarbonyl chloride, ethoxycarbonyl chloride, isopropyloxycarbonyl chloride, isobutyloxycarbonyl chloride, para-nitrophenoxy carbonyl chloride or t-butylcarbonyl chloride. The base includes organic bases such as triethylamine, diisopropylethylamine, tributylamine, 1,5-diazabicyclo[4.3.0]non-5-ene (DBN), 1,4-diazabicyclo[2.2.2]octane (DABCO), 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), pyridine, dimethylaminopyridine, picoline or N-methylmorpholine (NMM), or inorganic bases such as sodium bicarbonate, potassium bicarbonate, sodium carbonate or potassium carbonate, without any limitation. Any solvents which may be stable under the reaction condition may be used in the step. For example, such solvents include halogenated hydrocarbon solvents such as dichloromethane, chloroform, 1,2-dichloroethane or carbon tetrachloride, ether type solvents such as diethylether, diisopropylether, tetrahydrofuran or 1,4-dioxane, aromatic hydrocarbon solvents such as benzene, toluene or xylene, ester type solvents such as ethyl acetate or methyl acetate, water, or a mixture thereof. The reaction temperature is in the range of −80° C. to reflux temperature, usually at −20° C. to ice-cooling temperature. The reaction time is in the range of 30 minutes to 48 hours. 
     Compound (A-7) may be reacted with amine R E R F NH or a salt thereof using a condensing agent in the presence or absence of a base to give Compound (A-8). The condensing agent includes substances listed in The Experimental Chemistry (Jikken Kagaku Koza), edited by The Chemical Society of Japan, Maruzen, Vol. 22, e.g., phosphoric acid esters such as diethyl cyanophosphate or diphenyl phosphoryl azide, carbodiimides such as 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide hydrochloride or dicyclohexylcarbodiimide, combinations of disulfides such as 2,2′-dipyridyl disulfide with phosphines such as triphenylphosphine, phosphorus halides such as N,N′-bis(2-oxo-3-oxazolidinyl)phosphinic chloride, combinations of azodicarboxylic acid diesters such as diethyl azodicarboxylate with phosphines such as triphenylphosphine, 2-halo-1-lower alkylpyridinium halides such as 2-chloro-1-methylpyridinium iodide, 1,1′-carbonyldiimidazole, diphenyl phosphoryl azide (DPPA), diethylphosphoryl cyanide (DEPC), dicyclohexylcarbodiimide (DCC), carbonyldiimidazole (CDI), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC.HCl), O-(1H-benzotriazol-1-yl)-1,1,3,3-tetramethyl-uronium tetrahydroborate (TBTU), O-(1H-benzotriazol-1-yl)-N,N,N′,N′-tetramethyl-uronium hexafluorophosphate (HBTU), or (benzotriazol-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate. Any solvents which may be stable under the reaction condition may be used in the step without any limitation. Specifically, the same solvents used in the acid-halide method, or aprotic polar solvents such as N,N-dimethylformamide, N,N-dimethylacetamide, N-methyl-2-pyrrolidinone, 1,3-dimethyl-2-imidazolidinone or dimethylsulfoxide, water, or a mixed solvent thereof may be used. The base includes organic bases such as triethylamine, diisopropylethylamine, tributylamine, 1,5-diazabicyclo[4.3.0]non-5-ene (DBN), 1,4-diazabicyclo[2.2.2] octane (DABCO), 1,8-diazabicyclo[5.4.0] undec-7-ene (DBU), pyridine, dimethylaminopyridine, picoline or N-methylmorpholine (NMM) without any limitation. The reaction is usually carried out at −10° C. to reflux temperature. The reaction time is usually 0.5 to 48 hours depending mainly on reaction temperatures, starting materials and solvents. 
     The invention encompasses the following embodiments [PC1]-[PC13]. 
     [PC1] A process for preparing pyrazole (A-5), wherein a reaction system with a base is applied before the addition of an acid in the step in which thiosemicarbazide (A-2) is treated with alpha-halo ketoester (A-3) to give pyrazole (A-5) with or without isolating Compound (A-4).
 
[PC2] The process for preparing of [PC1], wherein the base added in the reaction is an inorganic base.
 
[PC3] The process for preparing of [PC1], wherein the inorganic base added in the reaction is one or more combinations selected from sodium bicarbonate, potassium bicarbonate, lithium bicarbonate, sodium carbonate, potassium carbonate or lithium carbonate.
 
[PC4] A process for preparing pyrazole (A-5), wherein the reaction system contains water before the addition of an acid in the step in which thiosemicarbazide (A-2) is treated with alpha-halo ketoester (A-3) to give pyrazole (A-5) with or without isolating Compound (A-4).
 
[PC5] A process for preparing pyrazole (A-5), wherein the reaction system is concentrated before the addition of an acid in the step in which thiosemicarbazide (A-2) is treated with alpha-halo ketoester (A-3) to give pyrazole (A-5) with or without isolating Compound (A-4).
 
[PC6] A process for preparing pyrazole (A-5), wherein the reaction is carried out with removing solvents from the reaction system after the addition of an acid in the steps in which thiosemicarbazide (A-2) is treated with alpha-halo ketoester (A-3) to give pyrazole (A-5).
 
[PC7] A process for preparing pyrazole (A-5), wherein the reaction is carried out with evaporating solvents from the reaction system after the addition of an acid in the steps in which thiosemicarbazide (A-2) is treated with alpha-halo ketoester (A-3) to give pyrazole (A-5).
 
[PC8] A process for preparing pyrazole (A-5), wherein the added acid is an organic acid or inorganic acid in the step in which thiosemicarbazide (A-2) is treated with alpha-halo ketoester (A-3) to give pyrazole (A-5) with or without isolating Compound (A-4).
 
[PC9] The process for preparing of [PC8], wherein the added acid is one or more combinations selected from hydrochloric acid, hydrobromic acid, sulfuric acid, propionic acid, acetic acid, formic acid, methanesulfonic acid, toluenesulfonic acid or trifluoroacetic acid.
 
[PC10] The process for preparing of [A8], wherein the added acid is acetic acid.
 
[PC11] A process for preparing pyrazole (A-5), comprising one to four combinations selected from [PC1] to [PC3], [PC4], [PC5] to [PC7], [PC8] to [PC10] in the step in which thiosemicarbazide (A-2) is treated with alpha-halo ketoester (A-3) to give pyrazole (A-5) with or without isolating Compound (A-4).
 
[PC12] A process for preparing pyrazole (A-5), comprising a combination selected from [PC3], [PC4], [PC5] or [PC7], and [PC10] in the steps in which thiosemicarbazide (A-2) is treated with alpha-halo ketoester (A-3) to give pyrazole (A-5) with or without isolating Compound (A-4).
 
[PC13] A process for preparing pyrazole (A-5) of [PC11] or [PC12], wherein R A  and/or R B  of thiosemicarbazide (A-2) contain the same or different one or more groups selected from Cbz, Boc, tetrahydrofuranyl, tetrahydropyranyl, cyclopropyl, cyclobutyl, optionally substituted benzyloxy or optionally substituted benzylamino as a partial structure.
 
     Preparation 2 
     A compound of formula (A-12) or a salt thereof among a compound of formula (1) is, for example, prepared according to the following methods. 
     
       
         
         
             
             
         
       
     
     (In the above scheme, R A , R B , R C , R E  and R F  are the same as defined above. R is methyl, ethyl, benzyl, etc. X is halogen atom, etc.) 
     Step 8: 
     Halogen (X) is introduced at 4-position of pyrazole ring in Compound (A-9) to give Compound (A-10) in the step. 
     Halogen atom may be introduced at 4-position in Compound (A-9) by adding a halogenating agent such as N-chlorosuccinimide, N-bromosuccinimide, chlorine, bromine, iodine, iodine chloride, sulfuryl chloride, SELECTFLUOR®, 1-fluoro-4-hydroxy-1,4-diazoniabicyclo[2.2.2] octane bis(tetrafluoroborate), N-fluorobenzenesulfonimide, N-fluoro-o-benzenedisulfonimide, 1-fluoropyridinium triflate or 1-fluoro-2,6-dichloropyridinium tetrafluoroborate in the presence or absence of an acid. The acid includes hydrogen halides such as hydrogen chloride or hydrogen bromide, or organic acids such as acetic acid or propionic acid. The reaction may be also carried out using a base instead of an acid. The base includes inorganic bases such as sodium bicarbonate, potassium bicarbonate, sodium carbonate or potassium carbonate. Any solvents which may be inert under the reaction condition may be used in the step, e.g., ester type solvents such as ethyl acetate or methyl acetate, halogenated hydrocarbon solvents such as dichloromethane, chloroform, 1,2-dichloroethane or carbon tetrachloride, aprotic polar solvents such as N,N-dimethylformamide, N,N-dimethylacetamide, N-methyl-2-pyrrolidinone or 1,3-dimethyl-2-imidazolidinone, water, or a mixed solvent thereof. The reaction temperature is usually in the range of −10° C. to reflux temperature. The reaction time is usually in the range of 0.5 to 48 hours. 
     Compound (A-10) may be treated by Steps 9-10 of the similar method to Preparation 1 to give Compound (A-12). 
     Compound (A-9) may be treated by Steps 11-12 of the similar method to Preparation 1 to give Compound (A-14). 
     Compound (A-14) may be treated by the similar method to Step 8 to give Compound (A-12). 
     Preparation 3 
     A compound of formula (A-17) or a salt thereof among a compound of formula (1) is prepared according to the following method. 
     
       
         
         
             
             
         
       
     
     (In the above scheme, R B , R C , R D , R E , R F  and p are the same as defined above. Pro is a protective group of nitrogen atom. B 3  is acyl or sulfonyl.) 
     Step 14: 
     Compound (A-15) wherein Pro is benzyloxycarbonyl may be treated in the following manner to give Compound (A-16). Compound (A-15) may be treated with hydrogen in an inert solvent usually at ambient temperature to 50° C. for 0.5 to 24 hours in the presence of palladium/carbon to give Compound (A-16). Hydrogen may be used at normal pressure or with pressurized. The inert solvent includes halogenated hydrocarbon solvents such as dichloromethane, chloroform, 1,2-dichloroethane or carbon tetrachloride, ether type solvents such as diethylether, diisopropylether, tetrahydrofuran or 1,4-dioxane, aromatic hydrocarbon solvents such as benzene, toluene or xylene, ester type solvents such as ethyl acetate or methyl acetate, water, or a mixed solvent thereof. Ammonium formate may be used instead of hydrogen. 
     Step 15: 
     Acylation or sulfonylation of a deprotected amine of Compound (A-16) may give Compound (A-17) in the step. 
     The acylation may be carried out in the similar manner to Step 7 of Preparation 1 by using acid halide or carboxylic acid compound to give Compound (A-17) as an amide derivative. 
     The sulfonylation may be carried out in the similar manner to the acid-halide method of Step 7 of Preparation 1 by using sulfonyl halide such as arylsulfonyl halide to give Compound (A-17) as a sulfoneamide derivative. 
     Preparation 4 
     A compound of formula (A-18) or a salt thereof among a compound of formula (1) is prepared by the following method. 
     
       
         
         
             
             
         
       
     
     (In the above scheme, R B , R C , R D , R E , R F  and p are the same as defined above. R G  and R H  are each hydrogen atom, optionally substituted alkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted cycloalkyl or optionally substituted heterocycloalkyl. Alternatively, R G  and R H  may combine each other together with the adjacent nitrogen atom to form an optionally substituted saturated heterocycle.) 
     Compound (A-16) is treated with amine R G R H NH or a salt thereof to give Compound (A-18) in the step. Amine R G R H NH is reacted with 1,1′-carbonyldiimidazole, triphosgene, diphosgene or phosgene in an inert solvent usually at −10° C. to 30° C. for 0.5 to 6 hours, followed by reacting with Compound (A-16) at −10° C. to reflux temperature for 0.5 to 8 hours. Compound (A-16) may be also treated earlier than amine R G R H NH. Consequently, Compound (A-18) may be prepared in this manner. Amine R G R H NH may be also reacted with para-nitrophenyl chloroformate or trichloromethyl chloroformate in the presence of a base in an inert solvent usually at −10° C. to 30° C., followed by reacting with Compound (A-16) usually at −10° C. to reflux temperature to give Compound (A-18). Compound (A-16) may be also treated earlier than amine R G R H NH. The base includes nitrogen-containing organic bases such as triethylamine, diisopropylethylamine, tributylamine, 1,5-diazabicyclo[4.3.0]non-5-ene (DBN), 1,4-diazabicyclo[2.2.2]octane (DABCO), 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), pyridine, dimethylaminopyridine, picoline or N-methylmorpholine (NMM), or inorganic bases such as potassium carbonate, sodium carbonate or sodium bicarbonate. 
     The inert solvent includes ether type solvents such as tetrahydrofuran, diethylether, dioxane or 1,2-dimethoxyethane, hydrocarbons such as toluene or benzene, halogenated hydrocarbon solvents such as dichloromethane, chloroform or 1,2-dichloroethane, aprotic polar solvents such as dimethylsulfoxide, N,N-dimethylformamide, N,N-dimethylacetamide, N-methyl-2-pyrrolidinone or 1,3-dimethyl-2-imidazolidinone, a mixed solvent thereof, or a mixed solvent of these solvents with water. 
     Compound (A-16) may be also treated with isocyanate R G NCO, wherein R G  is not hydrogen atom, to give Compound (A-18). 
     Compound (A-16) may be treated with isocyanate R G NCO usually at −10° C. to reflux temperature in an inert solvent or neat in the presence or absence of a base to give Compound (A-18). The base includes nitrogen-containing organic bases such as triethylamine, diisopropylethylamine, tributylamine, 1,5-diazabicyclo[4.3.0]non-5-ene (DBN), 1,4-diazabicyclo[2.2.2]octane (DABCO), 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), pyridine, dimethylaminopyridine, picoline or N-methylmorpholine (NMM), or inorganic bases such as potassium carbonate, sodium carbonate or sodium bicarbonate. The inert solvent includes ether type solvents such as tetrahydrofuran, diethylether, dioxane or 1,2-dimethoxyethane, hydrocarbons such as toluene or benzene, halogenated hydrocarbon solvents such as dichloromethane, chloroform or 1,2-dichloroethane, aprotic polar solvents such as dimethylsulfoxide, N,N-dimethylformamide, N,N-dimethylacetamide, N-methyl-2-pyrrolidinone or 1,3-dimethyl-2-imidazolidinone, a mixed solvent thereof, or a mixed solvent of these solvents with water. 
     Preparation 5 
     
       
         
         
             
             
         
       
     
     (In the above scheme, R B , R C , R D , R E , R F  and p are the same as defined above. B 4  is aryl or heteroaryl.) 
     Compound (A-16) may be treated with halogenated aryl or halogenated heteroaryl (B 4 —Br, B 4 —I, B 4 —Cl, etc.) or aryl metal compound or heteroaryl metal compound (B 4 -Mtl) to give Compound (A-19), in which -Mtl is a boronic acid group —B(OH) 2 , —B(OMe) 2  as a boronic acid ester group, —ZnCl as a zinc halide group, etc. 
     Compound (A-16) may be treated with halogenated aryl, halogenated heteroaryl, aryl metal compound or heteroaryl metal compound usually at room temperature to reflux temperature in the presence or absence of a palladium, copper or nickel metal catalyst such as tetrakis(triphenylphosphine)palladium, dichlorodi(tris-o-tolylphosphine)palladium, tris(dibenzylidene-acetone)dipalladium, copper acetate, copper iodide, nickel di(cyclooctadienyl) or nickel-carbon in the presence of a base such as sodium tertiary-butoxide, potassium carbonate, sodium bicarbonate or lithium hexamethyldisilazide, or a phosphorus ligand such as 2,2′-bis(diphenylphosphino)-1,1′-binaphthyl or triphenylphosphine, if needed, in an inert solvent or neat to give Compound (A-19). The solvent includes ether type solvents such as diethylether, diisopropylether, 1,2-dimethoxyethane, tetrahydrofuran or 1,4-dioxane, aromatic hydrocarbon solvents such as benzene, toluene or xylene, aprotic polar solvents such as dimethylsulfoxide, N,N-dimethylformamide, N,N-dimethylacetamide, N-methyl-2-pyrrolidinone or 1,3-dimethyl-2-imidazolidinone, water, or a mixture thereof. The reaction time is usually in the range of 30 minutes to 48 hours. 
     If any functional groups except for the intended reaction sites may be affected under the reaction conditions or be inappropriate to carry out the reactions in the above Preparations, such groups except for the intended reaction sites may be protected to carry out the reactions, followed by deprotecting to give the desired compounds. The protective group includes conventional protective groups described in the Protective Groups in Organic Synthesis as mentioned above, and specifically, the protective group for amine includes ethoxycarbonyl, t-butoxycarbonyl, acetyl or benzyl, and that of hydroxyl includes tri-lower alkyl silyl, acetyl or benzyl. 
     An introduction or deprotection of a protective group may be carried out according to a conventional method in the organic synthetic chemistry (see, for example, the Protective Groups in Organic Synthesis), or with some modification thereof. 
     Any functional groups of any intermediates or final products may be also optionally modified to give other compounds encompassed in the invention in the above Preparations. The modification of functional groups may be carried out by a conventional method (see, for example, R. C. Larock, Comprehensive Organic Transformations, 1989). 
     Each intermediate and the desired compound may be isolated and/or purified by a conventional purification method in the organic synthetic chemistry, e.g. neutralization, filtration, extraction, washing, drying, concentration, recrystallization, various chromatography, etc., in each Preparation. Each intermediate may be also used in the next reaction without purification. 
     Any optical isomers may be isolated in any steps in the above Preparations by a conventional isolating method including a method using an optically-active column or a fractionated crystallization. Any optically-active starting materials may be also used in the Preparations. 
     The invention encompasses any possible isomers including optical isomers, stereoisomers, tautomers such as ketoenol, and/or geometrical isomers, and a mixture thereof. 
     Any starting materials and intermediates may be known compounds, or be synthesized therefrom by a conventional method in the Preparations. 
     A configuration of two substituents on adamantane group in the inventive compound is defined as Z or E relative configuration according to C. D. Jones, M. Kaselj, et al. J. Org. Chem. 63: 2758-2760, 1998. 
     The invention is illustrated by the following Reference Examples, Examples and Test Examples in more detail, but is not limited thereto. Compound names do not necessarily follow IUPAC nomenclature in the following Reference Examples and Examples. 
     The following abbreviations may be used in the Reference Examples and Examples. 
     THF: tetrahydrofuran
 
NaBH(OAc) 3 : sodium triacetoxyborohydride
 
(Boc) 2 O: di-tert-butyldicarbonate
 
Pd(OH) 2 : palladium hydroxide
 
     DMF: N,N-dimethylformamide 
     WSC.HCl: 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride
 
HOBt.H 2 O: 1-hydroxybenzotriazole monohydrate
 
NMP: 1-methyl-2-pyrrolidinone
 
Me: methyl
 
Et: ethyl
 
Boc: tert-butoxycarbonyl
 
Cbz: benzyloxycarbonyl
 
N: normal (e.g., 2N HCl is 2-normal hydrochloric acid.)
 
M: molar concentration (mol/L) (e.g., 2M methylamine is 2 mol/L methylamine solution.)
 
t R : retention time
 
     A reverse-phase preparative purification was carried out as below. 
     A purification was carried out by using Gilson HPLC System. YMC CombiPrep ODS-A column (5 μm, 50×20 min I.D.) was used, and a mixed solvent system of CH 3 CN (containing 0.035% TFA) with water (containing 0.05% TFA) was used. UV was detected in each wavelength of 210 nm, 220 nm and 254 nm 
     Elution conditions were as follows. 
     Preparative instrument: Gilson HPLC System 
     Column: YMC CombiPrep ODS-A 50×20 min I.D. 
     Solvent: CH 3 CN (containing 0.035% TFA), water (containing 0.05% TFA)
 
Flow rate: 35 mL/min
 
Gradient: linear gradient from 1:99 (v/v) CH 3 CN/water to 95:5 (v/v) CH 3 CN/water within 13 min at 35 mL/min
 
obsMS [M+1]: observed protonated molecules
 
min: minute
 
     LC/MS analytic conditions for identifying compounds in reverse-phase preparative purifications were as follows. 
     Measurement method SA:
 
Detection device: Detector Perkin-Elmer Sciex API150EX Mass spectrometer (40 eV)
 
     HPLC: Shimadzu LC 10ATVP 
     Column: Shiseido CAPCELL PAK C18 ACR(S-5 um, 4.6×50 mm) 
     Solvent: Solution A: 0.35% TFA/CH 3 CN, Solution B: 0.05% TFA/H 2 O 
     Gradient condition: 0.0-0.5 min A 10%, 0.5-4.8 min Linear gradient from A 10% to 99%, 4.8-5.0 min A 99%
 
Flow rate: 3.5 mL/min
 
     UV: 254 nm 
     Measurement method SB:
 
Detection device: Agilent 1100 series for API series, manufactured by Applied Biosystems
 
HPLC: API150EX LC/MS system, manufactured by Applied Biosystems
 
     Column: YMC CombiScreen ODS-A (S-5 μm, 12 nm, 4.6×50 mm) 
     Solvent: Solution A: 0.05% TFA/H 2 O, Solution B: 0.035% TFA/MeCN 
     Gradient condition: 0.0-0.5 min A 90%, 0.5-4.2 min Linear gradient from A 90% to 1%, 4.2-4.4 min
 
Linear gradient from A 1% to 99%
 
Flow rate: 3.5 mL/min
 
     UV: 220 nm 
     EXAMPLES 
     Reference Example 1 
     Methyl 4-aminoadamantane-1-carboxylate hydrochloride 
     
       
         
         
             
             
         
       
     
     Step (i): 
     To a solution of Compound I (40.0 g) (see The Journal of Organic Chemistry, 1983, Vol. 48, page 1099) in methanol (500 mL) was added thionyl chloride (22.7 mL). The mixture was heated to reflux and stirred for 3 hours. Then, the mixture was concentrated in vacuo, and then extracted with saturated sodium bicarbonate water and ethyl acetate. The organic layer was dried over sodium sulfate and concentrated in vacuo to give Compound II (44.0 g). 
     Step (ii): 
     Compound II (55.4 g) was dissolved in dichloromethane (1.25 L), and thereto were added (R)-(+)-1-phenetylamine (32.2 g), NaBH(OAc) 3  (82.0 g) and acetic acid (10 mL). The mixture was stirred at room temperature overnight. The mixture was treated with 6N hydrochloric acid, and then basified by 2N sodium hydroxide solution and extracted with chloroform. The organic layer was dried over sodium sulfate and concentrated in vacuo. The residue was purified by silica gel column chromatography (eluent: chloroform/meththanol=100/0 to 98/2) to give Compound III (73.6 g). 
     Step (iii): 
     To a solution of Compound III (12.6 g) in acetic acid (200 mL) was added palladium hydroxide (6.0 g), and the mixture was stirred under hydrogen (3 atm) for 9 hours. The palladium was filtered off, and then the filtrate was concentrated in vacuo. The residue was dissolved in saturated sodium bicarbonate water and THF, and thereto was added (Boc) 2 O (9.65 g). The mixture was stirred at room temperature for 1.5 hours. The reaction solution was extracted with ethyl acetate and saturated sodium bicarbonate water. The organic layer was dried over sodium sulfate and concentrated in vacuo. The residue was purified by silica gel column chromatography (eluent: chloroform/meththanol=19/1), and dissolved in chloroform (150 mL). Then, thereto was added 4N hydrochloric acid-dioxane (50 mL), and the mixture was stirred at room temperature overnight. The mixture was concentrated in vacuo, and the resulting white solid was filtered and concentrated in vacuo to give the titled Compound IV (7.0 g). 
       1 H-NMR (DMSO-d 6 ) δ 1.50 (m, 1H), 1.70-1.80 (m, 4H), 1.87-2.06 (m, 6H), 2.06-2.10 (m, 3H), 3.31 (s, 3H), 8.17 (bs, 3H) 
     Reference Example 2 
     5-(Dimethylamino)-1-methyl-1H-pyrazole-3-carboxylic acid 
     
       
         
         
             
             
         
       
     
     Step (i): 
     To a solution of Compound I (20.0 g) in THF (400 mL) was added dropwise 2N dimethylamine-THF solution (56 mL), and the mixture was stirred at room temperature for 2 hours. Then, thereto was added dropwise hydrazine monohydrate (24 mL), and the mixture was stirred under reflux for 3 hours. The mixture was concentrated in vacuo, and then thereto was added saturated sodium bicarbonate water. The mixture was extracted with ethyl acetate, and the organic layer was dried over sodium sulfate and concentrated in vacuo to give Compound II (21.0 g). 
     Step (ii): 
     Compound II was dissolved in a mixed solvent of ethanol (100 mL) and THF (200 mL), and thereto were added sodium bicarbonate (16.2 g) and ethyl bromopyruvate (38.4 g). The mixture was stirred at 60° C. for 3 hours. Then, thereto was added 4N hydrochloric acid-dioxane (50 mL), and the mixture was stirred at 70° C. for 3 hours. The mixture was concentrated in vacuo, and then thereto was added saturated sodium bicarbonate water. The mixture was extracted with ethyl acetate. The organic layer was dried over sodium sulfate and concentrated in vacuo to give Compound III (21.0 g). 
     Step (iii): 
     Compound III (21.0 g) was dissolved in THF (1 L), and thereto was added sodium hydride (5.8 g) at 0° C. The mixture was stirred at 0° C. to room temperature for 1 hour. Then, thereto was added methyl iodide (8.2 mL) at 0° C., and the mixture was stirred at room temperature overnight. Thereto was added water, and then the mixture was concentrated in vacuo. Thereto was added saturated sodium bicarbonate water, and the mixture was extracted with ethyl acetate. The organic layer was dried over sodium sulfate and concentrated in vacuo. The residue was purified by silica gel chromatography (eluent: hexane/ethyl acetate=1/1) to give Compound IV (6.5 g). 
     Step (iv): 
     Compound IV (6.5 g) was dissolved in methanol (300 mL), and thereto was added 2N sodium hydroxide solution (30 mL) and the mixture was stirred at room temperature overnight. The reaction solution was concentrated in vacuo, and then acidified by 1N hydrochloric acid and extracted with ethyl acetate. The organic layer was dried over sodium sulfate and concentrated in vacuo to give Compound V (4.4 g) as a yellow oil. 
       1 H-NMR (DMSO-d 6 ) δ 2.62 (s, 6H), 3.69 (s, 3H), 6.21 (s, 1H), 12.4 (bs, 1H) 
     Reference Example 3 
     (E)-4-Aminoadamantan-1-ol hydrochloride 
     
       
         
         
             
             
         
       
     
     Step (i): 
     To a solution of 5-hydroxy-2-adamantanone (10.0 g) in dichloromethane (200 mL) were added (S)-(−)-1-phenetylamine (7.2 g), NaBH(OAc) 3  (19 g) and acetic acid (2 mL), and the mixture was stirred at room temperature for 4 hours. Thereto was added 1N hydrochloric acid, and the mixture was washed with chloroform, and then the aqueous layer was basified by 2N sodium hydroxide solution. The mixture was extracted with chloroform, dried over sodium sulfate, and concentrated in vacuo. The residue was purified by silica gel chromatography (eluent: chloroform/meththanol=10/1) to give Compound II (5.9 g) as a low-polar ingredient and Compound III (4.2 g) as a high-polar one. 
     Step (ii): 
     Compound II (5.9 g) was dissolved in acetic acid (80 mL), and thereto was added palladium hydroxide (3.0 g) and the mixture was stirred under hydrogen (3 atm) for 8.5 hours. The resulting solid was filtered through Celite®, and then the filtrate was concentrated. The residue was dissolved in THF (100 mL) and saturated sodium bicarbonate water (50 mL), and thereto was added (Boc) 2 O (4.7 g) and the mixture was stirred at room temperature for 4 hours. The reaction solution was extracted with ethyl acetate. The organic layer was dried over sodium sulfate and concentrated in vacuo. The residue was purified by silica gel chromatography (eluent: hexane/ethyl acetate=1/1) and dissolved in chloroform (100 mL), and thereto was added 4N hydrochloric acid-dioxane (20 mL) and the mixture was stirred at room temperature for 3 hours. The mixture was concentrated in vacuo and azeotroped with toluene to give Compound IV (4.9 g) as a white solid. 
       1 H-NMR (DMSO-d 6 ) δ 1.35-1.39 (m, 2H), 1.59-1.69 (m, 7H), 1.86-1.90 (m, 2H), 2.01 (m, 1H), 2.06-2.12 (m, 2H), 4.50 (bs, 1H), 8.07 (bs, 3H) 
     Reference Example 4 
     N-(3-Methoxybenzyl)cyclopropaneamine 
     
       
         
         
             
             
         
       
     
     Cyclopropaneamine (1.5 g) was dissolved in dichloromethane (50 mL), and thereto were added 3-methoxybenzaldehyde (3.5 g), NaBH(OAc) 3  (6.7 g) and acetic acid (1 mL) and the mixture was stirred at room temperature overnight. Thereto was added water, and then the mixture was extracted with chloroform. The organic layer was dried over sodium sulfate and concentrated in vacuo. The residue was purified by silica gel chromatography (eluent: chloroform/methanol=10/1) to give Compound II (2.8 g) as a colorless oil. 
       1 H-NMR (CDCl 3 ) δ 0.36-0.41 (m, 2H), 0.43-0.47 (m, 2H), 2.17 (m, 1H), 3.82 (s, 3H), 3.83 (s, 2H), 6.80 (m, 1H), 6.87-6.92 (m, 2H), 7.24 (m, 1H) 
     Reference Example 5 
     Ethyl-5-[cyclopropyl(3-methoxybenzyl)amino]-1-methyl-1H-pyrazole-3-carboxylate 
     
       
         
         
             
             
         
       
     
     Step (i): 
     To a solution of Compound I (2.8 g) in THF (150 mL) was added dropwise N-(3-methoxybenzyl)cyclopropaneamine (2.8 g), and the mixture was stirred at room temperature for 5 hours. Then, thereto was added dropwise hydrazine monohydrate (8 mL), and the mixture was stirred under reflux for 6 hours. The mixture was concentrated in vacuo, and then thereto was added saturated sodium bicarbonate water and the mixture was extracted with ethyl acetate. The organic layer was dried over sodium sulfate and concentrated in vacuo. The resulting white solid was filtered, washed with water and dried in vacuo to give Compound II (3.5 g). 
     Step (ii): 
     Compound II (1.3 g) was dissolved in ethanol (10 mL) and THF (10 mL), and thereto were added sodium bicarbonate (0.54 g) and ethyl bromopyruvate (1.5 g) and the mixture was stirred at 70° C. for 3 hours. Then, thereto was added acetic acid (1.2 mL) and the mixture was stirred at 60° C. for 4.5 hours. The mixture was concentrated in vacuo, and thereto was added saturated sodium bicarbonate water and the mixture was extracted with ethyl acetate. The organic layer was dried over sodium sulfate and concentrated in vacuo to give Compound III (62 mg). 
     Step (iii): 
     Compound III (62 mg) was dissolved in THF (5 mL), and thereto was added sodium hydride (9.4 mg) at 0° C. The mixture was stirred at 0° C. to room temperature for 1 hour. Then, thereto was added methyl iodide (13 μL) at 0° C. and the mixture was stirred at room temperature for 3 hours. Thereto was added water, then saturated sodium bicarbonate water, and the mixture was extracted with ethyl acetate. The organic layer was dried over sodium sulfate and concentrated in vacuo. The residue was purified by preparative TLC (eluent: hexane/ethyl acetate=1/1) to give Compound IV (24 mg). 
       1 H-NMR (CDCl 3 ) δ 0.71-0.74 (m, 2H), 0.76-0.80 (m, 2H), 1.38 (t, J=7.12 Hz, 3H), 2.54 (m, 1H), 3.58 (s, 3H), 3.78 (s, 3H), 4.36 (q, J=7.12 Hz, 2H), 4.53 (s, 2H), 6.43 (s, 1H), 6.76-6.85 (m, 3H), 7.20 (m, 1H) 
     Reference Example 6 
     N-[2-(4-Fluorophenoxy)ethyl]-N-methylhydrazinecarbothioamide 
     
       
         
         
             
             
         
       
     
     Step (i): 
     Compound I (41.3 g) was dissolved in THF (100 mL), and thereto were added saturated sodium bicarbonate water (100 mL) and (Boc) 2 O (120 g) and the mixture was stirred at room temperature overnight. Thereto was added water, and the mixture was extracted with ethyl acetate. The organic layer was dried over sodium sulfate and then concentrated in vacuo to give Compound II (94.4 g). 
     Step (ii): 
     Compound II (5.0 g) was dissolved in THF (200 mL), and thereto were added 4-fluorophenol (3.2 g) and triphenylphosphine (7.5 g), then added dropwise diisopropyl azodicarboxylate (5.5 g). The mixture was stirred at room temperature overnight and the reaction solvent was concentrated in vacuo. The residue was purified by silica gel chromatography (eluent: hexane/ethyl acetate=3/1) to give Compound III (2.3 g). 
     Step (iii): 
     Compound III (2.3 g) was dissolved in chloroform (100 mL), and thereto was added 4N hydrochloric acid-dioxane solution (30 mL) and the mixture was stirred at room temperature for 6 hours. The reaction solvent was concentrated in vacuo, and thereto was added 2N sodium hydroxide solution and the mixture was extracted with chloroform. The organic layer was dried over sodium sulfate and then concentrated in vacuo to give Compound IV (1.8 g). 
     Step (iv): 
     1,1′-Thiocarbonyl diimidazole (2.0 g) was dissolved in THF (70 mL), and thereto was added Compound IV (1.8 g) and the mixture was stirred at room temperature for 1 hour. Then, thereto was added hydrazine monohydrate (10 mL) and the mixture was stirred under reflux for 1 hour. The mixture was concentrated in vacuo, and thereto was added water and the mixture was extractd with ethyl acetate. The organic layer was dried over sodium sulfate and concentrated in vacuo to give the titled Compound V (1.8 g). 
       1 H-NMR (CDCl 3 ) δ 1.24 (t, J=8.0 Hz, 2H), 2.03 (s, 3H), 4.10 (q, J=8.0 Hz, 2H), 4.20 (m, 1H), 6.56-6.66 (m, 4H), 7.12-7.14 (m, 2H) 
     Reference Example 7 
     4-Chloro-5-[cyclobutyl(2,2,2-trifluoroethyl)amino]-1-methyl-1H-pyrazole-3-carboxylic acid 
     
       
         
         
             
             
         
       
     
     Step (i): 
     Cyclobutylamine (7.1 g) was dissolved in dichloromethane (400 mL), and thereto was added anhydrous trifluoroacetic acid (17 mL) and the mixture was stirred at room temperature overnight. The mixture was concentrated in vacuo to give Compound II (10.5 g). 
     Step (ii): 
     To a solution of borane-dimethyl sulfide complex (21.5 g) in THF (300 mL) was added dropwise a solution of Compound II (10.5 g) in THF (50 mL) at 50° C., and the mixture was stirred at 50° C. overnight. Thereto was added methanol (150 mL) at 0° C., and the mixture was stirred at room temperature for 1 hour. Then, thereto was added 4N hydrochloric acid-ethanol solution (100 mL) and the mixture was stirred at room temperature for 1 hour. The reaction solution was concentrated in vacuo, and the residue was washed with ethyl acetate-hexane. The resulting white solid was filtered and dried in vacuo to give Compound III (10.9 g). 
     Step (iii): 
     Compound III (1.9 g) was dissolved in THF (20 mL), and thereto was added saturated sodium bicarbonate water (10 mL) and the mixture was stirred at room temperature for 30 minutes. Thereto was added dropwise a solution of 4-chlorophenyl chlorothioformate (2.3 g) in THF (5 mL) at 0° C., and the mixture was stirred at room temperature for 4 hours. Thereto was added brine, and the mixture was extracted with ethyl acetate. The organic layer was dried over sodium sulfate, concentrated in vacuo and dissolved in NMP (12 mL), and thereto was added hydrazine monohydrate (1.5 mL) and the mixture was stirred at room temperature for 1 hour. Thereto was added water, and then the mixture was extracted with ethyl acetate. The organic layer was washed with brine, and then dried over sodium sulfate and concentrated in vacuo. The residue was purified by silica gel chromatography (eluent: hexane/ethyl acetate=1/1) to give Compound IV (2.0 g). 
     Step (iv): 
     Compound IV (2.0 g) was dissolved in a mixed solvent of ethanol (20 mL) with THF (20 mL), and thereto were added sodium bicarbonate (765 mg) and ethyl bromopyruvate (1.8 g) and the mixture was stirred at 80° C. for 3 hours. Thereto was added 4N hydrochloric acid-ethanol solution (3 mL), and the mixture was stirred at 60° C. for 12 hours. The mixture was concentrated in vacuo, and then thereto was added saturated sodium bicarbonate water and the mixture was extracted with ethyl acetate. The organic layer was dried over sodium sulfate and concentrated in vacuo. The residue was purified by silica gel chromatography (eluent: hexane/ethyl acetate=1/1) to give Compound V (780 mg). 
     Step (v): 
     To a solution of sodium hydride (140 mg) in THF (10 mL) was added dropwise a solution of Compound V (778 mg) in THF (5 mL) at 0° C., and the mixture was stirred at room temperature for 1 hour. Then, thereto was slowly added methyl iodide (200 μL) at 0° C., and the mixture was stirred at room temperature overnight. Thereto was added water, and then the mixture was concentrated in vacuo. Thereto was added brine, and the mixture was extracted with ethyl acetate. The organic layer was dried over sodium sulfate and concentrated in vacuo. The residue was purified by silica gel chromatography (eluent: hexane/ethyl acetate=1/1) to give Compound VI (590 mg). 
     Step (vi): 
     Compound VI (340 mg) was dissolved in DMF (4.5 mL), and thereto was added N-chlorosuccinimide (178 mg) and the mixture was stirred at 60° C. for 4 hours. Thereto was added water, and then the mixture was extracted with ethyl acetate. The organic layer was washed with brine. The organic layer was dried over sodium sulfate and concentrated in vacuo. The residue was purified by silica gel chromatography (eluent: hexane/ethyl acetate=3/1) to give Compound VII (324 mg). 
     Step (vii): 
     Compound VII (320 mg) was dissolved in ethanol (4 mL), and thereto was added 5N sodium hydroxide solution (560 μL) and the mixture was stirred at room temperature overnight. The reaction solution was concentrated in vacuo, and then acidified by 1N hydrochloric acid and extracted with ethyl acetate. The organic layer was dried over sodium sulfate and concentrated in vacuo to give the titled Compound VIII (287 mg) as a white solid. 
       1 H-NMR (CDCl 3 ) δ 1.51-1.69 (m, 2H), 1.75-1.88 (m, 2H), 2.05-2.20 (m, 2H), 3.52-3.80 (m, 2H), 3.83 (s, 3H), 3.84-3.95 (m, 2H) 
     Reference Example 8 
     Ethyl 1,4-dimethyl-5-[methyl(2,2,2-trifluoroethyl)amino]-1H-pyrazole-3-carboxylate 
     
       
         
         
             
             
         
       
     
     Step (i): 
     To a solution of borane-dimethyl sulfide complex (23.9 g) in THF (300 mL) was added dropwise a solution of Compound I (10.0 g) in THF (50 mL) at 50° C. and the mixture was stirred at 50° C. overnight. Thereto was added methanol (150 mL) at 0° C., and the mixture was stirred at room temperature for 1 hour. Then, thereto was added 4N hydrochloric acid-ethanol solution (100 mL) and the mixture was stirred at room temperature for 1 hour. The reaction solution was concentrated in vacuo, and the residue was washed with ethyl acetate-hexane. The resulting white solid was filtered and dried in vacuo to give Compound II (10.0 g). 
     Step (ii): 
     Compound II (5.5 g) was dissolved in THF (40 mL), and thereto was added triethylamine (5.1 mL) and the mixture was stirred at room temperature for 30 minutes. The mixture was added to a solution of 1,1′-thiocarbonyl diimidazole (7.6 g) in THF (40 mL) and stirred at room temperature for 1 hour. Then, thereto was added hydrazine monohydrate (5.4 mL) and the mixture was stirred at room temperature for 1 hour. The mixture was concentrated in vacuo, and thereto was added brine and the mixture was extracted with ethyl acetate. The organic layer was dried over sodium sulfate and then concentrated in vacuo to give Compound III (6.1 g). 
     Step (iii): 
     Compound III (1.4 g) was dissolved in a mixed solvent of ethanol (20 mL) with THF (20 mL), and thereto were added sodium bicarbonate (670 mg) and ethyl 3-bromo ketobutanoate (2.2 g), and the resulting mixture was stirred at 70° C. for 3 hours. The reaction solution was concentrated in vacuo, and then thereto was added 4N hydrochloric acid-ethanol solution (5 mL) and the mixture was stirred at 90° C. overnight. The mixture was concentrated in vacuo, and then thereto was added saturated sodium bicarbonate water and the mixture was extracted with ethyl acetate. The organic layer was dried over sodium sulfate and concentrated in vacuo. The residue was purified by silica gel chromatography (eluent: hexane/ethyl acetate=2/1) to give Compound IV (1.1 g) as a white solid. 
     Step (iv): 
     To a solution of sodium hydride (155 mg) in THF (12 mL) was added dropwise a solution of Compound IV (854 mg) in THF (8 mL) at 0° C. and the mixture was stirred at room temperature for 1 hour. Then, thereto was slowly added methyl iodide (240 μL) at 0° C. and the mixture was stirred at room temperature for 3 hours. Thereto was added water, and then the mixture was concentrated in vacuo. Thereto was added brine, and the mixture was extracted with ethyl acetate. The organic layer was dried over sodium sulfate and concentrated in vacuo. The residue was purified by silica gel chromatography (eluent: hexane/ethyl acetate=2/1) to give the titled Compound V (445 mg). 
       1 H-NMR (CDCl 3 ) δ 1.40 (t, J=8.0 Hz, 3H), 2.24 (s, 3H), 2.93 (s, 3H), 3.52-3.61 (m, 2H), 3.80 (s, 3H), 4.39 (q, J=8.0 Hz, 2H) 
     Reference Example 9 
     N-(3-Methoxypropyl)cyclopropaneamine hydrochloride 
     
       
         
         
             
             
         
       
     
     Step (i): 
     To an ice-cooled mixed solution of cyclopropylamine (5.0 g), saturated sodium bicarbonate water (20 mL) and THF (200 mL) was added (Boc) 2 O (19.1 g), and the mixture was stirred at room temperature overnight. The organic layer was separated and the aqueous layer was extracted with ethyl acetate. The organic layer was dried over sodium sulfate and concentrated in vacuo to give Compound II (13.0 g). 
     Step (ii): 
     To an ice-cooled mixed solution of sodium hydride (1.7 g) and DMF (70 mL) was added dropwise a solution of Compound II (5.0 g) in DMF (5 mL). The mixture was stirred at room temperature for 1 hour and cooled to 0° C. again. Thereto was added dropwise 1-bromo-3-methoxypropane (7.3 g), and then the mixture was stirred at room temperature overnight. Thereto was added water, and the mixture was extracted with ethyl acetate. The organic layer was dried over sodium sulfate and concentrated in vacuo to give Compound III. 
     Step (iii): 
     Compound III obtained in Step (ii) was dissolved in dioxane (25 mL), and thereto was added 4N hydrochloric acid-dioxane solution (25 mL) and the mixture was stirred at room temperature for 4 hours. The mixture was concentrated in vacuo, and the residue was washed with dioxane and hexane to give the titled Compound IV (4.3 g). 
       1 H-NMR (CDCl 3 ) δ 0.67-0.74 (m, 2H), 0.82-0.86 (m, 2H), 1.82-1.88 (m, 2H), 2.64-2.69 (m, 1H), 2.97-3.05 (m, 2H), 3.23 (s, 3H), 3.33-3.39 (m, 2H), 8.92 (bs, 2H) 
     Reference Example 10 
     N-(2-Methoxyethyl)cyclopropaneamine hydrochloride 
     The titled compound was synthesized by using 1-bromo-2-methoxyethane in the similar manner to Reference Example 9. 
     
       
         
         
             
             
         
       
     
       1 H-NMR (CDCl 3 ) δ 0.68-0.73 (m, 2H), 0.82-0.86 (m, 2H), 2.63-2.69 (m, 1H), 3.13-3.16 (m, 2H), 3.29 (s, 3H), 3.59-3.62 (m, 2H), 9.06 (bs, 2H) 
     Reference Example 11 
     N-Cyclopropylcyclopropaneamine hydrochloride 
     
       
         
         
             
             
         
       
     
     Step (i): 
     To a solution of cyclopropylamine (3.0 g) and benzaldehyde (5.6 g) in methylene chloride (200 mL) was added NaBH(OAc) 3  (12.3 g), and the mixture was stirred at room temperature overnight. Thereto was added water, and the aqueous layer was extracted with chloroform. The organic layer was washed with brine, dried over sodium sulfate and concentrated in vacuo. The residue was dissolved in butyl formate (100 mL) and stirred at 150° C. overnight. The mixture was concentrated in vacuo, and the residue was purified by silica gel chromatography (eluent: hexane/ethyl acetate=3/2) to give Compound II (4.4 g). 
     Step (ii): 
     To a solution of ethylmagnesium bromide (0.96M solution in THF, 60 mL) in THF (170 mL) at −70° C. was added dropwise a solution of titanium tetraisopropoxide (9.3 g) in THF (20 mL) over 3 minutes, and the mixture was stirred for 2 minutes. Then, thereto was added dropwise a solution of Compound II (4.4 g) in THF (10 mL) over 3 minutes, and the mixture was stirred for 5 minutes. The mixture was warmed up to room temperature and stirred overnight. To the reaction solution were added saturated aqueous ammonium chloride solution (150 mL) and water (50 mL), and the mixture was stirred at room temperature for 3 hours. The white precipitate was filtered, and the filtrate was adjusted to pH 10 with 2M aqueous sodium hydroxide solution and extracted with ethyl acetate. The organic layer was washed with brine, dried over sodium sulfate and concentrated in vacuo. The residue was purified by silica gel chromatography (eluent: hexane/ethyl acetate=100/1) to give Compound III (2.7 g). 
     Step (iii): 
     A mixed solution of Compound III (2.7 g), methanol (60 mL), 4N hydrochloric acid-dioxane (7.5 mL) and 10% palladium-carbon (300 mg) was stirred at room temperature under hydrogen (3 atm) for 4.5 hours. The reaction solution was filtered through Celite®, and then the filtrate was concentrated to give the titled Compound IV (2.0 g). 
       1 H-NMR (CDCl 3 ) δ 0.71-0.78 (m, 4H), 0.80-0.91 (m, 4H), 2.73 (bs, 2H), 9.35 (bs, 2H) 
     Reference Example 12 
     N-Methyl-1-(1-phenylcyclobutyl)methaneamine hydrochloride 
     
       
         
         
             
             
         
       
     
     Step (i): 
     To a mixed solvent of toluene (135 mL) and water (10 mL) were added benzyl cyanide (5.9 g), potassium hydroxide (26.4 g), 1,3-dibromopropane (10.1 g) and tetrabutylammonium bromide (0.16 g), and the mixture was heated with stirring at 100° C. After dissolving potassium hydroxide, the reaction vessel was soaked in a water bath and vigorously stirred for 10 minutes. Then, the mixture was heated with stirring at 110° C. for 5 hours. Thereto was added water, and the aqueous layer was extracted with ethyl acetate. The organic layer was washed with brine, dried over sodium sulfate and concentrated in vacuo. The residue was purified by silica gel chromatography (eluent: hexane/ethyl acetate=20/1) to give Compound II (4.1 g). 
     Step (ii): 
     Lithium aluminum hydride (3.8 g) was suspended in THF (120 mL), and thereto was added dropwise a solution of Compound II in THF (5 mL) at room temperature. After completion of dropping, the reaction solution was heated at reflux for 5 hours. Thereto were added water (4 mL), aqueous sodium hydroxide solution (15%, 4 mL) and water (12 mL) under ice cooling, and the resulting precipitate was filtered off. The organic layer was concentrated in vacuo. To the residue was added water, and the mixture was extracted with ethyl acetate. The organic layer was washed with brine, dried over sodium sulfate and concentrated in vacuo. The residue was dissolved in ethyl formate (50 mL) and stirred at 100° C. overnight. The mixture was concentrated in vacuo, and then the residue was dissolved in THF (20 mL) and the solution was added dropwise to a suspension of lithium aluminum hydride (3.8 g) in THF (120 mL) at room temperature. After completion of dropping, the mixture was heated at reflux for 1 hour and stirred at room temperature overnight. Thereto was added sodium sulfate decahydrate until ceasing of gas generation, and then thereto was added anhydrous sodium sulfate. The precipitate was filtered off and the filtrate was concentrated in vacuo to give Compound III (4.7 g). 
       1 H-NMR (CDCl 3 ) δ 1.72-1.82 (m, 1H), 2.01-2.13 (m, 1H), 2.26-2.40 (m, 4H), 2.43-2.45 (m, 3H), 3.28-3.31 (m, 2H), 7.22-7.30 (m, 3H), 7.36-7.39 (m, 2H), 8.23 (bs, 2H) 
     Reference Example 13 
     Benzyl 4-[[3-(ethoxycarbonyl)-1H-pyrazol-5-yl] (methyl)amino]piperidine-1-carboxylate 
     
       
         
         
             
             
         
       
     
     Step (i): 
     To a solution of Compound I (7.1 g) in dichloromethane (400 mL) was added a solution of methylamine in THF (110 mL, 2M). After ice-cooling, thereto was added acetic acid (43 mL), then NaBH(OAc) 3  (35.3 g) in small portions. The mixture was stirred at room temperature overnight, and thereto were added water (200 mL) and potassium carbonate. After the completion of gas generation, the organic layer was separated. The aqueous layer was extracted with dichloromethane. The organic layer was combined to be dried over sodium sulfate and concentrated in vacuo to give Compound II (quantitative). 
     Step (ii): 
     To an ice-cooled mixture of Compound II obtained in Step (i), THF (200 mL), water (100 mL) and sodium bicarbonate (19.8 g) was added dropwise a solution of 4-chlorophenyl chlorothioformate (17.6 mL) in THF (100 mL), and the mixture was stirred at room temperature for 4 hours. The organic layer was separated, and then the aqueous layer was extracted with ethyl acetate. The organic layer was combined to be dried over sodium sulfate and concentrated in vacuo. To the residue was added DMF (200 mL) with ice cooling, and then thereto was added hydrazine monohydrate (12.6 mL) and the mixture was stirred at room temperature for 2 hours. Thereto was added brine, and then the mixture was extracted with ethyl acetate. The organic layer was washed with brine, and then dried over sodium sulfate and concentrated in vacuo. The residue was purified by silica gel chromatography (eluent: hexane/ethyl acetate=1/1 to chloroform/meththanol=10/1) to give Compound III (23.75 g). 
     Step (iii): 
     To an ice-cooled mixture of Compound III (23.75 g), sodium bicarbonate (12.37 g), 95% ethanol (250 mL) and THF (100 mL) was added ethyl bromopyruvate (11.6 mL). The mixture was stirred at room temperature for 30 minutes and then stirred at 90° C. After 2 hours, thereto was added acetic acid (150 mL) and the mixture was stirred at 125° C. while removing solvents with a Dean-Stark apparatus. The mixture was stirred overnight, and then cooled to room temperature and concentrated in vacuo. To the residue was added saturated sodium bicarbonate water, and the mixture was extracted with ethyl acetate. The organic layer was dried over sodium sulfate and concentrated in vacuo. The residue was purified by silica gel chromatography (eluent: hexane/ethyl acetate=1/1 to chloroform/ethanol=10/1) to give Compound III (14.8 g). 
       1 H-NMR (CDCl 3 ) δ 1.38 (t, J=4 Hz, 3H), 1.60-1.80 (m, 4H), 2.74 (s, 3H), 2.87 (m, 2H), 3.80 (m, 1H), 4.20-4.41 (m, 4H), 5.14 (s, 2H), 6.16 (s, 1H), 7.31-7.40 (m, 5H), 9.76 (br, 1H) 
     Reference Example 14 
     Benzyl 4-{[[3-(ethoxycarbonyl)-1H-pyrazol-5-yl](methyl)amino]methyl}piperidine-1-carboxylate 
     
       
         
         
             
             
         
       
     
     Step (i): 
     A solution of Compound I (5 g) in ethyl formate (8 mL) was stirred under reflux for 16 hours. The solution was concentrated in vacuo to give Compound II (quantitative). Repetitions of Step (i) gave enough amounts of Compound II for Step (ii). 
     Step (ii): 
     To an ice-cooled solution of Compound II (49.1 g) in THF (500 mL) was added dropwise borane-dimethyl sulfide complex (171 mL). After the completion of dropwise, the mixture was stirred at room temperature. After ceasing of gas generation, the mixture was stirred at 50° C. for 3 hours, and then stirred at room temperature overnight. To the ice-cooled reaction solution was added dropwise methanol (200 mL), and then the mixture was stirred at room temperature for 30 minutes and concentrated in vacuo. Then, to the residue was added water (100 mL), and the mixture was acidified with hydrochloric acid. The mixture was stirred for 2 hours, and then the resulting solid was filtered off. The filtrate was extracted with toluene twice. To the aqueous layer was added sodium hydroxide, and the mixture was adjusted to pH&gt;12 and extracted with dichloromethane three times. The organic layer was washed with brine, and then dried over sodium sulfate and concentrated in vacuo to give Compound III (40.94 g). 
     Step (iii): 
     To an ice-cooled mixture of Compound III (40.94 g), sodium bicarbonate (42.17 g), ethyl acetate (200 mL) and water (200 mL) was added dropwise a solution of Boc 2 O (73.1 g) in ethyl acetate (200 mL). After 4 hours, the organic layer was separated. The aqueous layer was extracted with ethyl acetate. The combined organic layer was washed with brine, and then dried over sodium sulfate and concentrated in vacuo. The residue was purified by silica gel chromatography (eluent: hexane/ethyl acetate=1/1 to 1/2) to give Compound IV. 
     Step (iv): 
     To Compound IV obtained in Step (iii) were added acetic acid (200 mL) and platinum oxide (PtO 2 , 5 g), and the mixture was stirred under 3-4 kgf/cm 2  of hydrogen atmosphere overnight. The reaction mixture was filtered through Celite® and washed with methanol. The filtrate was concentrated in vacuo, and then the residue was extracted with sodium hydroxide solution and dichloromethane. The organic layer was dried over sodium sulfate and concentrated in vacuo to give Compound V (66.93 g). 
     Step (v): 
     To an ice-cooled mixture of Compound V (66.93 g), sodium carbonate (62.1 g), toluene (200 mL) and water (300 mL) was added dropwise a solution of benzyloxycarbonyl chloride (55 g) in toluene (200 mL). The mixture was stirred overnight, and then a toluene layer was separated. The aqueous layer was extracted with ethyl acetate. The combined organic layer was dried over sodium sulfate and concentrated in vacuo. To the residue was added 4N hydrochloric acid-dioxane (80 mL), and the mixture was stirred at room temperature and concentrated in vacuo. Then, thereto were added diisopropylether and hexane, and the mixture was allowed to stand overnight at room temperature. The resulting solid was filtered and washed with diisopropylether and hexane, and then dried in vacuo to give Compound VI (68.56 g). 
     Step (vi): 
     To Compound VI (25 g) was added sodium hydroxide solution, and the mixture was stirred and then extracted with dichloromethane. The organic layer was dried over sodium sulfate and concentrated in vacuo. After obtaining the free form of Compound VI, thereto was added THF (100 mL). The solution was added dropwise to an ice-cooled solution of 1,1′-thiocarbonyl diimidazole (17.3 g) in THF (300 mL). After completion of dropping, the mixture was stirred at room temperature for 1.5 hours. The reaction solution was ice-cooled, and thereto was added hydrazine monohydrate (12.6 mL) and the mixture was stirred at room temperature overnight and concentrated in vacuo. Then, the residue was extracted with ethyl acetate and brine. The organic layer was washed with brine, and then dried over sodium sulfate and concentrated in vacuo. To the residue were added diisopropylether and hexane, and the mixture was stirred for 30 minutes, and then filtered and dried in vacuo to give Compound VII (27.43 g). 
     Step (vii): 
     To an ice-cooled mixed solution of Compound VII (27.43 g), sodium bicarbonate (13.7 g), 95% ethanol (400 mL) and THF (250 mL) was added ethyl bromopyruvate (12.8 mL). The mixture was stirred for 20 minutes and then stirred at 90° C. After 1 hour, thereto was added acetic acid (250 mL), and the mixture was stirred at 125° C. while removing solvents with a Dean-Stark apparatus. The mixture was stirred overnight, and then cooled to room temperature and concentrated in vacuo. To the residue was added saturated sodium bicarbonate water, and the mixture was extracted with ethyl acetate. The organic layer was dried over sodium sulfate and concentrated in vacuo. The residue was purified by silica gel chromatography (eluent: hexane/ethyl acetate=1/1) to give the titled Compound VIII (19.07 g). 
       1 H-NMR (CDCl 3 ) δ 1.19 (m, 2H), 1.40 (t, J=8 Hz, 3H), 1.72 (m, 2H), 1.92 (m, 1H), 2.78 (m, 2H), 2.94 (s, 3H), 3.13 (d, J=12 Hz, 2H), 4.22 (m, 2H), 4.37 (q, J=8 Hz, 2H), 5.14 (s, 2H), 6.09 (s, 1H), 7.32-7.42 (m, 5H), 9.80 (br, 1H) 
     Reference Example 15 
     Benzyl 4-{2-[[3-(ethoxycarbonyl-1H-pyrazol-5-yl](methyl)amino]ethyl}piperidine-1-carboxylate 
     4-(2-Aminoethyl)pyridine was treated in the similar manner to Reference Example 14 to give the following compounds. 
     
       
         
         
             
             
         
       
     
       1 H-NMR (CDCl 3 ) δ 1.18 (m, 2H), 1.38 (t, J=8 Hz, 3H), 1.48-1.56 (m, 3H), 1.69-1.75 (m, 2H), 2.77 (m, 2H), 2.87 (s, 3H), 3.28 (m, 2H), 4.17 (m, 2H), 4.37 (q, J=8 Hz, 2H), 5.13 (s, 2H), 6.11 (s, 1H), 7.30-7.37 (m, 5H), 9.73 (br, 1H) 
     Reference Example 16 
     Ethyl 5-[{(3R)-1-[(benzyloxy)carbonyl]pyrrolidin-3-yl}(methyl)amino]-1H-pyrazole-3-carboxylate 
     
       
         
         
             
             
         
       
     
     Step (i): 
     To an ice-cooled mixed solution of Compound I (25.6 g), toluene (200 mL), sodium carbonate (32.0 g) and water (300 mL) was added dropwise a solution of benzyloxycarbonyl chloride (25.8 g) in toluene (100 mL). The mixture was stirred overnight, and then thereto was added ethyl acetate and the mixture was stirred. Then, the reaction solution was filtered and the organic layer of the filtrate was separated. The aqueous layer was extracted with ethyl acetate. The combined organic layer was washed with water, and then dried over sodium sulfate and concentrated in vacuo. To the residue were added diisopropylether and hexane, and the mixture was stirred for 20 minutes and then the resulting solid was filtered and dried in vacuo to give Compound II (41.48 g). 
     Step (ii): 
     To an ice-cooled solution of Compound II (41.48 g) in DMF (300 mL) was added sodium hydride (5.7 g) in small portions. The mixture was stirred for 1.5 hours at room temperature, and then the reaction solution was ice-cooled. Thereto was added dropwise methyl iodide (9.8 mL), and then the mixture was stirred at room temperature overnight. The reaction solution was poured into citric acid solution, and the mixture was extracted with ethyl acetate. The organic layer was washed with brine, and then dried over sodium sulfate and concentrated in vacuo. The residue was purified by silica gel chromatography (eluent: hexane/ethyl acetate=1/1). Thereto was added 15% hydrochloric acid-ethanol (100 mL), and the mixture was allowed to stand for 3 days at room temperature. The mixture was concentrated in vacuo, and then thereto was added hydrochloric acid solution and the mixture was extracted with toluene. The toluene layer was extracted with 1N hydrochloric acid. The combined acidic aqueous layer was adjusted to pH&gt;14 with sodium hydroxide. The alkaline aqueous layer was extracted with dichloromethane, and the organic layer was dried over sodium sulfate and concentrated in vacuo to give Compound III (28.45 g). 
     Step (iii): 
     To an ice-cooled mixed solution of Compound III obtained in Step (ii), sodium bicarbonate (22.4 g), THF (100 mL) and water (100 mL) was added dropwise a solution of 4-chlorophenyl chlorothioformate (20 mL) in THF (100 mL), and the mixture was stirred at room temperature overnight. The organic layer was separated, and then the aqueous layer was extracted with ethyl acetate. The organic layer was combined, dried over sodium sulfate and concentrated in vacuo. Thereto was added DMF (200 mL), and the mixture was ice-cooled. Then, thereto was added hydrazine monohydrate (14.2 mL), and the mixture was stirred at room temperature for 2 hours. Thereto was added brine, and then the mixture was extracted with ethyl acetate. The organic layer was washed with brine, and then dried over sodium sulfate and concentrated in vacuo. The residue was purified by silica gel chromatography (eluent: hexane/ethyl acetate=1/1 to chlorofon methanol=10/1) to give Compound IV (34.74 g). 
     Step (iv): 
     To an ice-cooled mixed solution of Compound IV (34.74 g), sodium bicarbonate (18.9 g) and 95% ethanol (300 mL) was added ethyl bromopyruvate (17.7 mL). The mixture was stirred at room temperature for 20 minutes, and then stirred at 90° C. After 1.5 hours, thereto was added acetic acid (200 mL), and the mixture was stirred at 125° C. while removing solvents with a Dean-Stark apparatus. The mixture was stirred overnight, and then the mixture was cooled back to room temperature and concentrated in vacuo. To the residue was added saturated sodium bicarbonate water, and the mixture was extracted with ethyl acetate. The organic layer was dried over sodium sulfate and concentrated in vacuo. The residue was purified by silica gel chromatography (eluent: hexane/ethyl acetate=1/1 to chloroform/methanol=10/1) to give the titled Compound V (20.9 g) (49.8% yields). 
       1 H-NMR (CDCl 3 ) δ 1.39 (t, J=8 Hz, 3H), 2.09 (m, 2H), 2.82 (s, 3H), 3.34-3.48 (m, 2H), 3.56-3.75 (m, 2H), 4.37 (q, J=8 Hz, 2H), 4.45 (m, 1H), 5.15 (s, 2H), 6.20 (s, 1H), 7.31-7.41 (m, 5H), 9.85 (br, 1H) 
     Reference Example 17 
     Ethyl 5-[{(3S)-1-[(benzyloxy)carbonyl]pyrrolidin-3-yl}(methyl)amino]-1H-pyrazole-3-carboxylate 
     The titled compound was prepared in the similar manner to Reference Example 16. 
     
       
         
         
             
             
         
       
     
       1 H-NMR (CDCl 3 ) δ 1.39 (t, J=8 Hz, 3H), 2.09 (m, 2H), 2.82 (s, 3H), 3.33-3.49 (m, 2H), 3.56-3.76 (m, 2H), 4.37 (q, J=8 Hz, 2H), 4.45 (m, 1H), 5.15 (s, 2H), 6.20 (s, 1H), 7.31-7.41 (m, 5H), 9.85 (br, 1H) 
     Reference Example 18 
     Benzyl (3R)-3-[[3-(ethoxycarbonyl)-1H-pyrazol-5-yl](methyl)amino]piperidine-1-carboxylate 
     The titled compound was prepared in the similar manner to Reference Example 16. 
     
       
         
         
             
             
         
       
     
       1 H-NMR (CDCl 3 ) δ 1.35-1.39 (m, 3H), 1.51-1.74 (m, 4H), 1.78-1.81 (m, 1H), 1.92-1.95 (m, 1H), 2.65-2.73 (m, 1H), 2.82 (s, 3H), 3.57-3.64 (m, 1H), 4.12-4.27 (m, 2H), 4.33-4.38 (m, 2H), 5.13 (s, 2H), 6.17 (s, 1H), 7.29-7.39 (m, 5H) 
     Reference Example 19 
     Benzyl (3S)-3-[[3-(ethoxycarbonyl)-1H-pyrazol-5-yl](methyl)amino]piperidine-1-carboxylate 
     The titled compound was prepared in the similar manner to Reference Example 16. 
     
       
         
         
             
             
         
       
     
       1 H-NMR (CDCl 3 ) δ 1.35-1.39 (m, 3H), 1.51-1.74 (m, 4H), 1.78-1.81 (m, 1H), 1.92-1.95 (m, 1H), 2.65-2.73 (m, 1H), 2.82 (s, 3H), 3.57-3.64 (m, 1H), 4.12-4.27 (m, 2H), 4.33-4.38 (m, 2H), 5.13 (s, 2H), 6.17 (s, 1H), 7.29-7.39 (m, 5H) 
     Example 1 
     N-[(E)-5-(aminocarbonyl)-2-adamantyl]-5-(dimethylamino)-1-methyl-1H-pyrazole-3-carboxamide and 
     N-[(Z)-5-(aminocarbonyl)-2-adamantyl]-5-(dimethylamino)-1-methyl-1H-pyrazole-3-carboxamide 
     
       
         
         
             
             
         
       
     
     Step (i): 
     Compound I (153 mg) was dissolved in DMF (5 mL), and then thereto were added methyl 4-aminoadamantane-1-carboxylate hydrochloride (200 mg), WSC.HCl (217 mg), HOBt.H 2 O (146 mg) and triethylamine (158 μL), and the mixture was stirred at room temperature for 6 hours. Thereto was added water, and the mixture was extracted with ethyl acetate. The organic layer was dried over sodium sulfate and concentrated in vacuo. The residue was purified by preparative TLC (eluent: chloroform/methanol=10/1) to give Compound II (82 mg). 
     Step (ii): 
     Compound II (72 mg) was dissolved in methanol (3 ml), and then thereto was added 2N sodium hydroxide solution (1 mL) and the mixture was stirred at room temperature overnight and concentrated in vacuo. Then, the mixture was acidified by diluted hydrochloric acid, and then extracted with ethyl acetate. The organic layer was dried over sodium sulfate and concentrated in vacuo. The residue was dissolved in DMF (5 ml), and thereto were added ammonium chloride (13 mg), WSCI.HCl (45 mg), HOBt.H 2 O (32 mg) and triethylamine (55 μL) and the mixture was stirred at room temperature overnight. Thereto was added water, and then the mixture was extracted with ethyl acetate. The organic layer was dried over sodium sulfate and concentrated in vacuo. The residue was purified by preparative TLC (eluent: chloroform/methanol=10/1) to give Compound III (16 mg) as a high-polar ingredient and Compound IV (4.9 mg) as a low-polar one. The structures were determined by X-ray crystallographic analysis. 
     N-[(E)-5-(Aminocarbonyl)-2-adamantyl]-5-(dimethylamino)-1-methyl-1H-pyrazole-3-carboxamide 
     A high-polar ingredient 
       1 H-NMR (CDCl 3 ) δ 1.63-1.68 (m, 3H), 1.93-1.97 (m, 4H), 2.00-2.08 (m, 4H), 2.08-2.16 (m, 2H), 2.69 (s, 6H), 3.75 (s, 3H), 4.19-4.21 (m, 1H), 5.27 (s, 1H), 5.62 (s, 1H), 6.31 (s, 1H), 7.17 (m, 1H) 
     N-[(Z)-5-(Aminocarbonyl)-2-adamantyl]-5-(dimethylamino)-1-methyl-1H-pyrazole-3-carboxamide 
     A low-polar ingredient 
       1 H-NMR (CDCl 3 ) δ 1.55-1.68 (m, 4H), 1.77-1.84 (m, 3H), 1.93-1.97 (m, 3H), 2.08-2.10 (m, 2H), 2.20 (m, 1H), 2.70 (s, 6H), 3.75 (s, 3H), 4.15 (m, 1H), 5.24 (s, 1H), 5.65 (s, 1H), 6.32 (m, 1H), 7.13 (m, 1H) 
     Example 2 
     5-[Cyclopropyl(3-methoxybenzyl)amino]-N-[(E)-5-hydroxy-2-adamantyl]-1-methyl-1H-pyrazole-3-carboxamide 
     
       
         
         
             
             
         
       
     
     Step (i): 
     Compound I (24 mg) was dissolved in methanol (5 mL), and then thereto was added 2N sodium hydroxide solution (500 μL) and the mixture was stirred at room temperature overnight. The reaction solution was concentrated in vacuo, and then acidified by 1N hydrochloric acid and extracted with ethyl acetate. The organic layer was dried over sodium sulfate and concentrated in vacuo to give Compound II (14 mg). 
     Step (ii): 
     Compound II (14 mg) was dissolved in DMF (2 mL), and then thereto were added (E)-4-aminoadamantan-1-ol hydrochloride (14 mg), WSCI.HCl (86 mg), HOBt.H 2 O (60 mg) and triethylamine (19 μL), and the mixture was stirred at room temperature overnight. Thereto was added water, and then the mixture was extracted with ethyl acetate. The organic layer was dried over sodium sulfate and concentrated in vacuo. The residue was purified by preparative TLC (eluent: chloroform/methanol=10/1) to give Compound III (21 mg). 
       1 H-NMR (CDCl 3 ) δ 0.44-0.46 (m, 2H), 0.56-0.57 (m, 2H), 1.52-1.55 (m, 2H), 1.64 (m, 1H), 1.78-1.80 (m, 4H), 1.85-1.95 (m, 4H), 2.19-2.22 (m, 3H), 2.44 (m, 1H), 3.55 (s, 3H), 3.75 (s, 3H), 4.10 (s, 2H), 4.17 (m, 1H), 6.67 (s, 1H), 6.76 (m, 1H), 6.80 (m, 1H), 7.10 (m, 1H), 7.19 (m, 1H) 
     The following compounds were synthesized in the similar manner to Example 2. 
     Example 3 
     5-[Cyclopropyl(4-methoxybenzyl)amino]-N-[(E)-5-hydroxy-2-adamantyl]-1-methyl-1H-pyrazole-3-carboxamide 
     
       
         
         
             
             
         
       
     
       1 H-NMR (CDCl 3 ) δ 0.42-0.43 (m, 2H), 0.55-0.57 (m, 2H), 1.52-1.60 (m, 3H), 1.78-1.80 (m, 4H), 1.86-1.96 (m, 4H), 2.19-2.22 (m, 3H), 2.39 (m, 1H), 3.52 (s, 3H), 3.79 (s, 3H), 4.06 (s, 2H), 4.18 (m, 1H), 6.45 (s, 1H), 6.78-6.81 (m, 2H), 7.01-7.05 (m, 2H), 7.11 (m, 1H) 
     Example 4 
     N-[(E)-5-Hydroxy-2-adamantyl]-1-methyl-5-[methyl(2-phenoxyethyl)amino]-1H-pyrazole-3-carboxamide 
     
       
         
         
             
             
         
       
     
       1 H-NMR (CDCl 3 ) δ 1.52-1.54 (m, 3H), 1.78-1.80 (m, 4H), 1.85-1.88 (m, 2H), 1.92-1.95 (m, 2H), 2.18-2.22 (m, 3H), 2.78 (s, 3H), 3.28 (t, 5.4 Hz, 2H), 3.75 (s, 3H), 4.04 (t, 5.4 Hz, 2H), 4.16-4.18 (m, 1H), 6.44 (s, 1H), 6.85-6.87 (m, 2H), 6.93-6.97 (m, 1H), 7.09-7.11 (m, 1H), 7.27-7.29 (m, 2H) 
     Example 5 
     5-[[4-(4-Fluorophenoxy)benzyl](methyl)amino]-N-[(E)-5-hydroxy-2-adamantyl]-1-methyl-1H-pyrazole-3-carboxamide 
     
       
         
         
             
             
         
       
     
       1 H-NMR (CDCl 3 ) δ 1.52-1.55 (m, 3H), 1.78-1.80 (m, 4H), 1.84-1.88 (m, 2H), 1.92-1.95 (m, 2H), 2.19-2.21 (m, 3H), 2.61 (s, 3H), 3.74 (s, 3H), 3.96 (s, 2H), 4.16-4.18 (m, 1H), 6.40 (s, 1H), 6.90-6.92 (m, 2H), 6.96-7.06 (m, 4H), 7.09-7.11 (m, 1H), 7.22-7.24 (m, 2H) 
     Example 6 
     N-[(E)-5-Hydroxy-2-adamantyl]-1-methyl-5-{methyl[3-(methylsulfonyl)benzyl]amino}-1H-pyrazole-3-carboxamide 
     
       
         
         
             
             
         
       
     
       1 H-NMR (CDCl 3 ) δ 1.50-1.58 (m, 2H), 1.75-1.94 (m, 9H), 2.20 (m, 3H), 2.64 (s, 3H), 3.06 (s, 3H), 3.73 (s, 3H), 4.12 (s, 2H), 4.13-4.19 (m, 1H), 6.39 (s, 1H), 7.08-7.15 (m, 1H), 7.51-7.63 (m, 2H), 7.74-7.90 (m, 2H) 
     Example 7 
     N-[(E)-5-Carbamoyladamantan-2-yl]-1-methyl-5-[methyl(propyl)amino]-1H-pyrazole-3-carboxamide 
     
       
         
         
             
             
         
       
     
       1 H-NMR (CDCl 3 ) δ 0.82 (t, J=7.1 Hz, 3H), 1.39-1.47 (m, 2H), 1.54-1.57 (m, 2H), 1.70 (m, 1H), 1.85-1.89 (m, 4H), 1.93-1.97 (m, 4H), 1.99-2.10 (m, 2H), 2.57 (s, 3H), 2.71-2.78 (m, 2H), 3.66 (s, 3H), 4.12 (m, 1H), 5.37 (bs, 1H), 5.60 (bs, 1H), 6.28 (s, 1H), 7.10 (m, 1H) 
     Example 8 
     N-[(E)-5-Carbamoyladamantan-2-yl]-5-[isopropyl(methyl)amino]-1-methyl-1H-pyrazole-3-carboxamide 
     
       
         
         
             
             
         
       
     
       1 H-NMR (CDCl 3 ) δ 1.10 (d, J=6.5 Hz, 6H), 1.54 (m, 1H), 1.63-1.66 (m, 2H), 1.94-1.99 (m, 4H), 2.02-2.08 (m, 4H), 2.18-2.20 (m, 2H), 2.58 (s, 3H), 3.17 (sept, J=6.5 Hz, 1H), 3.73 (s, 3H), 4.21 (m, 1H), 5.20 (bs, 1H), 5.59 (bs, 1H), 6.42 (s, 1H), 7.01 (m, 1H) 
     Example 9 
     N-[(E)-5-Carbamoyladamantan-2-yl]-5-[ethyl(methyl)amino]-1-methyl-1H-pyrazole-3-carboxamide 
     
       
         
         
             
             
         
       
     
       1 H-NMR (CDCl 3 ) δ 1.09 (t, J=7.2 Hz, 3H), 1.62-1.67 (m, 3H), 1.93-1.98 (m, 4H), 2.02-2.08 (m, 4H), 2.18-2.20 (m, 2H), 2.65 (s, 3H), 2.92 (q, J=7.2 Hz, 2H), 3.73 (s, 3H), 4.20 (m, 1H), 5.33 (bs, 1H), 5.63 (bs, 1H), 6.36 (s, 1H), 7.16 (m, 1H) 
     Example 10 
     N-[(E)-5-Carbamoyladamantan-2-yl]-5-[isobutyl(methyl)amino]-1-methyl-1H-pyrazole-3-carboxamide 
     
       
         
         
             
             
         
       
     
       1 H-NMR (CDCl 3 ) δ 0.90 (m, 6H), 1.57-1.68 (m, 2H), 1.78 (m, 1H), 1.90-2.09 (m, 9H), 2.13-2.21 (m, 2H), 2.60-2.64 (m, 5H), 3.73 (s, 3H), 4.17-4.23 (m, 1H), 5.32 (bs, 1H), 5.63 (bs, 1H), 6.35 (s, 1H), 7.14-7.20 (m, 1H) 
     Example 11 
     N-[(E)-5-Carbamoyladamantan-2-yl]-4-chloro-5-(dimethylamino)-1-methyl-1H-pyrazole-3-carboxamide 
     
       
         
         
             
             
         
       
     
       1 H-NMR (CDCl 3 ) δ 1.53-1.56 (m, 2H), 1.63-1.66 (m, 2H), 1.90-1.94 (m, 3H), 2.03-2.07 (m, 4H), 2.18-2.22 (m, 2H), 2.86 (s, 6H), 3.73 (s, 3H), 4.22 (m, 1H), 5.19 (bs, 1H), 5.59 (bs, 1H), 7.08 (m, 1H) 
     Example 12 
     N-[(E)-5-Hydroxyadamantan-2-yl]-1-methyl-5-{methyl[4-(methylsulfonyl)benzyl]amino}-1H-pyrazole-3-carboxamide 
     
       
         
         
             
             
         
       
     
       1 H-NMR (CDCl 3 ) δ 1.47-1.58 (m, 2H), 1.73-1.96 (m, 9H), 2.13-2.25 (m, 3H), 2.65 (s, 3H), 3.05 (s, 3H), 3.75 (s, 3H), 4.11 (s, 2H), 4.13-4.18 (m, 1H), 6.41 (s, 1H), 7.08-7.13 (m, 1H), 7.49-7.53 (m, 2H), 7.88-7.91 (m, 2H) 
     Example 13 
     N-[(E)-5-Carbamoyladamantan-2-yl]-5-[(cyclopropylmethyl)(propyl)amino]-1-methyl-1H-pyrazole-3-carboxamide 
     
       
         
         
             
             
         
       
     
       1 H-NMR (CDCl 3 ) δ 0.02-0.05 (m, 2H), 0.40-0.45 (m, 2H), 0.81-0.88 (m, 1H), 0.86 (t, J=7.4 Hz, 3H), 1.36-1.43 (m, 2H), 1.60-1.65 (m, 2H), 1.93-2.18 (m, 11H), 2.73 (d, J=6.8 Hz, 2H), 2.91 (t, J=7.4 Hz, 2H), 3.76 (s, 3H), 4.19-4.21 (m, 1H), 5.16 (bs, 1H), 5.58 (bs, 1H), 6.47 (s, 1H), 7.19-7.21 (m, 1H) 
     Example 14 
     N-[(E)-5-Carbamoyladamantan-2-yl]-5-[(2-methoxyethyl)(methyl)amino]-1-methyl-1H-pyrazole-3-carboxamide 
     
       
         
         
             
             
         
       
     
       1 H-NMR (CDCl 3 ) δ 1.58-1.66 (m, 2H), 1.90-2.09 (m, 9H), 2.13-2.20 (m, 2H), 2.72 (s, 3H), 3.05 (m, 2H), 3.34 (s, 3H), 3.46 (m, 2H), 3.75 (s, 3H), 4.16-4.23 (m, 1H), 5.29 (bs, 1H), 5.62 (bs, 1H), 6.38 (s, 1H), 7.14-7.20 (m, 1H) 
     Example 15 
     N-[(E)-5-Carbamoyladamantan-2-yl]-5-[(cyclopropylmethyl)(methyl)amino]-1-methyl-1H-pyrazole-3-carboxamide 
     
       
         
         
             
             
         
       
     
       1 H-NMR (CDCl 3 ) δ 0.08-0.11 (m, 2H), 0.43-0.53 (m, 2H), 0.85-0.95 (m, 1H), 1.58-1.68 (m, 2H), 1.90-2.09 (m, 9H), 2.13-2.20 (m, 2H), 2.68-2.74 (m, 5H), 3.74 (s, 3H), 4.15-4.23 (m, 1H), 5.25 (bs, 1H), 5.60 (bs, 1H), 6.37 (s, 1H), 7.14-7.20 (m, 1H) 
     Example 16 
     5-(Cyclopropyl{[1-(3,3,3-trifluoropropyl)piperidin-4-yl]methyl}amino)-N-[(E)-5-hydroxyadamantan-2-yl]-1-methyl-1H-pyrazole-3-carboxamide 
     
       
         
         
             
             
         
       
     
     Step (i): 
     Compound I (50 mg) was dissolved in dichloromethane (1 mL), and then thereto were added 3,3,3-trifluoro propionaldehyde (23 mg) and acetic acid (100 μL). The mixture was stirred at room temperature for 1.5 hours, and then thereto was added NaBH(OAc) 3  (60 mg) and the mixture was stirred at room temperature overnight. Thereto was added water, and the mixture was extracted with chloroform. The organic layer was washed with saturated sodium bicarbonate water. The organic layer was dried over sodium sulfate and concentrated in vacuo. The residue was purified by preparative TLC (eluent: chloroform/methanol=10/1) to give the titled Compound II (48 mg). 
       1 H-NMR (CDCl 3 ) δ 0.35-0.44 (m, 2H), 0.53-0.61 (m, 2H), 1.13-1.28 (m, 2H), 1.46-1.98 (m, 16H), 2.16-2.35 (m, 5H), 2.45 (m, 1H), 2.52-2.59 (m, 2H), 2.81-2.92 (m, 4H), 3.68 (s, 3H), 4.13-4.20 (m, 1H), 6.43 (s, 1H), 7.09-7.14 (m, 1H) 
     Example 17 
     5-(Cyclopropyl{[1-(2-methoxyethyl)piperidin-4-yl]methyl}amino)-N-[(E)-5-hydroxyadamantan-2-yl]-1-methyl-1H-pyrazole-3-carboxamide 
     
       
         
         
             
             
         
       
     
       1 H-NMR (CDCl 3 ) δ 0.36-0.45 (m, 2H), 0.53-0.61 (m, 2H), 1.20-1.33 (m, 2H), 1.46-1.72 (m, 6H), 1.74-1.98 (m, 10H), 2.15-2.26 (m, 3H), 2.45 (m, 1H), 2.50-2.58 (m, 2H), 2.85-2.97 (m, 4H), 3.34 (s, 3H), 3.49 (m, 2H), 3.67 (s, 3H), 4.14-4.20 (m, 1H), 6.43 (s, 1H), 7.09-7.14 (m, 1H) 
     Example 18 
     N-[(E)-5-Carbamoyladamantan-2-yl]-5-(diethylamino)-1-methyl-1H-pyrazole-3-carboxamide 
     
       
         
         
             
             
         
       
     
       1 H-NMR (CDCl 3 ) δ 1.00 (t, J=7.1 Hz, 6H), 1.62-1.65 (m, 2H), 1.93-2.18 (m, 11H), 2.93 (q, J=7.1 Hz, 4H), 3.73 (s, 3H), 4.19-4.21 (m, 1H), 5.17 (bs, 1H), 5.58 (bs, 1H), 6.44 (s, 1H), 7.19-7.21 (m, 1H) 
     Example 19 
     N-[(E)-5-Carbamoyladamantan-2-yl]-5-[cyclobutyl(methyl)amino]-1-methyl-1H-pyrazole-3-carboxamide 
     
       
         
         
             
             
         
       
     
       1 H-NMR (CDCl 3 ) δ 1.40-1.70 (m, 4H), 1.77-1.87 (m, 2H), 1.93-2.11 (m, 11H), 2.17-2.18 (m, 2H), 2.52 (s, 3H), 3.48-3.56 (m, 1H), 3.73 (s, 3H), 4.19-4.21 (m, 1H), 5.19 (bs, 1H), 5.58 (bs, 1H), 6.33 (s, 1H), 7.17-7.19 (m, 1H) 
     Example 20 
     5-[Cyclopropyl(piperidin-4-ylmethyl)amino]-N-[(E)-5-hydroxyadamantan-2-yl]-1-methyl-1H-pyrazole-3-carboxamide 
     
       
         
         
             
             
         
       
     
       1 H-NMR (CDCl 3 ) δ 0.40-0.45 (m, 2H), 0.55-0.61 (m, 2H), 1.50-1.67 (m, 4H), 1.68-1.97 (m, 13H), 2.15-2.26 (m, 3H), 2.48 (m, 1H), 2.72-2.83 (m, 2H), 2.94-2.99 (m, 2H), 3.41-3.46 (m, 2H), 3.69 (s, 3H), 4.13-4.19 (m, 1H), 6.43 (s, 1H), 7.09-7.15 (m, 1H) 
     Example 21 
     5-{[(1-Acetylpiperidin-4-yl)methyl](cyclopropyl)amino}-N-[(E)-5-hydroxyadamantan-2-yl]-1-methyl-1H-pyrazole-3-carboxamide 
     
       
         
         
             
             
         
       
     
       1 H-NMR (CDCl 3 ) δ 0.38-0.45 (m, 2H), 0.54-0.61 (m, 2H), 1.01-1.15 (m, 2H), 1.41-1.65 (m, 5H), 1.67-1.82 (m, 5H), 1.83-1.97 (m, 4H), 2.06 (s, 3H), 2.15-2.28 (m, 3H), 2.42-2.53 (m, 2H), 2.86-2.31 (m, 3H), 3.69 (s, 3H), 3.73-3.81 (m, 1H), 4.13-4.21 (m, 1H), 4.53-4.62 (m, 1H), 6.44 (s, 1H), 7.09-7.15 (m, 1H) 
     Example 22 
     N-[(E)-5-(Aminocarbonyl)-2-adamantyl]-4-chloro-5-[[1-(4-methoxyphenyl)cyclopropyl](methyl)amino]-1-methyl-1H-pyrazole-3-carboxamide 
     
       
         
         
             
             
         
       
       
         
         
             
             
         
       
     
     Step (i): 
     1-(4-Methoxyphenyl)-cyclopropanecarboxylic acid (5.0 g) was dissolved in toluene (80 mL), and then thereto were added triethylamine (3.8 mL) and diphenyl phosphoryl azide (5.9 mL), and the mixture was stirred at 100° C. for 5 hours. The reaction solvent was concentrated in vacuo, and then dissolved in THF (80 ml). Then, thereto was added 2N sodium hydroxide solution (30 mL), and the mixture was stirred at room temperature for 2 hours. The mixture was concentrated in vacuo, and then thereto was added 1N hydrochloric acid and the mixture was extracted with ethyl acetate. The aqueous layer was basified by sodium hydroxide solution and extracted with chloroform. The organic layer was dried over sodium sulfate and concentrated in vacuo to give Compound II (2.9 g). 
     Step (ii): 
     Compound II (2.9 g) was dissolved in ethyl formate (30 mL) and stirred in a sealed tube at 90° C. for 3 days, and the reaction solvent was concentrated in vacuo. The residue was dissolved in THF (10 mL) and added dropwise to a solution of lithium aluminum hydride (2.7 g) in THF (80 mL). The mixture was stirred at 80° C. for 3 hours, and then thereto were added water (3 mL), 15% sodium hydroxide solution (3 mL) and water (9 mL) at 0° C. in sequence. The reaction solution was filtered through Celite®. The filtrate was concentrated in vacuo to give Compound III (2.5 g). 
     Step (iii): 
     4-Chlorophenyl chlorothioformate (2.9 g) was dissolved in THF (30 mL), and thereto were added triethylamine (2.1 mL) and Compound III (2.5 g) at 0° C. and the mixture was stirred at room temperature for 2 hours. The reaction solution was concentrated in vacuo, and then thereto was added water and the mixture was extracted with ethyl acetate. The organic layer was washed with brine, dried over sodium sulfate, and then concentrated in vacuo. The residue was dissolved in NMP (30 mL), and then thereto was added hydrazine monohydrate (3.4 mL) and the mixture was stirred at 70° C. for 6 hours. Thereto was added water, and the mixture was extracted with ethyl acetate. The organic layer was washed with brine, and then dried over sodium sulfate and concentrated in vacuo. The residue was purified by silica gel chromatography (eluent: hexane/ethyl acetate=7/3) to give Compound IV (2.1 g). 
     Step (iv): 
     Compound IV (2.1 g) was dissolved in a mixed solvent of ethanol (25 mL) and THF (25 mL), and thereto were added sodium bicarbonate (690 mg) and ethyl bromopyruvate (1.2 mL) and the mixture was stirred at 70° C. for 4 hours. The reaction solution was concentrated in vacuo, and then thereto was added acetic acid (50 mL) and the mixture was stirred at 80° C. for 5 hours and concentrated in vacuo. Then, thereto was added saturated sodium bicarbonate water, and the mixture was extracted with ethyl acetate. The organic layer was dried over sodium sulfate and concentrated in vacuo. The residue was purified by silica gel chromatography (eluent: hexane/ethyl acetate=2/1) to give Compound V (1.6 g). 
     Step (v): 
     To a solution of sodium hydride (250 mg) in THF (20 mL) was added dropwise a solution of Compound V (1.6 g) in THF (5 mL) at 0° C., and the mixture was stirred at room temperature for 1 hour. Then, thereto was slowly added methyl iodide (380 μL) at 0° C., and the mixture was stirred at room temperature overnight. Then, thereto was added water, and then the mixture was concentrated in vacuo. Thereto was added saturated sodium bicarbonate water, and the mixture was extracted with chloroform. The organic layer was dried over sodium sulfate and concentrated in vacuo. The residue was purified by silica gel chromatography (eluent: hexane/ethyl acetate=2/1) to give Compound VI (1.2 g). 
     Step (vi): 
     Compound VI (599 mg) was dissolved in DMF (10 mL), and then thereto was added N-chlorosuccinimide (267 mg) in small portions, and the mixture was stirred at room temperature overnight. Then, thereto was added water, and then the mixture was extracted with ethyl acetate. The organic layer was sequentially washed with saturated sodium bicarbonate water and brine. The organic layer was dried over sodium sulfate and concentrated in vacuo. The residue was purified by silica gel chromatography (eluent: hexane/ethyl acetate=3/1) to give Compound VII (530 mg). 
     Step (vii): 
     Compound VII (530 mg) was dissolved in ethanol (15 mL), and then thereto was added 2N lithium hydroxide solution (2.2 mL), and the mixture was stirred at room temperature overnight. The reaction solution was concentrated in vacuo, and then acidified by 1N hydrochloric acid and extracted with chloroform. The organic layer was dried over sodium sulfate and concentrated in vacuo to give Compound VIII (490 mg). 
     Step (viii): 
     Compound VIII (80 mg) was dissolved in DMF (1.5 mL), and then thereto were added methyl (E)-4-aminoadamantane-1-carboxylate (50 mg), WSCI.HCl (69 mg), HOBt.H 2 O (49 mg) and triethylamine (100 μL), and the mixture was stirred at room temperature overnight. Then, thereto was added water, and then the mixture was extracted with ethyl acetate. The organic layer was sequentially washed with saturated sodium bicarbonate water, 1N hydrochloric acid and brine. The organic layer was dried over sodium sulfate and concentrated in vacuo. The residue was dissolved in methanol (1.5 mL), and then thereto was added 2N lithium hydroxide solution (400 μL) and the mixture was stirred at room temperature overnight. The reaction solution was concentrated in vacuo, and then acidified by 1N hydrochloric acid and extracted with ethyl acetate. The organic layer was dried over sodium sulfate and concentrated in vacuo. The residue was dissolved in DMF (1.5 mL), and then thereto were added ammonium chloride (134 mg), WSCI.HCl (69 mg), HOBt.H 2 O (49 mg) and triethylamine (460 μL) and the mixture was stirred at room temperature overnight. Then, thereto was added water, and then the mixture was extracted with ethyl acetate. The organic layer was sequentially washed with saturated sodium bicarbonate water, 1N hydrochloric acid and brine. The organic layer was dried over sodium sulfate and concentrated in vacuo. The residue was purified by preparative TLC (eluent: chlorofol methanol=10/1) to give the titled Compound IX (101 mg) as a white solid. 
       1 H-NMR (CDCl 3 ) δ 0.98-1.01 (m, 2H), 1.10-1.13 (m, 2H), 1.63-1.66 (m, 2H), 1.89-2.19 (m, 11H), 2.96 (s, 3H), 3.61 (s, 3H), 3.81 (s, 3H), 4.23-4.25 (m, 1H), 6.11 (bs, 1H), 6.64 (bs, 1H), 6.85-6.90 (m, 2H), 7.13-7.15 (m, 1H), 7.22-7.25 (m, 2H) 
     The following compounds were obtained in the similar manner. 
     
       
         
           
               
             
               
                   
               
             
            
               
                 [Chemical Formula 68] 
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
               
            
           
           
               
               
               
            
               
                 Example No. 
                 R D   
                 A 
               
               
                   
               
               
                 23 
                 H 
                 CONH 2   
               
               
                 24 
                 Cl 
                 OH 
               
               
                 25 
                 H 
                 OH 
               
               
                   
               
            
           
         
       
     
     Example 23 
       1 H-NMR (CDCl 3 ) δ 1.03-1.11 (m, 4H), 1.61-2.18 (m, 13H), 2.82 (s, 3H), 3.71 (s, 3H), 3.81 (s, 3H), 4.19-4.21 (m, 1H), 5.24 (bs, 1H), 5.61 (bs, 1H), 6.24 (s, 1H), 6.87-6.91 (m, 2H), 7.17-7.20 (m, 2H), 7.45-7.47 (m, 1H) 
     Example 24 
       1 H-NMR (CDCl 3 ) δ 0.98-1.01 (m, 2H), 1.11-1.14 (m, 2H), 1.52-1.55 (m, 2H), 1.77-1.85 (m, 7H), 1.91-1.94 (m, 2H), 2.18-2.22 (m, 3H), 2.97 (s, 3H), 3.59 (s, 3H), 3.81 (s, 3H), 4.18-4.20 (m, 1H), 6.87-6.90 (m, 2H), 7.05-7.06 (m, 1H), 7.23-7.25 (m, 2H) 
     Example 25 
       1 H-NMR (CDCl 3 ) δ 0.97-1.04 (m, 4H), 1.61-1.64 (m, 3H), 1.69-1.81 (m, 6H), 1.93-1.96 (m, 2H), 2.15-2.16 (m, 1H), 2.27 (bs, 2H), 2.75 (s, 3H), 3.65 (s, 3H), 3.81 (s, 3H), 4.08-4.10 (m, 1H), 6.21 (s, 1H), 6.87-6.91 (m, 2H), 7.18-7.25 (m, 3H) 
     Example 26 
     N-[(E)-5-(Aminocarbonyl)-2-adamantyl]-4-fluoro-5-[isopropylmethyl)amino]-1-methyl-1H-pyrazole-3-carboxamide 
     
       
         
         
             
             
         
       
     
     Step (i): 
     To a solution of Compound I (200 mg) in DMF (15 mL) was added saturated sodium bicarbonate water (3 mL), and then thereto was added 1-chloromethyl-4-fluoro-1,4-diazoniabicyclo[2.2.2.]octane bis(tetrafluoroborate) (638 mg) in small portions and the mixture was stirred at room temperature for 3 hours. Then, thereto was added water, and then the mixture was extracted with ethyl acetate. The organic layer was dried over sodium sulfate and concentrated in vacuo. The residue was purified by silica gel chromatography (eluent: hexane/ethyl acetate=3/1) to give Compound II (64 mg). 
     Step (ii): 
     Compound II (65 mg) was dissolved in ethanol (1.5 mL), and then thereto was added 2N lithium hydroxide solution (380 μL) and the mixture was stirred at room temperature overnight. The reaction solution was concentrated in vacuo, and then acidified by 1N hydrochloric acid and extracted with ethyl acetate. The organic layer was dried over sodium sulfate and concentrated in vacuo to give Compound III (45 mg). 
     Step (iii): 
     Compound III (23 mg) was dissolved in DMF (0.5 mL), and then thereto were added methyl (E)-4-aminoadamantane-1-carboxylate (31 mg), WSCI.HCl (29 mg), HOBt.H 2 O (20 mg) and triethylamine (40 μL), and the mixture was stirred at room temperature overnight. Then, thereto was added water, and then the mixture was extracted with ethyl acetate. The organic layer was sequentially washed with saturated sodium bicarbonate water, 1N hydrochloric acid and brine. The organic layer was dried over sodium sulfate and concentrated in vacuo. The residue was dissolved in methanol (0.5 mL), and then thereto was added 2N lithium hydroxide solution (140 μL) and the mixture was stirred at room temperature overnight. The reaction solution was concentrated in vacuo, and then acidified by 1N hydrochloric acid and extracted with ethyl acetate. The organic layer was dried over sodium sulfate and concentrated in vacuo. The residue was dissolved in DMF (0.5 mL), and then thereto were added ammonium chloride (53 mg), WSCI.HCl (28 mg), HOBt.H 2 O (20 mg) and triethylamine (130 μL) and the mixture was stirred at room temperature overnight. Then, thereto was added water, and then the mixture was extracted with ethyl acetate. The organic layer was sequentially washed with saturated sodium bicarbonate water, 1N hydrochloric acid and brine. The organic layer was dried over sodium sulfate and concentrated in vacuo. The residue was purified by preparative TLC (eluent: chloroform/methanol=10/1) to give the titled Compound IV (22 mg) as a white solid. 
       1 H-NMR (CDCl 3 ) δ 1.10-1.12 (m, 6H), 1.63-1.66 (m, 2H), 1.89-2.18 (m, 11H), 2.74 (s, 3H), 3.18-3.27 (m, 1H), 3.71 (s, 3H), 4.20-4.25 (m, 1H), 6.00 (bs, 1H), 6.41 (bs, 1H), 6.93-6.95 (m, 1H) 
     Example 27 
     5-[[(1-Acetylpiperidin-4-yl)methyl] (methyl)amino]-N-[(E)-5-hydroxy-2-adamantyl]-1-methyl-1H-pyrazole-3-carboxamide 
     
       
         
         
             
             
         
       
       
         
         
             
             
         
       
     
     Step (i): 
     Compound I (6.2 g) was dissolved in dichloromethane (70 mL), and then thereto were added 2M methylamine-THF solution (40 mL) and acetic acid (2 mL), and the mixture was stirred at room temperature for 1 hour. Then, thereto was added NaBH(OAc) 3  (8.0 g) and the mixture was stirred at room temperature overnight. Then, thereto was added water, and then the mixture was concentrated in vacuo. Then, thereto was added saturated sodium bicarbonate water, and the mixture was extracted with chloroform. The organic layer was dried over sodium sulfate and concentrated in vacuo. The residue was purified by silica gel chromatography (eluent: chloroform/meththanol=10/1) to give Compound II (2.3 g). 
     Step (ii): 
     To a solution of 1,1′-thiocarbonyldiimidazole (1.1 g) in THF (25 mL) was added a solution of Compound II (2.3 g) in THF (5 mL), and the mixture was stirred at room temperature overnight. Then, thereto was added hydrazine monohydrate (1.7 mL), and the mixture was stirred at 70° C. for 6 hours and concentrated in vacuo. Then, thereto was added brine, and the mixture was extracted with chloroform. The organic layer was dried over sodium sulfate, and then concentrated in vacuo. The residue was purified by silica gel chromatography (eluent: chloroform/methanol=5/1) to give Compound III (2.5 g). 
     Step (iii): 
     Compound III (2.5 g) was dissolved in a mixed solvent of ethanol (25 mL) and THF (25 mL), and then thereto were added sodium bicarbonate (680 mg) and ethyl bromopyruvate (1.1 mL) and the mixture was stirred at 80° C. for 4 hours. Then, thereto was added acetic acid (25 mL), and the mixture was stirred at 70° C. for 3 hours and concentrated in vacuo. Then, thereto was added saturated sodium bicarbonate water, and the mixture was extracted with ethyl acetate. The organic layer was dried over sodium sulfate and concentrated in vacuo. The residue was purified by silica gel chromatography (eluent: hexane/ethyl acetate=1/1) to give Compound IV (1.3 g). 
     Step (iv): 
     To a solution of sodium hydride (160 mg) in THF (10 mL) was added dropwise a solution of Compound IV (1.3 g) in THF (6 mL) at 0° C., and the mixture was stirred at room temperature for 1 hour. Then, thereto was slowly added methyl iodide (310 μL) at 0° C., and the mixture was stirred at room temperature overnight. Then, thereto was added water, and the mixture was extracted with ethyl acetate. The organic layer was dried over sodium sulfate and concentrated in vacuo. The residue was purified by silica gel chromatography (eluent: hexane/ethyl acetate=2/1) to give Compound V (851 mg). 
     Step (v): 
     Compound V (845 mg) was dissolved in ethanol (7 mL), and then thereto was added 6N lithium hydroxide solution (1 mL) and the mixture was stirred at 40° C. for 3 hours. The reaction solution was concentrated in vacuo, and then acidified by 1N hydrochloric acid and extracted with chloroform. The organic layer was dried over sodium sulfate and concentrated in vacuo to give Compound VI (750 mg). 
     Step (vi): 
     Compound VI (390 mg) was dissolved in DMF (5 mL), and then thereto were added (E)-4-aminoadamantan-1-ol hydrochloride (305 mg), WSCI.HCl (382 mg), HOBt.H 2 O (270 mg) and triethylamine (340 μL), and the mixture was stirred at room temperature overnight. Then, thereto was added saturated sodium bicarbonate water, and then the mixture was extracted with ethyl acetate and the organic layer was washed with brine. The organic layer was dried over sodium sulfate and concentrated in vacuo. The residue was purified by preparative TLC (eluent: chloroform/methanol=10/1) to give Compound VII (450 mg). 
     Step (vii): 
     Compound VII (450 mg) was dissolved in methanol (4 mL), and then thereto was added palladium-carbon (50 mg) and the mixture was stirred under hydrogen atmosphere (3 atm) for 4.5 hours. The resulting solid was filtered through Celite®, and then the filtrate was concentrated to give Compound VIII (340 mg). 
     Step (viii): 
     Compound VIII (80 mg) was dissolved in dichloromethane (1 mL), and then thereto were added triethylamine (86 μL) and acetyl chloride (30 μL) and the mixture was stirred at room temperature for 3 hours. Then, thereto was added 2N sodium hydroxide solution, and the mixture was extracted with chloroform. The organic layer was dried over sodium sulfate and concentrated in vacuo. The residue was purified by preparative TLC (eluent: chloroform/meththanol=10/1) to give the titled Compound IX (38 mg). 
       1 H-NMR (CDCl 3 ) δ 1.05-1.18 (m, 2H), 1.45-1.96 (m, 14H), 2.07 (s, 3H), 2.16-2.21 (m, 3H), 2.42-2.52 (m, 1H), 2.63 (s, 3H), 2.68-2.78 (m, 2H), 2.92-3.05 (m, 1H), 3.72 (s, 3H), 3.73-3.83 (m, 1H), 4.10-4.19 (m, 1H), 4.55-4.65 (m, 1H), 6.38 (s, 1H), 7.08-7.14 (m, 1H) 
     Example 28 
     5-[[(1-Acetylpiperidin-4-yl)methyl] (methyl)amino]-4-chloro-N-[(2s,5r)-5-hydroxy-2-adamantyl]-1-methyl-1H-pyrazole-3-carboxamide 
     
       
         
         
             
             
         
       
     
     Step (ix): 
     Compound (16 mg) of Example 27 was dissolved in DMF (200 μL), and then thereto was added N-chlorosuccinimide (6 mg) and the mixture was stirred at 65° C. for 3 hours. Then, thereto was added water, and then the mixture was extracted with ethyl acetate. The organic layer was washed with brine, dried over sodium sulfate and concentrated in vacuo. The residue was purified by preparative TLC (eluent: chloroform/methanol=10/1) to give the titled Compound X (7 mg) as a white solid. 
       1 H-NMR (CDCl 3 ) δ 1.05-1.18 (m, 2H), 1.44-1.60 (m, 3H), 1.72-1.97 (m, 9H), 2.08 (s, 3H), 2.15-2.26 (m, 3H), 2.45-2.56 (m, 1H), 2.72-2.85 (m, 5H), 2.91-3.12 (m, 3H), 3.73 (s, 3H), 3.75-3.85 (m, 1H), 4.15-4.25 (m, 1H), 4.55-4.68 (m, 1H), 6.96-7.08 (m, 1H), 
     Example 29 
     4-Chloro-5-[cyclobutyl(2,2,2-trifluoroethyl)amino]-N-[(E)-5-hydroxy-2-adamantyl]-1-methyl-1H-pyrazole-3-carboxamide 
     
       
         
         
             
             
         
       
     
     Compound (100 mg) of Reference Example 7 was dissolved in DMF (1.5 mL), and then thereto were added (E)-4-aminoadamantan-1-ol hydrochloride (78 mg), WSCI.HCl (122 mg), HOBt.H 2 O (86 mg) and triethylamine (150 μL), and the mixture was stirred at room temperature overnight. Then, thereto was added water, and then the mixture was extracted with ethyl acetate. The organic layer was washed with brine. The organic layer was dried over sodium sulfate and concentrated in vacuo. The residue was purified by preparative TLC (eluent: chloroform/methanol=10/1) to give the titled Compound (128 mg) as a white solid. 
       1 H-NMR (CDCl 3 ) δ 1.42-1.68 (m, 5H), 1.71-2.00 (m, 10H), 2.02-2.29 (m, 5H), 3.45-3.80 (m, 5H), 3.80-3.95 (m, 1H), 4.16-4.25 (m, 1H), 6.99-7.09 (m, 1H) 
     Compounds of Examples 30-131 were prepared in the similar manner. 
     
       
         
           
               
            
               
                   
               
               
                 [Chemical Formula 73] 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
               
            
           
           
               
               
               
               
               
               
            
               
                   
                 Example No. 
                 R A   
                 R B   
                 R C   
                 R D   
               
               
                   
                   
               
               
                   
                 30 
                 CH 3   
                 CH 2 CH 3   
                 CH 3   
                 Cl 
               
               
                   
                   
               
               
                   
                 31 
                 CH 3   
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 CH 3   
                 Cl 
               
               
                   
                   
               
               
                   
                 32 
                 CH 3   
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 CH 3   
                 Cl 
               
               
                   
                   
               
               
                   
                 33 
                 CH 3   
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 CH 2 CH 3   
                 H 
               
               
                   
                   
               
               
                   
                 34 
                 CH 3   
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 CH 2 CH 3   
                 Cl 
               
               
                   
                   
               
               
                   
                 35 
                 CH 3   
                 CH 3   
                 CH 2 CH 3   
                 Cl 
               
               
                   
                   
               
               
                   
                 36 
                 CH 2 CH 3   
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 CH 3   
                 Cl 
               
               
                   
                   
               
               
                   
                 37 
                 CH 2 CH 3   
                 CH 2 CH 3   
                 CH 3   
                 Cl 
               
               
                   
                   
               
               
                   
                 38 
                 CH 2 CH 3   
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 CH 3   
                 H 
               
               
                   
                   
               
               
                   
                 39 
                 CH 3   
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 CH 3   
                 Cl 
               
               
                   
                   
               
               
                   
                 40 
                 CH 3   
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 CH 3   
                 Cl 
               
               
                   
                   
               
               
                   
                 41 
                 CH 3   
                 CH 2 —CF 3   
                 CH 3   
                 Cl 
               
               
                   
                 42 
                 CH 3   
                 CH 2 —CF 3   
                 CH 3   
                 H 
               
               
                   
                   
               
               
                   
                 43 
                 CH 3   
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 CH 3   
                 H 
               
               
                   
                   
               
            
           
         
       
     
     Example 30 
       1 H-NMR (CDCl 3 ) δ 1.02 (t, J=8.0 Hz, 3H), 1.61-1.63 (m, 4H), 1.88-1.90 (m, 2H), 1.97-2.04 (m, 4H), 2.12-2.16 (m, 2H), 2.30 (m, 1H), 2.80 (s, 3H), 3.10 (q, J=8.0 Hz, 2H), 3.70 (s, 3H), 4.18 (m, 1H), 5.21 (bs, 1H), 5.59 (bs, 1H), 7.08 (m, 1H) 
     Example 31 
       1 H-NMR (CDCl 3 ) δ 1.08 (d, J=4.0 Hz, 6H), 1.86-1.88 (m, 4H), 1.97-2.04 (m, 6H), 2.15-2.17 (m, 3H), 2.77 (s, 3H), 3.38 (m, 1H), 3.70 (s, 3H), 4.20 (m, 1H), 5.25 (bs, 1H), 5.60 (bs, 1H), 7.10 (m, 1H) 
     Example 32 
       1 H-NMR (CDCl 3 ) δ 0.89 (t, J=8.0 Hz, 3H), 1.39 (q, J=8.0 Hz, 2H), 1.61-1.65 (m, 2H), 1.89-1.92 (m, 3H), 1.97-2.06 (m, 4H), 2.15-2.17 (m, 2H), 2.80 (s, 3H), 3.06 (t, J=8.0 Hz, 3H), 3.72 (s, 3H), 4.02 (m, 1H), 4.22 (m, 1H), 5.34 (bs, 1H), 5.66 (bs, 1H), 7.08 (m, 1H) 
     Example 33 
       1 H-NMR (CDCl 3 ) δ 1.10 (d, J=8.0 Hz, 6H), 1.40-1.47 (m, 3H), 1.60-1.67 (m, 2H), 1.88-1.95 (m, 2H), 1.98-2.12 (m, 6H), 2.17-2.23 (m, 2H), 2.60 (s, 3H), 3.13-3.18 (m, 2H), 4.07-4.14 (m, 2H), 4.21 (m, 1H), 5.35 (bs, 1H), 5.64 (bs, 1H), 6.45 (s, 1H), 7.34 (m, 1H) 
     Example 34 
       1 H-NMR (CDCl 3 ) δ 1.10 (d, J=8.0 Hz, 6H), 1.38-1.43 (m, 3H), 1.62-1.69 (m, 2H), 1.89-1.96 (m, 4H), 2.00-2.13 (m, 5H), 2.16-2.23 (m, 2H), 2.79 (s, 3H), 3.39 (m, 1H), 4.11-4.15 (m, 2H), 4.24 (m, 1H), 6.01 (bs, 1H), 6.50 (bs, 1H), 7.18 (m, 1H) 
     Example 35 
       1 H-NMR (CDCl 3 ) δ 1.40 (t, J=8.0 Hz, 3H), 1.59-1.68 (m, 2H), 1.89-1.93 (m, 4H), 1.99-2.06 (m, 5H), 2.19-2.23 (m, 2H), 2.84 (s, 6H), 4.09 (q, J=8.0 Hz, 2H), 4.20 (m, 1H), 5.21 (bs, 1H), 5.60 (bs, 1H), 7.10 (m, 1H) 
     Example 36 
       1 H-NMR (CDCl 3 ) δ 0.90-0.93 (m, 3H), 1.08-1.09 (m, 6H), 1.62-1.65 (m, 2H), 1.92-1.94 (m, 4H), 1.99-2.07 (m, 5H), 2.19 (bs, 2H), 3.17-3.19 (m, 2H), 3.39-3.45 (m, 1H), 3.72 (s, 3H), 4.21-4.23 (m, 1H), 5.44 (bs, 1H), 5.65 (bs, 1H), 7.12-7.14 (m, 1H) 
     Example 37 
       1 H-NMR (CDCl 3 ) δ 0.98-1.01 (m, 6H), 1.60-1.66 (m, 2H), 1.91-1.93 (m, 4H), 1.99-2.09 (m, 5H), 2.19 (bs, 2H), 3.13-3.19 (m, 4H), 3.74 (s, 3H), 4.21-4.23 (m, 1H), 5.34 (bs, 1H), 5.70 (bs, 1H), 7.11-7.13 (m, 1H) 
     Example 38 
       1 H-NMR (CDCl 3 ) δ 0.88-0.92 (m, 4H), 1.04-1.05 (m, 6H), 1.61-1.65 (m, 2H), 1.93-2.08 (m, 9H), 2.18 (bs, 1H), 2.88-2.94 (m, 2H), 3.11-3.18 (m, 1H), 3.73 (s, 3H), 4.20-4.22 (m, 1H), 5.33 (bs, 1H), 5.61 (bs, 1H), 6.49 (s, 1H), 7.21-7.23 (m, 1H) 
     Example 39 
       1 H-NMR (CDCl 3 ) δ 1.59-1.66 (m, 2H), 1.85-2.09 (m, 9H), 2.15-2.24 (m, 2H), 2.88 (s, 3H), 3.26-3.33 (m, 5H), 3.35-3.41 (m, 2H), 3.75 (s, 3H), 4.15-4.24 (m, 1H), 5.62 (bs, 1H), 5.78 (bs, 1H), 7.06-7.14 (m, 1H) 
     Example 40 
       1 H-NMR (CDCl 3 ) δ 0.89-0.93 (m, 6H), 1.59-1.78 (m, 3H), 1.85-2.09 (m, 9H), 2.15-2.21 (m, 2H), 2.77 (s, 3H), 2.88-2.93 (m, 2H), 3.74 (s, 3H), 4.17-4.25 (m, 1H), 5.45 (bs, 1H), 5.71 (bs, 1H), 7.07-7.14 (m, 1H) 
     Example 41 
       1 H-NMR (CDCl 3 ) δ 1.58-1.70 (m, 2H), 1.86-2.10 (m, 9H), 2.15-2.22 (m, 2H), 2.95 (s, 3H), 3.59-3.71 (m, 2H), 3.78 (s, 3H), 4.18-4.25 (m, 1H), 5.58 (bs, 1H), 5.73 (bs, 1H), 7.07-7.13 (m, 1H) 
     Example 42 
       1 H-NMR (CDCl 3 ) δ 1.58-1.70 (m, 2H), 1.88-2.12 (m, 9H), 2.14-2.21 (m, 2H), 2.86 (s, 3H), 3.42-3.51 (m, 2H), 3.78 (s, 3H), 4.15-4.23 (m, 1H), 5.34 (bs, 1H), 5.63 (bs, 1H), 6.48 (s, 1H), 7.13-7.23 (m, 1H) 
     Example 43 
       1 H-NMR (CDCl 3 ) δ 0.95-1.04 (m, 3H), 1.58-1.69 (m, 2H), 1.88-2.12 (m, 9H), 2.13-2.22 (m, 2H), 2.95-3.04 (m, 2H), 3.05-3.13 (m, 2H), 3.30 (s, 3H), 3.32-3.40 (m, 2H), 3.75 (s, 3H), 4.17-4.24 (m, 1H), 5.38 (bs, 1H), 5.65 (bs, 1H), 6.47 (s, 1H), 7.15-7.24 (m, 1H) 
     
       
         
           
               
            
               
                   
               
               
                 [Chemical Formula74] 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
               
            
           
           
               
               
               
               
               
            
               
                 Example 
                   
                   
                   
                   
               
               
                 No. 
                 R A   
                 R B   
                 R C   
                 R D   
               
               
                   
               
               
                 44 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 CH 3   
                 H 
               
               
                   
               
               
                 45 
                 CH 2 CH 3   
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 CH 3   
                 Cl 
               
               
                   
               
               
                 46 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 CH 3   
                 Cl 
               
               
                   
               
               
                 47 
                 CH 3   
                 CH 2 —CF 3   
                 CH 2 CH 3   
                 H 
               
               
                 48 
                 CH 3   
                 CH 2 —CF 3   
                 CH 3   
                 CH 3   
               
               
                 49 
                 CH 3   
                 CH 2 —CF 3   
                 CH 2 CH 3   
                 Cl 
               
               
                   
               
               
                 50 
                 CH 2 —CF 3   
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 CH 3   
                 Cl 
               
               
                   
               
               
                 51 
                 CH 2 —CF 3   
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 CH 3   
                 Cl 
               
               
                   
               
               
                 52 
                 CH 2 —CF 3   
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 CH 3   
                 H 
               
               
                   
               
               
                 53 
                 CH 2 —CF 3   
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 CH 3   
                 H 
               
               
                   
               
               
                 54 
                 CH 3   
                 CH 2 —CF 3   
                 CH 2 CH 3   
                 Cl 
               
               
                   
               
               
                 55 
                 CH 2 —CF 3   
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 CH 3   
                 H 
               
               
                   
               
               
                 56 
                 CH 2 —CF 3   
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 CH 3   
                 Cl 
               
               
                   
               
            
           
         
       
     
     Example 44 
       1 H-NMR (CDCl 3 ) δ 1.00-1.12 (m, 6H), 1.58-1.69 (m, 2H), 1.89-2.12 (m, 9H), 2.13-2.23 (m, 2H), 3.02-3.12 (m, 2H), 3.13-3.31 (m, 6H), 3.75 (s, 3H), 4.18-4.25 (m, 1H), 5.35 (bs, 1H), 5.64 (bs, 1H), 6.52 (s, 1H), 7.18-7.27 (m, 1H) 
     Example 45 
       1 H-NMR (CDCl 3 ) δ 0.95-1.04 (m, 3H), 1.58-1.69 (m, 2H), 1.85-2.10 (m, 9H), 2.15-2.22 (m, 2H), 3.15-3.22 (m, 2H), 3.28-3.37 (m, 7H), 3.75 (s, 3H), 4.18-4.25 (m, 1H), 5.30 (bs, 1H), 5.64 (bs, 1H), 7.15-7.27 (m, 1H) 
     Example 46 
       1 H-NMR (CDCl 3 ) δ 1.05-1.16 (m, 6H), 1.58-1.68 (m, 2H), 1.88-2.10 (m, 9H), 2.18-2.24 (m, 2H), 3.22-3.28 (m, 5H), 3.29-3.48 (m, 3H), 3.75 (s, 3H), 4.18-4.25 (m, 1H), 5.32 (bs, 1H), 5.65 (bs, 1H), 7.05-7.16 (m, 1H) 
     Example 47 
       1 H-NMR (CDCl 3 ) δ 1.38-1.48 (m, 3H), 1.59-1.70 (m, 2H), 1.88-2.11 (m, 9H), 2.14-2.21 (m, 2H), 2.84 (s, 3H), 3.40-3.52 (m, 2H), 4.07-4.24 (m, 3H), 5.32 (bs, 1H), 5.63 (bs, 1H), 6.50 (s, 1H), 7.18-7.25 (m, 1H) 
     Example 48 
       1 H-NMR (CDCl 3 ) δ 1.56-1.75 (m, 2H), 1.89-2.10 (m, 9H), 2.13-2.19 (m, 2H), 2.28 (s, 3H), 2.92 (s, 3H), 3.50-3.62 (m, 2H), 3.74 (s, 3H), 4.14-4.22 (m, 1H), 5.32 (bs, 1H), 5.62 (bs, 1H), 7.18-7.29 (m, 1H) 
     Example 49 
       1 H-NMR (CDCl 3 ) δ 1.38-1.50 (m, 3H), 1.58-1.72 (m, 2H), 1.86-2.11 (m, 9H), 2.15-2.25 (m, 2H), 2.95 (s, 3H), 3.60-3.72 (m, 2H), 4.08-4.26 (m, 3H), 5.33 (bs, 1H), 5.64 (bs, 1H), 7.05-7.14 (m, 1H) 
     Example 50 
       1 H-NMR (CDCl 3 ) δ 1.62-1.69 (m, 2H), 1.88-2.11 (m, 9H), 2.15-2.24 (m, 2H), 3.27-3.45 (m, 7H), 3.72-3.87 (m, 5H), 4.16-4.27 (m, 1H), 5.32 (bs, 1H), 5.64 (bs, 1H), 7.06-7.14 (m, 1H) 
     Example 51 
       1 H-NMR (CDCl 3 ) δ 1.58-1.72 (m, 4H), 1.85-2.12 (m, 9H), 2.13-2.22 (m, 2H), 3.23-3.36 (m, 5H), 3.36-3.46 (m, 2H), 3.63-3.72 (m, 2H), 3.77 (s, 3H), 4.16-4.25 (m, 1H), 5.29 (bs, 1H), 5.62 (bs, 1H), 7.05-7.14 (m, 1H) 
     Example 52 
       1 H-NMR (CDCl 3 ) δ 1.59-1.70 (m, 2H), 1.88-2.11 (m, 9H), 2.14-2.21 (m, 2H), 3.18-3.25 (m, 2H), 3.32 (s, 3H), 3.36-3.43 (m, 2H), 3.61-3.72 (m, 2H), 3.77 (s, 3H), 4.17-4.23 (m, 1H), 5.33 (bs, 1H), 5.63 (bs, 1H), 6.55 (s, 1H), 7.16-7.25 (m, 1H) 
     Example 53 
       1 H-NMR (CDCl 3 ) δ 1.59-1.72 (m, 4H), 1.89-2.11 (m, 9H), 2.12-2.22 (m, 2H), 3.09-3.11 (m, 2H), 3.30 (s, 3H), 3.33-3.41 (m, 2H), 3.45-3.66 (m, 2H), 3.77 (s, 3H), 4.16-4.25 (m, 1H), 5.35 (bs, 1H), 5.63 (bs, 1H), 6.54 (s, 1H), 7.16-7.23 (m, 1H) 
     Example 54 
       1 H-NMR (CDCl 3 ) δ 1.39-1.46 (m, 3H), 1.59-1.68 (m, 2H), 1.85-2.20 (m, 12H), 2.95 (s, 3H), 3.61-3.71 (m, 2H), 4.08-4.17 (m, 2H), 4.18-4.25 (m, 1H), 7.08-7.14 (m, 1H) 
     Example 55 
       1 H-NMR (CDCl 3 ) δ 1.05-1.14 (m, 6H), 1.61-1.68 (m, 2H), 1.90-2.10 (m, 9H), 2.15-2.21 (m, 2H), 3.18-3.28 (m, 1H), 3.41-3.52 (m, 2H), 3.77 (s, 3H), 4.17-4.24 (m, 1H), 5.31 (bs, 1H), 5.62 (bs, 1H), 6.54 (s, 1H), 7.15-7.27 (m, 1H) 
     Example 56 
       1 H-NMR (CDCl 3 ) δ 1.08-1.21 (m, 6H), 1.60-1.68 (m, 2H), 1.89-2.10 (m, 9H), 2.18-2.22 (m, 2H), 3.38-3.48 (m, 1H), 3.50-3.82 (m, 5H), 4.18-4.24 (m, 1H), 5.30 (bs, 1H), 5.63 (bs, 1H), 7.08-7.17 (m, 1H) 
     
       
         
           
               
               
            
               
                   
               
               
                   
                 [Chemical Formula 75] 
               
               
                   
               
            
           
           
               
            
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
               
               
                   
               
            
           
           
               
               
               
               
               
            
               
                 Ex-  
                   
                   
                   
                   
               
               
                 am- 
                   
                   
                   
                   
               
               
                 ple 
                   
                   
                   
                   
               
               
                 No. 
                 R B   
                 R D   
                 R 1   
                 R 2   
               
               
                   
               
               
                 57 
                 CH 3   
                 Cl 
                 H 
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
               
               
                 58 
                 CH 3   
                 Cl 
                 H 
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
               
               
                 59 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Cl 
                 H 
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
               
               
                 60 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Cl 
                 H 
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
               
               
                 61 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Cl 
                 H 
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
               
               
                 62 
                 CH 2 —CF 3   
                 CH 3   
                 CH 2 CH 3   
                 CH 2 CH 3   
               
               
                   
               
            
           
         
       
     
     Example 57 
       1 H-NMR (CDCl 3 ) δ 1.62-1.65 (m, 2H), 1.75 (m, 1H), 1.89-1.95 (m, 4H), 2.05-2.10 (m, 4H), 2.15-2.28 (m, 2H), 2.84 (s, 6H), 3.71 (s, 3H), 4.21 (m, 1H), 4.45 (d, J=4.0 Hz, 2H), 6.24 (m, 1H), 7.07 (m, 1H), 7.14 (d, J=8.0 Hz, 2H), 8.53 (d, J=8.0 Hz, 2H) 
     Example 58 
       1 H-NMR (CDCl 3 ) δ 1.60-1.63 (m, 2H), 1.80-1.87 (m, 5H), 2.01-2.05 (m, 4H), 2.13-2.15 (m, 2H), 2.84 (s, 6H), 3.71 (s, 3H), 4.18 (m, 1H), 4.45 (d, J=4.0 Hz, 2H), 6.21 (m, 1H), 7.07 (d, J=8.0 Hz, 1H), 7.25 (d, J=8.0 Hz, 1H), 7.59 (d, J=8.0 Hz, 1H), 8.49-8.51 (m, 2H) 
     Example 59 
       1 H-NMR (CDCl 3 ) δ 0.90 (t, J=8.0 Hz, 3H), 1.46 (q, J=8.0 Hz, 2H), 1.62-1.65 (m, 2H), 1.88-1.91 (m, 5H), 2.01-2.07 (m, 5H), 2.15-2.17 (m, 2H), 2.81 (s, 3H), 3.04 (t, J=8.0 Hz, 2H), 3.46-3.50 (m, 2H), 3.73 (s, 3H), 3.76-3.80 (m, 2H), 4.20 (m, 1H), 6.34 (m, 1H), 7.17 (m, 1H) 
     Example 60 
       1 H-NMR (CDCl 3 ) δ 0.90 (t, J=8.0 Hz, 3H), 1.44 (q, J=8.0 Hz, 2H), 1.62-1.65 (m, 2H), 1.86-1.93 (m, 4H), 1.98-2.08 (m, 4H), 2.15-2.20 (m, 3H), 2.81 (s, 3H), 3.04 (t, J=8.0 Hz, 2H), 3.37 (s, 3H), 3.42-3.50 (m, 4H), 3.72 (s, 3H), 4.21 (m, 1H), 6.12 (m, 1H), 7.15 (m, 1H) 
     Example 61 
       1 H-NMR (CDCl 3 ) δ 1.10 (d, J=4.0 Hz, 6H), 1.60-1.63 (m, 2H), 1.86-1.95 (m, 8H), 2.05 (m, 1H), 2.13-2.16 (m, 2H), 2.79 (s, 3H), 3.28-3.31 (m, 2H), 3.38 (m, 1H), 3.68-3.72 (m, 5H), 4.18 (m, 1H), 6.51 (m, 1H), 7.10 (m, 1H), 7.57-7.62 (m, 2H), 7.70 (m, 1H), 7.90-7.92 (m, 2H) 
     Example 62 
       1 H-NMR (CDCl 3 ) δ 1.08-1.17 (m, 6H), 1.58-1.70 (m, 2H), 1.86-1.95 (m, 2H), 2.01-2.25 (m, 9H), 2.28 (s, 3H), 2.92 (s, 3H), 3.36-3.50 (m, 4H), 3.52-3.61 (m, 2H), 3.74 (s, 3H), 4.18-4.25 (m, 1H), 7.22-7.29 (m, 1H) 
     
       
         
           
               
               
            
               
                   
               
               
                   
                 [Chemical Formula 76] 
               
               
                   
               
            
           
           
               
            
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
               
            
           
           
               
               
               
               
               
            
               
                 Ex-  
                   
                   
                   
                   
               
               
                 am- 
                   
                   
                   
                   
               
               
                 ple 
                   
                   
                   
                   
               
               
                 No. 
                 R A   
                 R B   
                 R D   
                 A 
               
               
                   
               
               
                 63 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 CH 3   
                 H 
                 CONH 2   
               
               
                   
               
               
                 64 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 CH 3   
                 Cl 
                 OH 
               
               
                   
               
               
                 65 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 CH 3   
                 Cl 
                 CONH 2   
               
               
                   
               
               
                 66 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 CH 3   
                 Cl 
                 CONH 2   
               
               
                   
               
               
                 67 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 CH2—CF3 
                 Cl 
                 OH 
               
               
                   
               
               
                 68 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 H 
                 CONH 2   
               
               
                   
               
               
                 69 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 H 
                 CONH 2   
               
               
                   
               
               
                 70 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Cl 
                 OH 
               
               
                   
               
               
                 71 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Cl 
                 OH 
               
               
                   
               
            
           
         
       
     
     Example 63 
       1 H-NMR (CDCl 3 ) δ 1.62-1.66 (m, 2H), 1.93-2.08 (m, 9H), 2.15-2.18 (m, 2H), 2.61 (s, 3H), 2.87-2.92 (m, 2H), 3.07-3.12 (m, 2H), 3.75 (s, 3H), 3.90 (m, 1H), 4.22 (m, 1H), 5.17 (bs, 1H), 5.58 (bs, 1H), 6.51 (s, 1H), 7.13-7.19 (m, 5H) 
     Example 64 
       1 H-NMR (CDCl 3 ) δ 1.53-1.62 (m, 4H), 1.78-1.95 (m, 7H), 2.17-2.23 (m, 3H), 2.77-2.79 (m, 2H), 2.84 (s, 3H), 3.06-3.12 (m, 2H), 3.64 (s, 3H), 4.19 (m, 1H), 4.30 (m, 1H), 7.04 (m, 1H), 7.15-7.20 (m, 4H) 
     Example 65 
       1 H-NMR (CDCl 3 ) δ 1.63-1.69 (m, 2H), 1.89-1.95 (m, 4H), 2.02-2.07 (m, 5H), 2.15-2.19 (m, 2H), 2.77-2.82 (m, 2H), 2.84 (s, 3H), 3.06-3.11 (m, 2H), 3.64 (s, 3H), 4.23 (m, 1H), 4.32 (m, 1H), 5.36 (bs, 1H), 5.66 (bs, 1H), 7.11-7.15 (m, 5H) 
     Example 66 
       1 H-NMR (CDCl 3 ) δ 0.05-0.10 (m, 2H), 0.39-0.48 (m, 2H), 0.79-0.90 (m, 1H), 1.58-1.68 (m, 2H), 1.88-2.09 (m, 9H), 2.16-2.23 (m, 2H), 2.86 (s, 3H), 2.86-2.93 (m, 2H), 3.75 (s, 3H), 4.17-4.23 (m, 1H), 5.46 (bs, 1H), 5.71 (bs, 1H), 7.07-7.14 (m, 1H) 
     Example 67 
       1 H-NMR (CDCl 3 ) δ 0.52-0.68 (m, 4H), 1.42-1.49 (m, 1H), 1.51-1.60 (m, 2H), 1.73-1.98 (m, 8H), 2.15-2.27 (m, 3H), 3.00-3.08 (m, 1H), 3.68-3.82 (m, 5H), 4.16-4.25 (m, 1H), 7.00-7.08 (m, 1H) 
     Example 68 
       1 H-NMR (CDCl 3 ) δ 0.44-0.45 (m, 2H), 0.63-0.64 (m, 2H), 1.61-1.66 (m, 2H), 1.75-1.82 (m, 2H), 1.89-2.18 (m, 11H), 2.49-2.54 (m, 1H), 3.14-3.18 (m, 2H), 3.28 (s, 3H), 3.34-3.37 (m, 2H), 3.75-3.76 (m, 3H), 4.20-4.21 (m, 1H), 5.27-5.29 (m, 1H), 5.61-5.66 (m, 1H), 6.48 (s, 1H), 7.44-7.52 (m, 1H) 
     Example 69 
       1 H-NMR (CDCl 3 ) δ 0.45-0.46 (m, 2H), 0.60-0.63 (m, 2H), 1.61-1.64 (m, 2H), 1.89-2.07 (m, 8H), 2.18 (bs, 3H), 2.58-2.59 (m, 1H), 3.22-3.26 (m, 2H), 3.29 (s, 3H), 3.44-3.47 (m, 2H), 3.74 (s, 3H), 4.20-4.22 (m, 1H), 5.28 (bs, 1H), 5.63 (bs, 1H), 6.51 (s, 1H), 7.40-7.42 (m, 1H) 
     Example 70 
       1 H-NMR (CDCl 3 ) δ 0.38-0.41 (m, 2H), 0.54-0.58 (m, 2H), 1.68-1.82 (m, 10H), 1.91-1.94 (m, 2H), 2.14-2.23 (m, 4H), 2.90-2.95 (m, 1H), 3.23-3.27 (m, 2H), 3.30 (s, 3H), 3.36-3.39 (m, 2H), 3.65 (s, 3H), 4.19-4.21 (m, 1H), 7.03-7.05 (m, 1H) 
     Example 71 
       1 H-NMR (CDCl 3 ) δ 0.41-0.44 (m, 2H), 0.54-0.58 (m, 2H), 1.50-1.61 (m, 2H), 1.73-1.86 (m, 7H), 1.89-1.94 (m, 2H), 2.17-2.25 (m, 3H), 2.95-3.00 (m, 1H), 3.28 (s, 3H), 3.35-3.39 (m, 4H), 3.69 (s, 3H), 4.17-4.22 (m, 1H), 7.05-7.08 (m, 1H) 
     
       
         
           
               
            
               
                   
               
               
                 [Chemical Formula 77] 
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
               
            
           
           
               
               
               
               
               
            
               
                 Ex- 
                   
                   
                   
                   
               
               
                 ample 
                   
                   
                   
                   
               
               
                 No. 
                 R A   
                 R B   
                 R D   
                 A 
               
               
                   
               
               
                 72 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 H 
                 CONH 2   
               
               
                   
               
               
                 73 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Cl 
                 OH 
               
               
                   
               
               
                 74 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Cl 
                 CONH 2   
               
               
                   
               
               
                 75 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 H 
                 CONH 2   
               
               
                   
               
               
                 76 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Cl 
                 OH 
               
               
                   
               
               
                 77 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Cl 
                 CONH 2   
               
               
                   
               
               
                 78 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 H 
                 CONH 2   
               
               
                   
               
            
           
         
       
     
     Example 72 
       1 H-NMR (CDCl 3 ) δ 1.57-1.66 (m, 2H), 1.71-1.81 (m, 3H), 1.91-2.17 (m, 14H), 2.54-2.58 (m, 2H), 3.05-3.09 (m, 2H), 3.63-3.69 (m, 4H), 3.78 (s, 3H), 4.22-4.24 (m, 1H), 5.43 (bs, 1H), 5.67 (bs, 1H), 6.53 (s, 1H), 6.78-6.81 (m, 2H), 6.97-7.00 (m, 2H), 7.32-7.35 (m, 1H) 
     Example 73 
       1 H-NMR (CDCl 3 ) δ 0.39-0.43 (m, 2H), 0.55-0.59 (m, 2H), 1.52-1.56 (m, 2H), 1.78-1.94 (m, 9H), 2.19-2.23 (m, 3H), 2.71-2.75 (m, 2H), 2.92-2.96 (m, 1H), 3.43-3.48 (m, 5H), 3.78 (s, 3H), 4.19-4.21 (m, 1H), 6.65-6.66 (m, 1H), 6.70-6.75 (m, 2H), 7.04-7.06 (m, 1H), 7.16-7.20 (m, 1H) 
     Example 74 
       1 H-NMR (CDCl 3 ) δ 0.40-0.44 (m, 2H), 0.55-0.60 (m, 2H), 1.64-1.67 (m, 2H), 1.82-2.20 (m, 11H), 2.72-2.76 (m, 2H), 2.91-2.96 (m, 1H), 3.44-3.47 (m, 2H), 3.50 (s, 3H), 3.78 (s, 3H), 4.24-4.26 (m, 1H), 6.07 (bs, 1H), 6.55 (bs, 1H), 6.66-6.68 (m, 1H), 6.71-6.75 (m, 2H), 7.14-7.23 (m, 2H) 
     Example 75 
       1 H-NMR (CDCl 3 ) δ 0.42-0.46 (m, 2H), 0.56-0.63 (m, 2H), 1.62-1.65 (m, 2H), 1.93-2.18 (m, 11H), 2.51-2.57 (m, 1H), 2.73-2.77 (m, 2H), 3.25-3.29 (m, 2H), 3.61 (s, 3H), 3.78 (s, 3H), 4.20-4.22 (m, 1H), 5.33 (bs, 1H), 5.65 (bs, 1H), 6.52 (s, 1H), 6.65-6.66 (m, 1H), 6.70-6.75 (m, 2H), 7.17-7.21 (m, 1H), 7.28-7.30 (m, 1H) 
     Example 76 
       1 H-NMR (CDCl 3 ) δ 0.39-0.42 (m, 2H), 0.54-0.59 (m, 2H), 1.52-1.56 (m, 2H), 1.74-1.95 (m, 9H), 2.19-2.24 (m, 3H), 2.67-2.71 (m, 2H), 2.91-2.96 (m, 1H), 3.40-3.44 (m, 2H), 3.48 (s, 3H), 3.78 (s, 3H), 4.19-4.21 (m, 1H), 6.79-6.86 (m, 2H), 7.02-7.06 (m, 3H) 
     Example 77 
       1 H-NMR (CDCl 3 ) δ 0.39-0.43 (m, 2H), 0.55-0.59 (m, 2H), 1.64-1.67 (m, 2H), 1.89-2.20 (m, 11H), 2.67-2.71 (m, 2H), 2.90-2.95 (m, 1H), 3.40-3.44 (m, 2H), 3.50 (s, 3H), 3.78 (s, 3H), 4.24-4.25 (m, 1H), 5.88 (bs, 1H), 6.34 (bs, 1H), 6.79-6.83 (m, 2H), 7.02-7.05 (m, 2H), 7.13-7.15 (m, 1H) 
     Example 78 
       1 H-NMR (CDCl 3 ) δ 0.42-0.45 (m, 2H), 0.59-0.62 (m, 2H), 1.62-1.65 (m, 2H), 1.93-2.19 (m, 11H), 2.51-2.55 (m, 1H), 2.67-2.74 (m, 2H), 3.23-3.27 (m, 2H), 3.62 (s, 3H), 3.78 (s, 3H), 4.21-4.23 (m, 1H), 5.30 (bs, 1H), 5.63 (bs, 1H), 6.50 (s, 1H), 6.79-6.83 (m, 2H), 7.01-7.05 (m, 2H), 7.33-7.35 (m, 1H) 
     
       
         
           
               
            
               
                   
               
               
                 [Chemical Formula 78] 
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
               
            
           
           
               
               
               
               
               
            
               
                   
                 Example No. 
                 R B   
                 R D   
                 A 
               
               
                   
               
               
                   
                 79 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Cl 
                 CONH 2   
               
               
                   
               
               
                   
                 80 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Cl 
                 OH 
               
               
                   
               
               
                   
                 81 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 H 
                 CONH 2   
               
               
                   
               
               
                   
                 82 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Cl 
                 OH 
               
               
                   
               
               
                   
                 83 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Cl 
                 CONH 2   
               
               
                   
               
               
                   
                 84 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 H 
                 OH 
               
               
                   
               
               
                   
                 85 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 H 
                 CONH 2   
               
               
                   
               
               
                   
                 86 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 H 
                 CONH 2   
               
               
                   
               
            
           
         
       
     
     Example 79 
       1 H-NMR (CDCl 3 ) δ 0.43-0.46 (m, 2H), 0.58-0.61 (m, 2H), 1.62-1.65 (m, 2H), 1.88-1.93 (m, 3H), 1.99-2.10 (m, 5H), 2.17-2.18 (m, 3H), 2.96-3.01 (m, 1H), 3.28 (s, 3H), 3.77 (s, 3H), 4.23 (m, 3H), 5.89 (bs, 1H), 6.35 (bs, 1H), 6.75-6.79 (m, 2H), 7.03-7.05 (m, 2H), 7.08-7.10 (m, 1H) 
     Example 80 
       1 H-NMR (CDCl 3 ) δ 0.43-0.46 (m, 2H), 0.56-0.61 (m, 2H), 1.51-1.54 (m, 2H), 1.72-1.83 (m, 7H), 1.91-1.94 (m, 2H), 2.17-2.22 (m, 3H), 2.97-3.02 (m, 1H), 3.26 (s, 3H), 3.76 (s, 3H), 4.17-4.19 (m, 1H), 4.23 (s, 2H), 6.74-6.78 (m, 2H), 6.99-7.01 (m, 1H), 7.02-7.06 (m, 2H) 
     Example 81 
       1 H-NMR (CDCl 3 ) δ 0.43-0.47 (m, 2H), 0.56-0.61 (m, 2H), 1.61-1.64 (m, 2H), 1.88-1.92 (m, 3H), 1.99-2.08 (m, 5H), 2.17-2.18 (m, 3H), 2.39-2.44 (m, 1H), 3.58 (s, 3H), 3.78 (s, 3H), 4.09 (s, 2H), 4.19-4.21 (m, 1H), 5.31 (bs, 1H), 5.64 (bs, 1H), 6.45 (s, 1H), 6.77-6.81 (m, 2H), 7.00-7.05 (m, 2H), 7.34-7.36 (m, 1H) 
     Example 82 
       1 H-NMR (CDCl 3 ) δ 0.47-0.51 (m, 2H), 0.60-0.65 (m, 2H), 1.52-1.56 (m, 3H), 1.73-1.83 (m, 6H), 1.91-1.94 (m, 2H), 2.18-2.22 (m, 3H), 2.97-3.02 (m, 1H), 3.04 (s, 3H), 3.35 (s, 3H), 4.16-4.18 (m, 1H), 4.40 (s, 2H), 6.99-7.00 (m, 1H), 7.38-7.39 (m, 2H), 7.84-7.86 (m, 2H) 
     Example 83 
       1 H-NMR (CDCl 3 ) δ 0.49-0.54 (m, 2H), 0.62-0.64 (m, 2H), 1.65-2.18 (m, 13H), 2.99-3.01 (m, 1H), 3.04 (s, 3H), 3.36 (s, 3H), 4.19-4.21 (m, 1H), 4.40 (s, 2H), 5.35 (bs, 1H), 5.69 (bs, 1H), 7.06-7.08 (m, 1H), 7.38-7.40 (m, 2H), 7.84-7.86 (m, 2H) 
     Example 84 
       1 H-NMR (CDCl 3 ) δ 0.46-0.50 (m, 2H), 0.58-0.62 (m, 2H), 1.52-1.55 (m, 2H), 1.78-1.94 (m, 9H), 2.19-2.21 (m, 3H), 2.42-2.45 (m, 1H), 3.05 (s, 3H), 3.58 (s, 3H), 4.15-4.17 (m, 1H), 4.21 (s, 2H), 6.45 (s, 1H), 7.09-7.11 (m, 1H), 7.34-7.36 (m, 2H), 7.84-7.86 (m, 2H) 
     Example 85 
       1 H-NMR (CDCl 3 ) δ 0.48-0.50 (m, 2H), 0.58-0.61 (m, 2H), 1.62-1.65 (m, 2H), 1.92-2.07 (m, 9H), 2.17 (bs, 2H), 2.43-2.46 (m, 1H), 3.05 (s, 3H), 3.59 (s, 3H), 4.18-4.20 (m, 1H), 4.22 (s, 2H), 5.66 (bs, 2H), 6.45 (s, 1H), 7.19-7.21 (m, 1H), 7.34-7.36 (m, 2H), 7.84-7.87 (m, 2H) 
     Example 86 
       1 H-NMR (CDCl 3 ) δ 0.40-0.44 (m, 2H), 0.56-0.61 (m, 2H), 1.62-1.65 (m, 2H), 1.93-2.18 (m, 11H), 2.48-2.53 (m, 1H), 2.71-2.75 (m, 2H), 3.21-3.26 (m, 2H), 3.58 (s, 3H), 4.20-4.22 (m, 1H), 5.44 (bs, 1H), 5.67 (bs, 1H), 6.51 (s, 1H), 7.03-7.05 (m, 2H), 7.22-7.24 (m, 3H) 
     
       
         
           
               
               
               
            
               
                   
               
               
                   
                   
                 [Chemical Formula 79] 
               
               
                   
               
            
           
           
               
            
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
               
            
           
           
               
               
               
               
            
               
                   
                 Example No. 
                 R B   
                 A 
               
               
                   
               
               
                   
                 87 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 CONH 2   
               
               
                   
               
               
                   
                 88 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 CONH 2   
               
               
                   
               
               
                   
                 89 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
               
               
                   
                 90 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
               
               
                   
                 91 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
               
               
                   
                 92 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
               
               
                   
                 93 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 CONH 2   
               
               
                   
               
               
                   
                 94 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 CONH 2   
               
               
                   
               
            
           
         
       
     
     Example 87 
       1 H-NMR (CDCl 3 ) δ 1.62-1.66 (m, 2H), 1.89-1.93 (m, 4H), 2.03-2.09 (m, 5H), 2.15-2.18 (m, 2H), 2.96 (s, 3H), 3.57-3.59 (m, 2H), 3.75 (s, 3H), 3.91 (s, 3H), 4.02-4.04 (m, 2H), 4.20 (m, 1H), 5.78 (bs, 1H), 6.20 (bs, 1H), 6.44 (s, 1H), 7.12 (m, 1H), 7.35 (s, 1H) 
     Example 88 
       1 H-NMR (CDCl 3 ) δ 1.62-1.66 (m, 2H), 1.89-1.93 (m, 4H), 2.03-2.10 (m, 5H), 2.17-2.19 (m, 2H), 2.93 (s, 3H), 3.47-3.50 (m, 2H), 3.73 (s, 3H), 3.76 (s, 3H), 3.91-3.93 (m, 2H), 4.21 (m, 1H), 5.94 (bs, 1H), 6.35 (bs, 1H), 6.76-6.83 (m, 4H), 7.13 (m, 1H) 
     Example 89 
       1 H-NMR (CDCl 3 ) δ 1.52-1.60 (m, 4H), 1.77-1.84 (m, 5H), 1.91-1.94 (m, 2H), 2.18-2.22 (m, 3H), 2.92 (s, 3H), 3.47-3.50 (m, 2H), 3.73 (s, 3H), 3.76 (s, 3H), 3.90-3.92 (m, 2H), 4.18 (m, 1H), 6.75-6.83 (m, 4H), 7.01 (m, 1H) 
     Example 90 
       1 H-NMR (CDCl 3 ) δ 1.51-1.54 (m, 2H), 1.77-1.84 (m, 6H), 1.90-1.93 (m, 2H), 2.17-2.22 (m, 4H), 2.92 (s, 3H), 3.52-3.55 (m, 2H), 3.76 (s, 3H), 4.01-4.04 (m, 2H), 4.18 (m, 1H), 6.87-6.92 (m, 2H), 7.02-7.09 (m, 3H) 
     Example 91 
       1 H-NMR (CDCl 3 ) δ 1.53-1.56 (m, 2H), 1.78-1.83 (m, 5H), 1.91-1.94 (m, 2H), 2.18-2.23 (m, 2H), 2.33-2.36 (m, 3H), 2.92 (s, 3H), 3.50-3.52 (m, 2H), 3.72 (s, 3H), 3.94-3.97 (m, 2H), 4.18 (m, 1H), 6.53-6.66 (m, 3H), 7.06 (m, 1H), 7.22 (m, 1H) 
     Example 92 
       1 H-NMR (CDCl 3 ) δ 1.52-1.55 (m, 2H), 1.77-1.84 (m, 7H), 1.91-1.94 (m, 2H), 2.18-2.22 (m, 3H), 2.92 (s, 3H), 3.48-3.51 (m, 2H), 3.72 (s, 3H), 3.91-3.95 (m, 2H), 4.39 (m, 1H), 6.75-6.78 (m, 2H), 6.93-6.98 (m, 3H) 
     Example 93 
       1 H-NMR (CDCl 3 ) δ 1.61-1.64 (m, 2H), 1.88-1.92 (m, 4H), 1.98-2.10 (m, 5H), 2.13-2.17 (m, 2H), 2.92 (s, 3H), 3.52-3.54 (m, 2H), 3.75 (s, 3H), 4.02-4.04 (m, 2H), 4.20 (m, 1H), 5.76 (bs, 1H), 6.12 (bs, 1H), 6.87-6.92 (m, 2H), 7.01-7.11 (m, 3H) 
     Example 94 
       1 H-NMR (CDCl 3 ) δ 1.62-1.66 (m, 2H), 1.85-1.93 (m, 4H), 2.02-2.10 (m, 5H), 2.15-2.18 (m, 2H), 2.93 (s, 3H), 3.47-3.51 (m, 2H), 3.78 (s, 3H), 3.92-3.98 (m, 2H), 4.21 (m, 1H), 5.87 (bs, 1H), 6.30 (bs, 1H), 6.75-6.78 (m, 2H), 6.93-6.98 (m, 2H), 7.12 (m, 1H). 
     
       
         
           
               
            
               
                   
               
               
                 [Chemical Formula 80] 
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
               
            
           
           
               
               
               
               
            
               
                 Example No. 
                 R B   
                 R D   
                 A 
               
               
                   
               
            
           
           
               
               
               
               
            
               
                 95 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 H 
                 CONH 2   
               
               
                   
               
               
                 96 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Cl 
                 OH 
               
               
                   
               
               
                 97 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Cl 
                 CONH 2   
               
               
                   
               
               
                 98 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Cl 
                 OH 
               
               
                   
               
               
                 99 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 H 
                 CONH 2   
               
               
                   
               
               
                 100 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 H 
                 CONH 2   
               
               
                   
               
               
                 101 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Cl 
                 CONH 2   
               
               
                   
               
            
           
         
       
     
     Example 95 
       1 H-NMR (CDCl 3 ) δ 1.61-1.64 (m, 2H), 1.92-2.07 (m, 9H), 2.15-2.18 (m, 2H), 2.79 (s, 3H), 3.30 (t, J=4.0 Hz, 2H), 3.77 (s, 3H), 4.01 (t, J=4.0 Hz, 2H), 4.20 (m, 1H), 5.53 (bs, 1H), 5.77 (bs, 1H), 6.44 (s, 1H), 6.76-6.79 (m, 2H), 7.21-7.24 (m, 2H), 7.28 (m, 1H) 
     Example 96 
       1 H-NMR (CDCl 3 ) δ 1.46-1.56 (m, 2H), 1.60-1.71 (m, 2H), 1.75-1.89 (m, 6H), 1.91-1.95 (m, 2H), 2.15-2.26 (m, 2H), 2.92 (s, 3H), 3.49-3.51 (t, J=4.0 Hz, 2H), 3.71 (s, 3H), 3.92-3.94 (t, J=4.0 Hz, 2H), 4.20 (m, 1H), 6.75 (d, J=8.0 Hz, 2H), 7.02 (m, 1H), 7.21 (d, J=8.0 Hz, 2H) 
     Example 97 
       1 H-NMR (CDCl 3 ) δ 1.62-1.65 (m, 2H), 1.89-1.99 (m, 4H), 2.02-2.07 (m, 5H), 2.15-2.18 (m, 2H), 2.92 (s, 3H), 3.47-3.52 (m, 2H), 3.71 (s, 3H), 3.92-3.95 (m, 2H), 4.20 (m, 1H), 5.57 (bs, 1H), 5.93 (bs, 1H), 6.74-6.76 (m, 2H), 7.09 (m, 1H), 7.20-7.23 (m, 2H) 
     Example 98 
       1 H-NMR (CDCl 3 ) δ 1.48-1.96 (m, 11H), 2.16-2.28 (m, 3H), 2.85 (s, 3H), 3.06 (s, 3H), 3.65 (s, 3H), 4.15-4.22 (m, 1H), 4.37 (s, 2H), 6.95-7.03 (m, 1H), 7.48-7.56 (m, 2H), 7.88-7.94 (m, 2H) 
     Example 99 
       1 H-NMR (CDCl 3 ) δ 1.21-1.29 (m, 3H), 1.59-1.68 (m, 2H), 1.90-2.11 (m, 9H), 2.16-2.22 (m, 2H), 2.49-2.58 (m, 2H), 2.60-2.68 (m, 2H), 2.70 (s, 3H), 3.05-3.14 (m, 2H), 3.77 (s, 3H), 4.15-4.24 (m, 1H), 5.34 (bs, 1H), 5.63 (bs, 1H), 6.39 (s, 1H), 7.15-7.23 (m, 1H) 
     Example 100 
       1 H-NMR (CDCl 3 ) δ 1.60-1.64 (m, 2H), 1.90-2.11 (m, 11H), 2.15-2.20 (m, 2H), 2.67 (s, 3H), 2.90 (s, 3H), 3.02-3.11 (m, 4H), 3.75 (s, 3H), 4.15-4.24 (m, 1H), 5.31 (bs, 1H), 5.62 (bs, 1H), 6.40 (s, 1H), 7.15-7.22 (m, 1H) 
     Example 101 
       1 H-NMR (CDCl 3 ) δ 1.58-1.68 (m, 2H), 1.85-2.11 (m, 11H), 2.15-2.22 (m, 2H), 2.83 (s, 3H), 2.91 (s, 3H), 3.02-3.11 (m, 2H), 3.26-3.35 (m, 2H), 3.75 (s, 3H), 4.16-4.25 (m, 1H), 5.27 (bs, 1H), 5.62 (bs, 1H), 7.05-7.14 (m, 1H) 
     Example 102 
     4-Chloro-5-[cyclopropyl(tetrahydro-2H-4-pyranyl)amino]-N-[(E)-5-hydroxy-2-adamantyl]-1-methyl-1H-pyrazole-3-carboxamide 
     
       
         
         
             
             
         
       
     
       1 H-NMR (CDCl 3 ) δ 0.12-0.19 (m, 1H), 0.43-0.54 (m, 2H), 0.67-0.74 (m, 1H), 1.25-1.45 (m, 2H), 1.52-1.69 (m, 4H), 1.73-1.94 (m, 8H), 2.09-2.28 (m, 4H), 2.83-2.89 (m, 1H), 3.31-3.46 (m, 3H), 3.64 (s, 3H), 3.91-4.02 (m, 2H), 4.18-4.21 (m, 1H), 7.03-7.04 (m, 1H) 
     
       
         
           
               
               
            
               
                   
               
               
                   
                 [Chemical Formula 82] 
               
               
                   
               
            
           
           
               
            
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
               
            
           
           
               
               
               
               
               
            
               
                 Example No. 
                 R A   
                 R B   
                 R C   
                 R D   
               
               
                   
               
               
                 103 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 CH 3   
                 Cl 
               
               
                   
               
               
                 104 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 CH 3   
                 Cl 
               
               
                   
               
               
                 105 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 CH 3   
                 H 
               
               
                   
               
               
                 106 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 CH 3   
                 Cl 
               
               
                   
               
               
                 107 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 CH 3   
                 F 
               
               
                   
               
               
                 108 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 CH 3   
                 Cl 
               
               
                   
               
               
                 109 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 CH 3   
                 Cl 
               
               
                   
               
               
                 110 
                 CH 3   
                 CH 2 CH 3   
                 CH 3   
                 F 
               
               
                 111 
                 CH 3   
                 CH 2 —CH 2 —CF 3   
                 CH 3   
                 Cl 
               
               
                 112 
                 CH 3   
                 CH 2 —CH 2 —CF 3   
                 CH 3   
                 F 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
            
               
                   
               
               
                   
                 [Chemical Formula 83] 
               
               
                   
               
            
           
           
               
            
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
               
            
           
           
               
               
               
               
               
            
               
                 Example No. 
                 R A   
                 R B   
                 R C   
                 R D   
               
               
                   
               
               
                 113 
                 CH 3   
                 CH 2 —CF 2 —CF 3   
                 CH 3   
                 F 
               
               
                   
               
               
                 114 
                 CH 3   
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 CH 3   
                 H 
               
               
                   
               
               
                 115 
                 CH 3   
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 CH 3   
                 F 
               
               
                   
               
               
                 116 
                 CH 3   
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 CH 3   
                 F 
               
               
                   
               
               
                 117 
                 CH 3   
                 CH 2 —CF 3   
                 CH 3   
                 F 
               
               
                   
               
               
                 118 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 CH 3   
                 F 
               
               
                   
               
               
                 119 
                 CH 3   
                 CH 2 —CH 2 —CH 3   
                 CH 3   
                 F 
               
               
                   
               
               
                 120 
                 CH 3   
                 CH 2 —CHF 2   
                 CH 3   
                 F 
               
               
                   
               
               
                 121 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 CH 3   
                 F 
               
               
                   
               
               
                 122 
                 CH 2 CH 3   
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 CH 3   
                 F 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
            
               
                   
               
               
                   
                   
                 [Chemical Formula 84] 
               
               
                   
               
            
           
           
               
               
            
               
                   
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
               
            
           
           
               
               
               
               
               
               
            
               
                   
                 Example No. 
                 R A   
                 R B   
                 R C   
                 R D   
               
               
                   
               
               
                   
                 123 
                 CH 3   
                 CH 2 —CHF 2   
                 CH 3   
                 Cl 
               
               
                   
               
               
                   
                 124 
                 CH 3   
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 CH 3   
                 F 
               
               
                   
               
            
           
         
       
     
     Example 103 
       1 H-NMR (CDCl 3 ) δ 0.36-0.39 (m, 2H), 0.52-0.56 (m, 2H), 1.60-1.63 (m, 2H), 1.66-1.73 (m, 2H), 1.88-2.16 (m, 11H), 2.87-2.92 (m, 1H), 3.21-3.25 (m, 2H), 3.28 (s, 3H), 3.35-3.38 (m, 2H), 3.64 (s, 3H), 4.18-4.20 (m, 1H), 5.94-6.02 (m, 2H), 7.09-7.11 (m, 1H) 
     Example 104 
       1 H-NMR (CDCl 3 ) δ 0.39-0.43 (m, 2H), 0.52-0.57 (m, 2H), 1.89-2.16 (m, 12H), 2.93-2.98 (m, 1H), 3.26 (s, 3H), 3.33-3.38 (m, 4H), 3.67 (s, 3H), 4.19-4.21 (m, 2H), 5.76-5.97 (m, 2H), 7.10-7.12 (m, 1H) 
     Example 105 
       1 H-NMR (CDCl 3 ) δ 0.42-0.46 (m, 4H), 0.55-0.60 (m, 4H), 1.61-1.64 (m, 2H), 1.92-2.16 (m, 11H), 2.53-2.58 (m, 2H), 3.68 (s, 3H), 4.18-4.20 (m, 1H), 5.44-5.68 (m, 2H), 6.42 (s, 1H), 7.24-7.28 (m, 1H) 
     Example 106 
       1 H-NMR (CDCl 3 ) δ 0.36-0.53 (m, 8H), 1.63-1.67 (m, 2H), 1.90-1.94 (m, 2H), 2.00-2.19 (m, 9H), 2.88-2.93 (m, 2H), 3.64 (s, 3H), 4.24-4.26 (m, 1H), 6.18 (bs, 1H), 6.74 (bs, 1H), 7.15-7.17 (m, 1H) 
     Example 107 
       1 H-NMR (CDCl 3 ) δ 0.39-0.43 (m, 2H), 0.55-0.59 (m, 2H), 1.63-1.66 (m, 2H), 1.71-2.11 (m, 10H), 2.14-2.18 (m, 3H), 2.73-2.75 (m, 1H), 3.14-3.18 (m, 2H), 3.30 (s, 3H), 3.37-3.40 (m, 2H), 3.63 (s, 3H), 4.21-4.25 (m, 1H), 5.67-5.74 (m, 1H), 6.13-6.18 (m, 1H), 6.92-6.94 (m, 1H) 
     Example 108 
       1 H-NMR (CDCl 3 ) δ 0.15-0.24 (m, 1H), 0.41-0.56 (m, 2H), 0.61-0.70 (m, 1H), 1.31-2.20 (m, 21H), 2.82-2.87 (m, 1H), 3.67 (s, 3H), 3.74-3.80 (m, 1H), 4.25-4.26 (m, 1H), 6.13-6.27 (m, 1H), 6.68-6.86 (m, 1H), 7.16-7.18 (m, 1H). 
     Example 109 
       1 H-NMR (CDCl 3 ) δ 0.13-0.20 (m, 1H), 0.45-0.55 (m, 2H), 0.67-0.75 (m, 1H), 1.51-1.71 (m, 6H), 1.73-2.20 (m, 11H), 2.84-2.89 (m, 1H), 3.32-3.45 (m, 3H), 3.68 (s, 3H), 3.92-4.03 (m, 2H), 4.23-4.25 (m, 1H), 6.11-6.27 (m, 1H), 6.57-6.70 (m, 1H), 7.15-7.17 (m, 1H) 
     Example 110 
       1 H-NMR (CDCl 3 ) δ 1.05-1.09 (m, 3H), 1.62-1.65 (m, 2H), 1.83-2.07 (m, 9H), 2.18 (brs, 2H), 2.78 (s, 3H), 3.00-3.05 (m, 2H), 3.69 (m, 3H), 4.19-4.23 (m, 1H), 5.23 (s, 1H), 5.62 (s, 1H), 6.90-6.93 (m, 1H) 
     Example 111 
       1 H-NMR (CDCl 3 ) δ 1.58-1.70 (m, 2H), 1.85-2.22 (m, 9H), 2.16-2.22 (m, 2H), 2.22-2.34 (m, 2H), 2.84 (s, 3H), 3.39-3.43 (m, 2H), 4.19-4.23 (m, 1H), 5.29 (s, 1H), 5.62 (s, 1H), 7.07-7.11 (m, 1H) 
     Example 112 
       1 H-NMR (CDCl 3 ) δ 1.55-1.67 (m, 2H), 1.83-2.10 (m, 12H), 2.11-2.19 (m, 2H), 2.20-2.36 (m, 2H), 2.77 (s, 3H), 3.24-3.29 (m, 2H), 3.67 (s, 3H), 4.16-4.23 (m, 1H), 5.42 (s, 1H), 5.80 (s, 1H), 6.87-6.95 (m, 1H) 
     Example 113 
       1 H-NMR (CDCl 3 ) δ 1.57-1.70 (m, 2H), 1.73-2.10 (m, 10H), 2.11-2.29 (m, 2H), 2.91 (s, 3H), 3.60-3.78 (m, 2H), 3.72 (s, 3H), 4.15-4.23 (m, 1H), 5.43 (s, 1H), 5.82 (s, 1H), 6.87-6.97 (m, 1H) 
     Example 114 
       1 H-NMR (CDCl 3 ) δ 1.55-1.78 (m, 6H), 1.93-2.07 (m, 9H), 2.17-2.18 (m, 2H), 2.62 (s, 3H), 2.87-2.95 (m, 1H), 3.31-3.37 (m, 2H), 3.75 (s, 3H), 3.97-4.00 (m, 2H), 4.20-4.21 (m, 1H), 5.26 (bs, 1H), 5.62 (bs, 1H), 6.48 (s, 1H), 7.22-7.24 (m, 1H) 
     Example 115 
       1 H-NMR (DMSO-d 6 ) δ 0.84-0.85 (m, 6H), 1.27-1.32 (m, 2H), 1.46-1.49 (m, 2H), 1.53-1.60 (m, 1H), 1.75-1.98 (m, 11H), 2.71 (s, 3H), 2.94-2.98 (m, 2H), 3.65 (s, 3H), 3.92-3.94 (m, 1H), 6.74 (s, 1H), 7.01 (s, 1H), 7.28-7.30 (m, 1H) 
     Example 116 
       1 H-NMR (CDCl 3 ) δ 1.62-1.66 (m, 2H), 1.89-2.08 (m, 10H), 2.18 (s, 2H), 2.84 (s, 3H), 3.17-3.19 (m, 2H), 3.33 (s, 3H), 3.42-3.44 (m, 2H), 3.72 (s, 3H), 4.21-4.25 (m, 1H), 5.43 (s, 1H), 5.75 (s, 1H), 6.92-6.94 (m, 1H) 
     Example 117 
       1 H-NMR (CDCl 3 ) δ 1.63-1.66 (m, 2H), 1.80-1.96 (m, 4H), 1.99-2.08 (m, 5H), 2.17-2.18 (m, 2H), 2.94 (s, 3H), 3.54-3.61 (m, 2H), 3.74 (s, 3H), 4.20-4.22 (m, 1H), 5.47 (bs, 1H), 5.85 (bs, 1H), 6.92-6.94 (m, 1H) 
     Example 118 
       1 H-NMR (CDCl 3 ) δ 0.41-0.45 (m, 2H), 0.54-0.59 (m, 2H), 1.62-1.66 (m, 2H), 1.90-1.93 (m, 4H), 1.99-2.07 (m, 5H), 2.18-2.19 (m, 2H), 2.79-2.83 (m, 1H), 3.25-3.28 (m, 2H), 3.29 (s, 3H), 3.40-3.43 (m, 2H), 3.64 (s, 3H), 4.22-4.24 (m, 1H), 5.23 (bs, 1H), 5.62 (bs, 1H), 6.92-6.94 (m, 1H) 
     Example 119 
       1 H-NMR (CDCl 3 ) δ 0.88-0.92 (m, 3H), 1.44-1.53 (m, 2H), 1.62-1.65 (m, 2H), 1.89-1.92 (m, 4H), 1.98-2.07 (m, 5H), 2.17-2.18 (m, 2H), 2.76 (s, 3H), 2.92-2.95 (m, 2H), 3.69 (s, 3H), 4.21-4.23 (m, 1H), 5.23 (bs, 1H), 5.62 (bs, 1H), 6.90-6.92 (m, 1H) 
     Example 120 
       1 H-NMR (CDCl 3 ) δ 1.62-1.66 (m, 2H), 1.88-1.92 (m, 4H), 1.98-2.07 (m, 5H), 2.17-2.18 (m, 2H), 2.89 (s, 3H), 3.33-3.47 (m, 2H), 3.73 (s, 3H), 4.20-4.22 (m, 1H), 5.19 (bs, 1H), 5.59 (bs, 1H), 5.69-5.99 (m, 1H), 6.91-6.93 (m, 1H) 
     Example 121 
       1 H-NMR (CDCl 3 ) δ 1.09-1.10 (m, 6H), 1.63-1.66 (m, 2H), 1.91-1.93 (m, 4H), 1.99-2.07 (m, 5H), 2.19 (bs, 2H), 3.21-3.28 (m, 8H), 3.71 (s, 3H), 4.22-4.24 (m, 1H), 5.23 (bs, 1H), 5.63 (bs, 1H), 6.94-6.96 (m, 1H) 
     Example 122 
       1 H-NMR (CDCl 3 ) δ 1.01-1.05 (m, 3H), 1.63-1.65 (m, 2H), 1.90-1.93 (m, 4H), 1.99-2.07 (m, 5H), 2.18 (bs, 2H), 3.07-3.13 (m, 2H), 3.19-3.23 (m, 2H), 3.29 (s, 3H), 3.35-3.38 (m, 2H), 3.71 (s, 3H), 4.22-4.23 (m, 1H), 5.32 (bs, 1H), 5.68 (bs, 1H), 6.93-6.95 (m, 1H) 
     Example 123 
       1 H-NMR (CDCl 3 ) δ 1.63-1.66 (m, 2H), 1.86-1.95 (m, 4H), 1.99-2.07 (m, 5H), 2.18 (bs, 2H), 2.92 (s, 3H), 3.43-3.50 (m, 2H), 3.77 (s, 3H), 4.20-4.22 (m, 1H), 5.22 (bs, 1H), 5.60 (bs, 1H), 5.67-5.97 (m, 1H), 7.08-7.10 (m, 1H) 
     Example 124 
       1 H-NMR (CDCl 3 ) δ 0.07-0.11 (m, 2H), 0.45-0.50 (m, 2H), 0.84-0.89 (m, 1H), 1.62-1.66 (m, 2H), 1.89-1.93 (m, 4H), 1.99-2.07 (m, 5H), 2.18 (bs, 2H), 2.81-2.83 (m, 5H), 3.72 (s, 3H), 4.22-4.23 (m, 1H), 5.24 (bs, 1H), 5.63 (bs, 1H), 6.91-6.93 (m, 1H) 
     
       
         
           
               
               
            
               
                   
               
               
                   
                 [Chemical Formula 85] 
               
               
                   
               
            
           
           
               
            
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
               
            
           
           
               
               
               
               
               
            
               
                 Example No. 
                 R A   
                 R B   
                 R C   
                 R D   
               
               
                   
               
               
                 125 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 CH 3   
                 Cl 
               
               
                   
               
               
                 126 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 CH 3   
                 F 
               
               
                   
               
               
                 127 
                 CH 3   
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 CH 3   
                 Cl 
               
               
                   
               
               
                 128 
                 CH 3   
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 CH 3   
                 F 
               
               
                   
               
               
                 129 
                 CH 3   
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 CH 3   
                 Cl 
               
               
                   
               
               
                 130 
                 CH 3   
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 CH 3   
                 F 
               
               
                   
               
               
                 131 
                 CH 3   
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 CH 3   
                 F 
               
               
                   
               
            
           
         
       
     
     Example 125 
       1 H-NMR (CDCl 3 ) δ 1.00-1.12 (m, 6H), 1.58-1.69 (m, 2H), 1.89-2.12 (m, 9H), 2.13-2.23 (m, 2H), 3.02-3.12 (m, 2H), 3.13-3.31 (m, 6H), 3.75 (s, 3H), 4.18-4.25 (m, 1H), 5.35 (bs, 1H), 5.64 (bs, 1H), 6.52 (s, 1H), 7.18-7.27 (m, 1H) 
     Example 126 
       1 H-NMR (CDCl 3 ) δ 0.39-0.42 (m, 2H), 0.54-0.58 (m, 2H), 1.52-1.55 (m, 2H), 1.71-1.84 (m, 9H), 1.92-1.95 (m, 2H), 2.18-2.22 (m, 3H), 2.72-2.75 (m, 1H), 3.14-3.18 (m, 2H), 3.33 (s, 3H), 3.36-3.39 (m, 2H), 3.61 (s, 3H), 4.18-4.20 (m, 1H), 6.84-6.86 (m, 1H) 
     Example 127 
       1 H-NMR (DMSO-d 6 ) δ 1.36-1.39 (m, 2H), 1.60-1.78 (m, 9H), 1.93-2.00 (m, 4H), 2.10-2.16 (m, 2H), 2.22-2.29 (m, 2H), 2.40 (s, 3H), 3.33 (s, 3H), 3.48 (s, 2H), 3.84-3.86 (m, 1H), 4.45 (s, 1H), 7.13-7.16 (m, 1H), 7.21-7.31 (m, 5H) 
     Example 128 
       1 H-NMR (DMSO-d 6 ) δ 1.36-1.40 (m, 2H), 1.60-1.63 (m, 4H), 1.68-1.79 (m, 5H), 1.92-2.00 (m, 4H), 2.11-2.17 (m, 2H), 2.20-2.27 (m, 2H), 2.43 (s, 3H), 3.34 (s, 3H), 3.39 (s, 2H), 3.84-3.86 (m, 1H), 4.44 (bs, 1H), 7.04-7.06 (m, 1H), 7.09-7.13 (m, 1H), 7.16-7.18 (m, 2H), 7.24-7.28 (m, 2H) 
     Example 129 
       1 H-NMR (CDCl 3 ) δ 1.25-1.57 (m, 5H), 1.74-1.84 (m, 8H), 1.91-1.94 (m, 2H), 2.18-2.22 (m, 3H), 2.80 (s, 3H), 3.28-3.40 (m, 3H), 3.73 (s, 3H), 3.96-3.98 (m, 2H), 4.18-4.19 (m, 1H), 7.01-7.03 (m, 1H) 
     Example 130 
       1 H-NMR (CDCl 3 ) δ 1.53-1.56 (m, 4H), 1.78-1.84 (m, 9H), 1.92-1.95 (m, 2H), 2.18-2.22 (m, 3H), 2.75 (s, 3H), 3.04-0.311 (m, 1H), 3.34-3.40 (m, 2H), 3.69 (s, 3H), 3.97-4.00 (m, 2H), 4.18-4.20 (m, 1H), 6.85-6.87 (m, 1H) 
     Example 131 
       1 H-NMR (CDCl 3 ) δ 0.07-0.11 (m, 2H), 0.44-0.49 (m, 2H), 0.83-0.90 (m, 1H), 1.39 (bs, 1H), 1.52-1.55 (m, 2H), 1.77-1.84 (m, 6H), 1.92-1.94 (m, 2H), 2.18-2.22 (m, 3H), 2.81-2.86 (m, 5H), 3.71 (s, 3H), 4.18-4.20 (m, 1H), 6.83-6.85 (m, 1H) 
     Example 132 
     4-Chloro-N-[(E)-5-hydroxy-2-adamantyl]-1-methyl-5-{methyl[(3S)-piperidin-3-yl]amino}-1H-pyrazole-3-carboxamide 
     
       
         
         
             
             
         
       
     
     Step (i): 
     To an ice-cooled solution of Compound (14.6 g) in THF (180 mL) was added sodium tertiary-butoxide (3.82 g), and the mixture was stirred for 1 hour. Then, thereto was slowly added methyl iodide (2.59 mL) at 0° C., and the mixture was stirred for 6 hours. Then, thereto was added saturated aqueous ammonium chloride solution, and then the mixture was extracted with ethyl acetate. The organic layer was washed with brine, and then dried over magnesium sulfate and concentrated in vacuo. The residue was purified by silica gel chromatography (eluent: hexane/ethyl acetate=1/1) to give Compound II (8.11 g). 
     Step (ii): 
     To a solution of Compound II (4.00 g) in DMF (30.0 mL) was added N-chlorosuccinimide (1.47 g), and the mixture was stirred at 60° C. for 3 hours. Then, thereto was added water, and then the mixture was extracted with ethyl acetate. The organic layer was washed with water and brine, and then dried over magnesium sulfate and concentrated in vacuo. The residue was purified by silica gel chromatography (eluent: hexane/ethyl acetate=1/1) to give Compound III (4.19 g). 
     Step (iii): 
     To a solution of Compound III (4.19 g) in ethanol (48.0 mL) was added 2N lithium hydroxide solution (14.4 mL), and the mixture was stirred at 50° C. for 2 hours. The reaction solution was concentrated in vacuo, and was adjusted to weak acidity by 1N hydrochloric acid and extracted with ethyl acetate. The organic layer was washed with brine, and then dried over magnesium sulfate and concentrated in vacuo to give Compound IV (3.61 g). 
     Step (iv): 
     To a solution of Compound IV (3.45 g) in DMF (80.0 mL) were added (E)-4-aminoadamantan-1-ol (1.70 g), WSCI.HCl (2.43 g), HOBt.H 2 O (1.72 g) and triethylamine (3.54 mL) at room temperature, and the mixture was stirred overnight. Then, thereto was added saturated aqueous ammonium chloride solution, and then the mixture was extracted with ethyl acetate. The organic layer was washed with water and brine, and then dried over magnesium sulfate and concentrated in vacuo. The residue was purified by silica gel chromatography (eluent: chloroform/meththanol=20/1) to give Compound V (3.81 g). 
     Step (v): 
     To a solution of Compound V (3.80 g) in methanol (35.0 mL) was added 10% palladium-carbon (380 mg), and the mixture was stirred at ambient temperature and normal pressure under hydrogen atmosphere for 6 hours. The reaction solution was filtered, and then the filtrate was concentrated in vacuo to give the titled Compound VI (3.00 g) as a white solid. 
       1 H-NMR (CDCl 3 ) δ 1.22-1.36 (m, 1H), 1.43-1.58 (m, 1H), 1.49-1.59 (m, 2H), 1.66-1.88 (m, 7H), 1.88-1.98 (m, 3H), 2.14-2.27 (m, 3H), 2.46-2.58 (m, 2H), 2.81 (s, 3H), 2.94-3.03 (m, 1H), 3.13-3.27 (m, 2H), 3.74 (s, 3H), 4.16-4.22 (m, 1H), 7.03 (d, J=7 Hz, 1H) 
     Compounds of Examples 133-138 were prepared in the similar manner to Example 132. 
     Example 133 
     4-Chloro-N-[(E)-5hydroxy-2-adamantyl]-1-methyl-5-[methyl(piperidin-4-yl)amino]-1H-pyrazole-3-carboxamide 
     
       
         
         
             
             
         
       
     
       1 H-NMR (CDCl 3 ) δ 1.35-1.58 (m, 4H), 1.61-2.10 (m, 12H), 2.10-2.27 (m, 3H), 2.58-2.65 (m, 2H), 2.78 (s, 3H), 3.11-3.15 (m, 2H), 3.70 (s, 3H), 4.15-4.19 (m, 1H), 6.99-7.02 (m, 1H) 
     Example 134 
     4-Chloro-N-[(E)-5-hydroxy-2-adamantyl]-1-methyl-5-[methyl(piperidin-4-ylmethyl)amino]-1H-pyrazole-3-carboxamide 
     
       
         
         
             
             
         
       
     
       1 H-NMR (CDCl 3 ) δ 1.05-1.35 (m, 3H), 1.45-1.60 (m, 3H), 1.63-2.07 (m, 11H), 2.10-2.30 (m, 3H), 2.75 (m, 2H), 2.68-2.90 (s, 3H), 2.91-3.03 (m, 1H), 3.05-3.16 (m, 2H), 3.71 (s, 3H), 4.10-4.21 (m, 1H), 6.95-7.06 (m, 1H) 
     Example 135 
     4-Chloro-N-[(E)-5-hydroxy-2-adamantyl]-1-methyl-5-[methyl(2-piperidin-4-ylethyl)amino]-1H-pyrazole-3-carboxamide 
     
       
         
         
             
             
         
       
     
       1 H-NMR (CDCl 3 ) δ 1.08-1.56 (m, 11H), 1.78-1.94 (m, 10H), 2.18-2.23 (m, 3H), 2.786-2.792 (m, 3H), 2.88-2.97 (m, 2H), 3.10-3.13 (m, 2H), 3.70-3.71 (m, 3H), 4.19-4.20 (m, 1H), 7.01-7.03 (m, 1H) 
     Example 136 
     4-Chloro-N-[(E)-5-hydroxy-2-adamantyl]-1-methyl-5-{methyl[(3R)-pyrrolidin-3-yl]amino}-1H-pyrazole-3-carboxamide 
     
       
         
         
             
             
         
       
     
       1 H-NMR (CDCl 3 ) δ 1.52-1.56 (m, 2H), 1.78-1.85 (m, 8H), 1.92-1.94 (m, 2H), 2.06-2.11 (m, 1H), 2.21 (bs, 3H), 2.63-2.75 (m, 4H), 3.03-3.28 (m, 4H), 3.74 (s, 3H), 3.92-3.95 (m, 1H), 4.15-4.17 (m, 1H), 6.87-6.89 (m, 1H) 
     Example 137 
     4-Chloro-N-[(E)-5-hydroxy-2-adamantyl]-1-methyl-5-{methyl[(3S)-pyrrolidin-3-yl]amino}-1H-pyrazole-3-carboxamide 
     
       
         
         
             
             
         
       
     
       1 H-NMR (CDCl 3 ) δ 1.53-1.97 (m, 13H), 2.12-2.21 (m, 4H), 2.81 (s, 3H), 3.34-3.43 (m, 4H), 3.83 (s, 3H), 4.15-4.17 (m, 1H), 4.32-4.37 (m, 1H), 7.03-7.05 (m, 1H) 
     Example 138 
     4-Chloro-N-[(E)-5-hydroxy-2-adamantyl]-1-methyl-5-{methyl[(3R)-piperidin-3-yl]amino}-1H-pyrazole-3-carboxamide 
     
       
         
         
             
             
         
       
     
       1 H-NMR (CDCl 3 ) δ 1.23-1.32 (m, 1H), 1.40-1.73 (m, 7H), 1.78-1.85 (m, 6H), 1.92-1.94 (m, 3H), 2.18-2.23 (m, 3H), 2.45-2.52 (m, 2H), 2.81 (s, 3H), 3.09-3.20 (m, 2H), 3.73 (s, 3H), 4.18-4.20 (m, 1H), 7.01-7.03 (m, 1H) 
     Example 139 
     4-Fluoro-N-[(E)-5-hydroxy-2-adamantyl]-1-methyl-5-{methyl[(3S)-piperidin-3-yl]amino}-1H-pyrazole-3-carboxamide 
     
       
         
         
             
             
         
       
     
     Step (i): 
     To an ice-cooled solution of Compound I (4.14 g) in DMF (35.0 mL) was added dropwise an aqueous solution (35.0 mL) of 1-chloromethyl-4-fluoro-1,4-diazoniabicyclo[2.2.2.] octane-bis(tetrafluoroborate) (5.76 g), and the mixture was stirred at room temperature for 15 hours. Then, thereto was added water, and then the mixture was extracted with ethyl acetate. The organic layer was washed with water and brine, and then dried over magnesium sulfate and concentrated in vacuo. The residue was purified by silica gel chromatography (eluent: hexane/ethyl acetate=1/1) to give Compound II (2.28 g). 
     Step (ii): 
     A mixed solution of Compound II (2.28 g), ethanol (27.3 mL) and 2N lithium hydroxide solution (8.15 mL) was stirred at 50° C. for 2 hours. The reaction solution was concentrated in vacuo, and was adjusted to weak acidity by 1N hydrochloric acid and extracted with ethyl acetate. The organic layer was washed with brine, and then dried over magnesium sulfate and concentrated in vacuo to give Compound III (2.00 g). 
     Step (iii): 
     A mixed solution of Compound III (2.00 g), (E)-4-aminoadamantan-1-ol (1.03 g), WSCI.HCl (1.47 g), HOBt.H 2 O (1.04 g), triethylamine (2.14 mL) and DMF (45.0 mL) was stirred at room temperature overnight. Then, thereto was added saturated aqueous ammonium chloride solution, and then the mixture was extracted with ethyl acetate. The organic layer was washed with water and brine, and then dried over magnesium sulfate and concentrated in vacuo. The residue was purified by silica gel chromatography (eluent: chloroform/methanol=20/1) to give Compound IV (2.10 g). 
     Step (iv): 
     Compound IV (2.10 g) was dissolved in methanol (30.0 mL), and then thereto was added 10% palladium-carbon (210 mg) and the mixture was stirred under hydrogen atmosphere for 3 hours. The reaction solution was filtered, and then the filtrate was concentrated in vacuo to give the titled Compound V (1.54 g) as a white solid. 
       1 H-NMR (CDCl 3 ) δ 1.24-1.35 (m, 1H), 1.42-1.55 (m, 1H), 1.50-1.58 (m, 2H), 1.70-1.86 (m, 7H), 1.90-2.00 (m, 3H), 2.18-2.22 (m, 3H), 2.42-2.53 (m, 2H), 2.76 (s, 3H), 2.92-3.02 (m, 2H), 3.20-3.26 (m, 1H), 3.68 (s, 3H), 4.15-4.25 (m, 1H), 6.85 (d, J=8 Hz, 1H) 
     Compounds of Examples 140-146 were prepared in the similar manner to Example 139. 
     Example 140 
     4-Fluoro-N-[(E)-5-hydroxy-2-adamantyl-1-methyl-5-[methyl(piperidin-4-ylmethyl)amino]-1H-pyrazole-3-carboxamide 
     
       
         
         
             
             
         
       
     
       1 H-NMR (CDCl 3 ) δ 1.18-1.30 (m, 2H), 1.51-1.59 (m, 2H), 1.55-1.66 (m, 1H), 1.76-1.86 (m, 8H), 1.90-1.97 (m, 2H), 2.10-2.25 (m, 3H), 2.57-2.66 (m, 2H), 2.74 (s, 3H), 2.87-2.93 (m, 2H), 3.13-3.22 (m, 2H), 3.69 (s, 3H), 4.16-4.22 (m, 1H), 6.85 (d, J=8 Hz, 1H) 
     Example 141 
     4-Fluoro-N-[(E)-5-hydroxy-2-adamantyl]-1-methyl-5-{methyl[(3R)-pyrrolidin-3-yl]amino}-1H-pyrazole-3-carboxamide 
     
       
         
         
             
             
         
       
     
       1 H-NMR (CDCl 3 ) δ 1.50-1.57 (m, 2H), 1.58-1.68 (m, 1H), 1.75-1.82 (m, 7H), 1.90-2.21 (m, 2H), 2.15-2.25 (m, 3H), 2.72 (s, 3H), 2.75-2.82 (m, 1H), 2.90-3.11 (m, 3H), 3.69 (s, 3H), 3.72-3.80 (m, 1H), 4.66-4.71 (m, 1H), 6.84 (d, J=8 Hz, 1H) 
     Example 142 
     4-Fluoro-N-[(E)-5-hydroxy-2-adamantyl]-1-methyl-5-[methyl(piperidin-4-yl)amino]-1H-pyrazole-3-carboxamide 
     
       
         
         
             
             
         
       
     
       1 H-NMR (CDCl 3 ) δ 1.37-1.60 (m, 6H), 1.79-1.96 (m, 10H), 2.19-2.23 (m, 3H), 2.57-2.63 (m, 2H), 2.76 (s, 3H), 3.12-3.15 (m, 2H), 3.50 (s, 3H), 3.685-3.693 (m, 1H), 4.19-4.21 (m, 1H), 6.84-6.86 (m, 1H) 
     Example 143 
     4-Fluoro-N-[(E)-5-hydroxy-2-adamantyl]-1-methyl-5-{methyl[(3S)-pyrrolidin-3-yl]amino}-1H-pyrazole-3-carboxamide 
     
       
         
         
             
             
         
       
     
       1 H-NMR (CDCl 3 ) δ 1.53-1.56 (m, 13H), 2.18-2.22 (m, 3H), 2.74-2.77 (m, 4H), 2.94-3.07 (m, 4H), 3.73-3.74 (m, 3H), 3.96-3.99 (m, 1H), 4.18-4.19 (m, 1H), 7.02-7.04 (m, 1H) 
     Example 144 
     4-Fluoro-N-[(E)-5-hydroxy-2-adamantyl]-1-methyl-5-{methyl[(3R)-piperidin-3-yl]amino}-1H-pyrazole-3-carboxamide 
     
       
         
         
             
             
         
       
     
       1 H-NMR (CDCl 3 ) δ 1.46-1.57 (m, 2H), 1.79-1.84 (m, 11H), 1.92-1.95 (m, 4H), 2.03-2.07 (m, 1H), 2.21 (bs, 3H), 2.74-2.81 (m, 4H), 3.28-3.31 (m, 1H), 3.48-3.51 (m, 1H), 3.74 (s, 3H), 4.16-4.17 (m, 1H), 6.89-6.91 (m, 1H) 
     Example 145 
     Benzyl 4-[[4-chloro-3-({[(E)-5-hydroxy-2-adamantyl]amino}carbonyl)-1-methyl-1H-pyrazol-5-yl]-(methyl)amino]piperidine-1-carboxylate 
     
       
         
         
             
             
         
       
     
       1 H-NMR (CDCl 3 ) δ 1.50-1.60 (m, 2H), 1.68-1.97 (m, 12H), 2.15-2.25 (m, 3H), 2.75-2.90 (m, 5H), 3.19-3.30 (m, 1H), 3.70 (s, 3H), 4.05-4.27 (m, 3H), 5.12 (s, 2H), 7.01-7.03 (m, 1H), 7.28-7.40 (m, 5H) 
     Example 146 
     Benzyl 4-{[[4-chloro-3-({[(E)-5-hydroxy-2-adamantyl]amino}carbonyl)-1-methyl-1H-pyrazol-5-yl](methyl)amino]methyl}piperidine-1-carboxylate 
     
       
         
         
             
             
         
       
     
       1 H-NMR (CDCl 3 ) δ 1.48-1.60 (m, 3H), 1.62-1.96 (m, 13H), 2.10-2.27 (m, 3H), 2.65-2.87 (m, 5H), 2.90-3.10 (m, 2H), 3.72 (s, 3H), 4.05-4.30 (m, 3H), 5.12 (s, 2H), 6.98-7.07 (m, 1H), 7.27-7.40 (m, 4H) 
     Example 147 
     4-Chloro-5-[[(3S)-1-(4-chlorobenzoyl)piperidin-3-yl] (methyl)amino]-N-[(E)-5-hydroxy-2-adamantyl]-1-methyl-1H-pyrazole-3-carboxamide 
     
       
         
         
             
             
         
       
     
     Step (i): 
     To a solution of Compound I (20 mg) and triethylamine (20 μL) in THF (1 mL) was added 4-chlorobenzoyl chloride (10 mg), and the mixture was stirred at room temperature overnight. The reaction was quenched by methanol, and then filtered. The filtrate was concentrated in vacuo, and the residue was purified by a reverse phase HPLC (gradient condition 10%-) to give the titled Compound II (18.3 mg). 
       1 H-NMR (CDCl 3 ) δ 1.36-1.42 (m, 2H), 1.52-1.54 (m, 3H), 1.78-1.84 (m, 7H), 1.92-1.94 (m, 3H), 2.19-2.24 (m, 3H), 2.64-3.03 (m, 4H), 3.25-3.29 (m, 1H), 3.62-3.75 (m, 6H), 4.18-4.20 (m, 1H), 7.00-7.01 (m, 1H), 7.29-7.39 (m, 4H) 
     Example 148 
     4-Chloro-5-[{(3S)-1-[(3-fluorophenyl)sulfonyl] piperidin-3-yl}(methyl)amino]-N-[(E)-5-hydroxy-2-adamantyl]-1-methyl-1H-pyrazole-3-carboxamide 
     
       
         
         
             
             
         
       
     
     To a solution of Compound I (20 mg) and triethylamine (20 μL) in THF (1 mL) was added 3-fluorobenzene sulfonyl chloride (11 mg), and the mixture was stirred at room temperature overnight. The reaction was quenched by methanol, and then filtered. The filtrate was concentrated in vacuo, and the residue was purified by a reverse phase HPLC (gradient condition 10%-) to give the titled Compound II (19.1 mg). 
       1 H-NMR (CDCl 3 ) δ 1.27-1.38 (m, 2H), 1.52-1.53 (m, 2H), 1.67-1.85 (m, 9H), 1.91-1.94 (m, 2H), 2.18-2.23 (m, 3H), 2.62-2.72 (m, 2H), 2.82 (s, 3H), 3.28-3.55 (m, 3H), 3.75 (s, 3H), 4.17-4.19 (m, 1H), 7.03-7.05 (m, 1H), 7.28-7.34 (m, 1H), 7.45-7.47 (m, 1H), 7.52-7.57 (m, 2H) 
     Example 149 
     4-[[4-Chloro-3-({[(E)-5-hydroxy-2-adamantyl]amino}carbonyl)-1-methyl-1H-pyrazol-5-yl] (methyl)amino]-N-(2-methoxyphenyl)piperidine-1-carboxamide 
     
       
         
         
             
             
         
       
     
     To an ice-cooled solution of Compound I (20 mg) and triethylamine (20 μL) in THF (3 mL) was added 2-methoxyphenyl isocyanate (9 μL), and the mixture was stirred at room temperature for 2 hours and concentrated in vacuo. Then, the residue was purified by silica gel column chromatography (chloroform/methanol=20/1) and preparative thin-layer chromatography (ethyl acetate) to give the titled Compound II (18 mg). 
       1 H-NMR (CDCl 3 ) δ 1.17-1.60 (m, 5H), 1.66-1.96 (m, 11H), 2.08-2.20 (m, 3H), 2.75 (s, 3H), 2.83-2.91 (m, 2H), 3.20-3.28 (m, 1H), 3.65 (s, 3H), 3.81 (s, 3H), 3.94-4.20 (m, 3H), 6.80-6.95 (m, 4H), 8.00-8.10 (m, 1H) 
     Compounds of Examples 150-160 were prepared in the similar manner. 
     
       
         
           
               
               
            
               
                   
               
               
                   
                 [Chemical Formula 104] 
               
               
                   
               
            
           
           
               
            
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
               
            
           
           
               
               
            
               
                 Example No. 
                 B 2   
               
               
                   
               
               
                 150 
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
               
               
                 151 
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
               
               
                 152 
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
               
               
                 153 
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
               
               
                 154 
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
               
               
                 155 
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
               
               
                 156 
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
               
               
                 157 
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
               
               
                 158 
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
               
               
                 159 
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
               
               
                 160 
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
               
            
           
         
       
     
     Example 150 
       1 H-NMR (CDCl 3 ) δ 1.05-1.18 (m, 3H), 1.25-1.45 (m, 3H), 1.45-1.60 (m, 3H), 1.70-1.96 (m, 12H), 2.72-2.80 (m, 5H), 3.17-3.28 (m, 3H), 3.68 (s, 3H), 3.87-3.91 (s, 2H), 4.15-4.17 (m, 1H), 4.38 (s, 1H), 6.99-7.02 (m, 1H) 
     Example 151 
       1 H-NMR (CDCl 3 ) δ 0.86-0.91 (m, 3H), 1.27-1.58 (m, 5H), 1.60-2.08 (m, 12H), 2.10-2.30 (m, 3H), 2.72-2.85 (m, 5H), 3.10-3.28 (m, 3H), 3.68 (s, 3H), 3.87-3.91 (s, 2H), 4.15-4.18 (m, 1H), 4.46 (s, 1H), 6.99-7.02 (m, 1H) 
     Example 152 
       1 H-NMR (CDCl 3 ) δ 1.00-1.20 (m, 6H), 1.25-1.45 (m, 2H), 1.45-1.96 (m, 13H), 2.10-2.27 (m, 3H), 2.78-2.90 (m, 5H), 3.12-3.27 (m, 1H), 3.68 (s, 3H), 3.80-4.28 (m, 3H), 4.10-4.28 (m, 1H), 6.99-7.02 (m, 1H) 
     Example 153 
       1 H-NMR (CDCl 3 ) δ 1.35-1.64 (m, 5H), 1.78-1.93 (m, 10H), 2.19-2.23 (m, 3H), 2.82 (s, 3H), 2.87-3.00 (m, 2H), 3.25-3.36 (m, 1H), 3.73 (s, 3H), 4.04-4.07 (m, 2H), 4.15-4.23 (m, 1H), 6.37 (s, 1H), 6.96-7.05 (m, 3H), 7.28-7.34 (m, 2H) 
     Example 154 
       1 H-NMR (CDCl 3 ) δ 1.17-1.60 (m, 5H), 1.70-2.10 (m, 11H), 2.14-2.30 (m, 3H), 2.80 (s, 3H), 2.86-3.10 (m, 2H), 3.25-3.40 (m, 1H), 3.71 (s, 3H), 3.78 (s, 3H), 3.92-4.11 (m, 2H), 4.12-4.22 (m, 1H), 6.50-6.70 (m, 1H), 6.77-6.85 (m, 1H), 6.98-7.08 (m, 1H), 7.10-7.20 (m, 2H) 
     Example 155 
       1 H-NMR (CDCl 3 ) δ 1.40-1.58 (m, 5H), 1.72-1.95 (m, 11H), 2.14-2.27 (m, 3H), 2.82 (s, 3H), 2.88-2.94 (m, 2H), 3.25-3.35 (m, 1H), 3.72 (s, 3H), 3.78 (s, 3H), 4.03-4.06 (m, 2H), 4.15-4.22 (m, 1H), 6.83-6.85 (m, 2H), 7.02-7.04 (m, 1H), 7.22-7.24 (m, 2H) 
     Example 156 
       1 H-NMR (CDCl 3 ) δ 1.40-1.60 (m, 5H), 1.70-1.84 (m, 7H), 1.85-2.00 (m, 4H), 2.12-2.23 (m, 3H), 2.81 (s, 3H), 2.93-3.00 (m, 2H), 3.29-3.38 (m, 1H), 3.71 (s, 3H), 4.06-4.09 (m, 2H), 4.13-4.20 (m, 1H), 6.91-6.96 (m, 1H), 6.98-7.05 (m, 1H), 7.21-7.27 (m, 1H), 7.30-7.32 (m, 1H), 8.14-8.16 (m, 1H) 
     Example 157 
       1 H-NMR (CDCl 3 ) δ 1.35-1.58 (m, 5H), 1.70-1.98 (m, 10H), 2.15-2.27 (m, 3H), 2.82 (s, 3H), 2.88-2.96 (m, 2H), 3.25-3.36 (m, 1H), 3.72 (s, 3H), 4.02-4.09 (m, 2H), 4.15-4.22 (m, 1H), 6.38 (s, 1H), 7.00-7.09 (m, 1H), 7.20-7.35 (m, 4H) 
     Example 158 
       1 H-NMR (CDCl 3 ) δ 1.30-1.60 (m, 5H), 1.65-2.00 (m, 10H), 2.09-2.23 (m, 3H), 2.75 (s, 3H), 2.85-2.93 (m, 2H), 3.23-3.30 (m, 1H), 3.66 (s, 3H), 3.98-4.13 (m, 3H), 6.54-6.56 (m, 1H), 6.86-7.05 (m, 4H), 7.96-8.02 (m, 1H) 
     Example 159 
       1 H-NMR (CDCl 3 ) δ 1.34-1.69 (m, 5H), 1.70-2.05 (m, 10H), 2.11-2.28 (m, 3H), 2.80 (s, 3H), 2.88-2.96 (m, 2H), 3.25-3.38 (m, 1H), 3.70 (s, 3H), 4.01-4.20 (m, 3H), 6.43-6.49 (m, 1H), 6.68-6.75 (m, 1H), 6.95-7.03 (m, 2H), 7.15-7.35 (m, 1H) 
     Example 160 
       1 H-NMR (CDCl 3 ) δ 1.27-1.69 (m, 5H), 1.72-1.97 (m, 10H), 2.15-2.25 (m, 3H), 2.83 (s, 3H), 2.92-3.02 (m, 2H), 3.30-3.38 (m, 1H), 3.73 (s, 3H), 4.03-4.20 (m, 3H), 7.00-7.05 (m, 1H), 7.29-7.32 (m, 1H), 7.35-7.39 (m, 1H), 7.52-7.57 (m, 1H), 7.73-7.76 (m, 1H) 
     Example 161 
     4-[[4-Chloro-3-({[(E)-5-hydroxy-2-adamantyl]amino}carbonyl)-1-methyl-1H-pyrazol-5-yl] (methyl)amino]-N-(2,2,2-trifluoroethyl)piperidine-1-carboxamide 
     
       
         
         
             
             
         
       
     
     To an ice-cooled solution of 1,1,1-trifluoroethylamine (4 μL) in THF (3 mL) was added chloro 4-nitrophenyl formate (10 mg), and the mixture was stirred at room temperature for 2 hours. The reaction solution was ice-cooled again, and thereto was added Compound I (20 mg) and the mixture was stirred for 2 hours. Then, thereto was added water, and the mixture was extracted with ethyl acetate. The organic layer was dried over sodium sulfate and concentrated in vacuo. The residue was purified by silica gel chromatography (chloroform/methanol=20/1) to give the titled Compound II (12 mg). 
       1 H-NMR (CDCl 3 ) δ 1.287-1.45 (m, 2H), 1.46-1.58 (m, 2H), 1.72-1.97 (m, 10H), 2.10-2.35 (m, 3H), 2.78-2.98 (m, 5H), 3.20-3.33 (m, 1H), 3.69 (s, 3H), 3.83-4.05 (m, 4H), 4.11-4.22 (m, 1H), 4.85-4.89 (m, 1H), 7.00-7.03 (m, 1H) 
     Compounds of Examples 162-164 were prepared in the similar manner. 
     
       
         
           
               
               
             
               
                   
                   
               
             
            
               
                   
                 [Chemical Formula 106] 
               
               
                   
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
            
           
           
               
               
               
            
               
                   
                 Example No. 
                 B 2   
               
               
                   
                   
               
               
                   
                 **1 
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 **2 
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 **3 
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
            
           
         
       
     
     Example 162 
       1 H-NMR (CDCl 3 ) δ 1.00-1.18 (m, 6H), 1.35-1.70 (m, 2H), 1.72-2.02 (m, 10H), 2.15-2.30 (m, 3H), 2.68-2.90 (m, 6H), 3.00-3.10 (m, 1H), 3.11-3.30 (m, 6H), 3.53-3.70 (m, 2H), 3.72 (s, 3H), 4.15-4.25 (m, 1H), 7.01-7.05 (m, 1H) 
     Example 163 
       1 H-NMR (CDCl 3 ) δ 1.40-1.63 (m, 6H), 1.78-1.97 (m, 9H), 2.15-2.27 (m, 3H), 2.83 (s, 3H), 2.90-3.03 (m, 2H), 3.27-3.38 (m, 1H), 3.73 (s, 3H), 4.09-4.18 (m, 3H), 6.66 (s, 1H), 7.04-7.06 (m, 1H), 7.22-7.25 (m, 1H), 7.96-7.99 (m, 1H), 8.25-8.30 (m, 1H), 8.41-8.46 (m, 1H) 
     Example 164 
       1 H-NMR (CDCl 3 ) δ 1.25-1.43 (m, 2H), 1.48-1.53 (m, 2H), 1.65-2.00 (m, 12H), 2.10-2.22 (m, 3H), 2.70-2.85 (m, 5H), 3.14-3.28 (m, 1H), 3.32 (s, 3H), 3.34-3.48 (m, 3H), 3.67 (s, 3H), 3.88-3.92 (m, 2H), 4.11-4.19 (m, 1H), 6.99-7.02 (m, 1H) 
     Example 165 
     4-Chloro-5-[[1-(5-cyanopyridin-2-yl)piperidin-4-yl] (methyl)amino]-N-[(E)-5-hydroxy-2-adamantyl]-1-methyl-1H-pyrazole-3-carboxamide 
     
       
         
         
             
             
         
       
     
     Compound I (20.0 mg) was dissolved in DMF (1.00 mL), and then thereto were added potassium carbonate (13.0 mg) and 6-chloro-3-pyridinecarbonitrile (10.0 mg) and the mixture was stirred at 100° C. for 12 hours. Then, thereto was added water, and then the mixture was extracted with ethyl acetate. The organic layer was washed with brine, and then dried over sodium sulfate and concentrated in vacuo. The residue was purified by silica gel chromatography (eluent: chloroform/methanol=20/1) to give Compound II (11.0 mg). 
       1 H-NMR (CDCl 3 ) δ 1.34-1.54 (m, 4H), 1.72-2.00 (m, 11H), 2.10-2.30 (m, 3H), 2.79 (s, 3H), 2.90-3.07 (m, 2H), 3.31-3.48 (m, 1H), 3.68 (s, 3H), 4.13-4.17 (m, 1H), 4.36-4.40 (m, 2H), 6.56-6.59 (m, 1H), 7.00-7.03 (m, 1H), 7.55-7.58 (m, 1H), 8.30-8.45 (m, 1H) 
     Example 166 
     4-Chloro-5-[{[1-(5-cyanopyridin-2-yl)piperidin-4-yl]methyl}(methyl)amino]-N-[(E)-5-hydroxy-2-adamantyl]-1-methyl-1H-pyrazole-3-carboxamide 
     
       
         
         
             
             
         
       
     
       1 H-NMR (CDCl 3 ) δ 1.07-1.36 (m, 2H), 1.34-1.60 (m, 3H), 1.70-2.07 (m, 11H), 2.10-2.35 (m, 3H), 2.77 (s, 3H), 2.85-2.93 (m, 2H), 3.00-3.03 (m, 2H), 3.71 (s, 3H), 4.15-4.17 (m, 1H), 4.38-4.43 (m, 2H), 6.55-6.58 (m, 1H), 6.99-7.01 (m, 1H), 7.53-7.57 (m, 1H), 8.30-8.39 (m, 1H) 
     Example 167 
     4-Chloro-N-[(E)-5-hydroxy-2-adamantyl]-1-methyl-5-[methyl(1-pyridin-3-ylpiperidin-4-yl)amino]-1H-pyrazole-3-carboxamide 
     
       
         
         
             
             
         
       
     
     A solution of Compound I (50.0 mg), 3-bromopyridine (22.4 mg), sodium tertiary-butoxide (45.5 mg), 2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (7.30 mg) and tris(dibenzylideneacetone)dipalladium (5.40 mg) in toluene (1.50 mL) was stirred under nitrogen at 100° C. for 3 hours. Then, thereto was added water, and then the mixture was extracted with ethyl acetate. The organic layer was washed with brine, and then dried over magnesium sulfate and concentrated in vacuo. The residue was purified by a reverse phase HPLC (gradient condition 10%-) to give the titled Compound II (28.0 mg). 
       1 H-NMR (CDCl 3 ) δ 1.50-1.68 (m, 4H), 1.76-1.86 (m, 6H), 1.90-2.00 (m, 4H), 2.16-2.25 (m, 3H), 2.75-2.85 (m, 2H), 2.84 (s, 3H), 3.22-3.32 (m, 1H), 3.62-3.70 (m, 2H), 3.73 (s, 3H), 4.16-4.22 (m, 1H), 7.02 (d, J=8 Hz, 1H), 7.12-7.19 (m, 2H), 8.08 (dd, J=2.4 Hz, 1H), 8.29 (d, J=2 Hz, 1H) 
     Compounds of Examples 168-180 were prepared in the similar manner to Example 167. 
     
       
         
           
               
            
               
                   
               
               
                 [Chemical Formula 110] 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
               
            
           
           
               
               
               
            
               
                   
                 Example No. 
                 B 2   
               
               
                   
               
               
                   
                 168 
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
               
               
                   
                 169 
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
               
               
                   
                 170 
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
               
               
                   
                 171 
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
               
               
                   
                 172 
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
               
               
                   
                 173 
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
               
               
                   
                 174 
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
               
               
                   
                 175 
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
               
               
                   
                 176 
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
               
               
                   
                 177 
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
               
               
                   
                 178 
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
               
               
                   
                 179 
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
               
               
                   
                 180 
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
               
               
                   
                 181 
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
               
            
           
         
       
     
     Example 168 
       1 H-NMR (CDCl 3 ) δ 1.45-1.60 (m, 4H), 1.70-1.84 (m, 6H), 1.85-2.10 (m, 5H), 2.10-2.27 (m, 3H), 2.74-2.93 (m, 5H), 3.25-3.35 (m, 1H), 3.65-3.78 (m, 5H), 4.13-4.22 (m, 1H), 7.00-7.03 (m, 1H), 7.29 (s, 1H), 8.27 (s, 1H), 8.41 (s, 1H) 
     Example 169 
       1 H-NMR (CDCl 3 ) δ 1.45-1.62 (m, 4H), 1.62-1.85 (m, 7H), 1.89-2.00 (m, 4H), 2.11-2.25 (m, 3H), 2.81 (s, 3H), 2.83-2.98 (m, 2H), 3.26-3.38 (m, 1H), 3.70 (s, 3H), 3.74-3.79 (m, 2H), 4.13-4.24 (m, 1H), 7.00-7.03 (m, 1H), 7.15-7.18 (m, 1H), 7.46-7.49 (m, 1H), 8.28-8.32 (m, 1H) 
     Example 170 
       1 H-NMR (CDCl 3 ) δ 1.35-1.58 (m, 4H), 1.72-2.00 (m, 11H), 2.11-2.27 (m, 3H), 2.80 (s, 3H), 2.84-2.93 (m, 2H), 3.26-3.38 (m, 1H), 3.69 (s, 3H), 4.12-4.21 (m, 1H), 4.29-4.34 (m, 2H), 6.74-6.77 (m, 1H), 6.88-6.90 (m, 1H), 7.00-7.03 (m, 1H), 7.50-7.56 (m, 1H) 
     Example 171 
       1 H-NMR (CDCl 3 ) δ 1.35-1.70 (m, 5H), 1.70-1.97 (m, 10H), 2.11-2.25 (m, 3H), 2.72-2.90 (m, 5H), 3.20-3.34 (m, 1H), 3.65-3.80 (m, 5H), 4.13-4.21 (m, 1H), 6.89-6.92 (m, 2H), 7.01-7.03 (m, 1H), 7.43-7.46 (m, 2H) 
     Example 172 
       1 H-NMR (CDCl 3 ) δ 1.36-1.57 (m, 5H), 1.70-2.00 (m, 10H), 2.11-2.25 (m, 3H), 2.80 (s, 3H), 2.89-2.97 (m, 2H), 3.30-3.43 (m, 1H), 3.69 (s, 3H), 4.11-4.22 (m, 1H), 4.34-4.38 (m, 2H), 6.61-6.64 (m, 1H), 7.00-7.03 (m, 1H), 7.57-7.61 (m, 1H), 8.35 (s, 1H) 
     Example 173 
       1 H-NMR (CDCl 3 ) δ 1.47-1.70 (m, 5H), 1.75-1.96 (m, 10H), 2.11-2.26 (m, 3H), 2.82 (s, 3H), 2.87-2.95 (m, 2H), 3.17-3.31 (m, 1H), 3.53-3.65 (m, 2H), 4.14-4.22 (m, 1H), 7.00-7.03 (m, 1H), 6.94-7.03 (m, 2H), 7.81-7.86 (m, 1H), 8.38-8.41 (m, 1H) 
     Example 174 
       1 H-NMR (CDCl 3 ) δ 1.39-1.59 (m, 5H), 1.75-2.00 (m, 10H), 2.11-2.25 (m, 3H), 2.75-2.90 (m, 5H), 3.22-3.33 (m, 1H), 3.69 (s, 3H), 4.08-4.22 (m, 3H), 6.58-6.62 (m, 1H), 7.00-7.03 (m, 1H), 7.19-7.25 (m, 1H), 8.00-8.10 (m, 1H) 
     Example 175 
       1 H-NMR (CDCl 3 ) δ 1.49-1.69 (m, 5H), 1.75-1.93 (m, 10H), 2.11-2.25 (m, 3H), 2.68-2.75 (m, 2H), 2.82 (s, 3H), 3.00-3.10 (m, 2H), 3.11-3.25 (m, 1H), 3.74 (s, 3H), 4.13-4.21 (m, 1H), 7.02-7.04 (m, 1H), 7.16-7.21 (m, 1H), 7.28-7.31 (m, 1H), 7.45-7.50 (m, 1H), 7.57-7.60 (m, 1H) 
     Example 176 
       1 H-NMR (CDCl 3 ) δ 1.47-1.69 (m, 5H), 1.72-2.00 (m, 10H), 2.11-2.27 (m, 3H), 2.70-2.90 (m, 5H), 3.20-3.32 (m, 1H), 3.64-3.68 (m, 2H), 3.71 (s, 3H), 4.13-4.21 (m, 1H), 7.01-7.09 (m, 3H), 7.29-7.34 (m, 1H) 
     Example 177 
       1 H-NMR (CDCl 3 ) δ 1.41-1.69 (m, 5H), 1.70-1.98 (m, 10H), 2.10-2.27 (m, 3H), 2.75-2.92 (m, 5H), 3.20-3.35 (m, 1H), 3.62-3.80 (m, 5H), 4.13-4.22 (m, 1H), 6.90-6.92 (m, 2H), 7.01-7.03 (m, 1H), 7.43-7.46 (m, 2H) 
     Example 178 
       1 H-NMR (CDCl 3 ) δ 1.35-1.70 (m, 5H), 1.75-2.02 (m, 10H), 2.12-2.29 (m, 3H), 2.59-2.78 (m, 2H), 2.82 (s, 3H), 3.13-3.28 (m, 1H), 3.38-3.50 (m, 2H), 3.73 (s, 3H), 4.14-4.25 (m, 1H), 6.82-7.14 (m, 5H) 
     Example 179 
       1 H-NMR (CDCl 3 ) δ 1.39-1.69 (m, 5H), 1.70-2.02 (m, 10H), 2.12-2.27 (m, 3H), 2.68-2.90 (m, 5H), 3.17-3.30 (m, 1H), 3.57-3.68 (m, 2H), 3.71 (s, 3H), 4.13-4.25 (m, 1H), 6.50-6.66 (m, 3H), 7.00-7.03 (m, 1H), 7.11-7.19 (m, 1H) 
     Example 180 
       1 H-NMR (CDCl 3 ) δ 1.31-1.62 (m, 5H), 1.70-2.07 (m, 10H), 2.12-2.27 (m, 3H), 2.54-2.80 (m, 2H), 2.82 (s, 3H), 3.11-3.30 (m, 1H), 3.44-3.56 (m, 2H), 3.72 (s, 3H), 4.12-4.24 (m, 1H), 6.70-7.12 (m, 4H) 
     Example 181 
       1 H-NMR (CDCl 3 ) δ 1.35-1.56 (m, 5H), 1.70-1.97 (m, 10H), 2.10-2.27 (m, 3H), 2.80 (s, 3H), 2.86-2.97 (m, 2H), 3.30-3.40 (m, 1H), 3.69 (s, 3H), 4.16-4.18 (m, 1H), 4.29-4.32 (m, 2H), 6.72-6.74 (m, 1H), 6.77 (s, 1H), 7.00-7.31 (m, 1H), 8.24-8.27 (m, 1H) 
     The following Example Compounds, Examples A1-AX9 were prepared in the similar manner to that used in the above Examples. 
     
       
         
         
             
             
         
       
     
     
       
         
           
               
               
               
               
               
             
               
                 TABLE 1 
               
               
                   
               
               
                   
                   
                 obs MS 
                   
                 Measurement 
               
               
                 Ex. No. 
                 —B 
                 [M + 1] 
                 tR (min) 
                 Method 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
               
            
               
                 A1 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 544.4 
                 3.56 
                 SA 
               
               
                   
               
               
                 A2 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 560.5 
                 3.63 
                 SA 
               
               
                   
               
               
                 A3 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 556.4 
                 3.5 
                 SA 
               
               
                   
               
               
                 A4 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 594.4 
                 3.76 
                 SA 
               
               
                   
               
               
                 A5 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 544.5 
                 3.6 
                 SA 
               
               
                   
               
               
                 A6 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 560.5 
                 3.76 
                 SA 
               
               
                   
               
               
                 A7 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 556.5 
                 3.57 
                 SA 
               
               
                   
               
               
                 A8 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 594.4 
                 3.87 
                 SA 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
             
               
                 TABLE 2 
               
               
                   
               
               
                   
                   
                 obs  
                   
                 Measure- 
               
               
                 Ex.  
                   
                 MS 
                 tR 
                 ment 
               
               
                 No. 
                 —B 
                 [M + 1] 
                 (min) 
                 Method 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
               
            
               
                 A9 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 551.5 
                 3.47 
                 SA 
               
               
                   
               
               
                 A10 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 544.6 
                 3.58 
                 SA 
               
               
                   
               
               
                 A11 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 556.4 
                 3.54 
                 SA 
               
               
                   
               
               
                 A12 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 551.7 
                 3.46 
                 SA 
               
               
                   
               
               
                 A13 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 574.6 
                 3.8 
                 SA 
               
               
                   
               
               
                 A14 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 570.4 
                 3.56 
                 SA 
               
               
                   
               
               
                 A15 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 608.5 
                 3.93 
                 SA 
               
               
                   
               
               
                 A16 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 558.5 
                 3.64 
                 SA 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
             
               
                 TABLE 3 
               
               
                   
               
               
                   
                   
                 obs  
                   
                 Measure- 
               
               
                 Ex.  
                   
                 MS 
                 tR 
                 ment 
               
               
                 No. 
                 —B 
                 [M + 1] 
                 (min) 
                 Method 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
               
            
               
                 A17 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 570.5 
                 3.57 
                 SA 
               
               
                   
               
               
                 A18 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 554.6 
                 3.72 
                 SA 
               
               
                   
               
               
                 A19 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 527.6 
                 3.1 
                 SA 
               
               
                   
               
               
                 A20 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 527.7 
                 2.82 
                 SA 
               
               
                   
               
               
                 A21 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 527.6 
                 2.78 
                 SA 
               
               
                   
               
               
                 A22 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 532.6 
                 3.52 
                 SA 
               
               
                   
               
               
                 A23 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 517.5 
                 3.27 
                 SA 
               
               
                   
               
               
                 A24 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 464.4 
                 3.04 
                 SA 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
             
               
                 TABLE 4 
               
               
                   
               
               
                   
                   
                 obs  
                   
                 Measure- 
               
               
                 Ex.  
                   
                 MS 
                 tR 
                 ment 
               
               
                 No. 
                 —B 
                 [M + 1] 
                 (min) 
                 Method 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
               
            
               
                 A25 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 478.4 
                 3.22 
                 SA 
               
               
                   
               
               
                 A26 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 492.7 
                 3.37 
                 SA 
               
               
                   
               
               
                 A27 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 490.6 
                 3.3 
                 SA 
               
               
                   
               
               
                 A28 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 558.5 
                 3.66 
                 SA 
               
               
                   
               
               
                 A29 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 574.6 
                 3.79 
                 SA 
               
               
                   
               
               
                 A30 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 558.5 
                 3.64 
                 SA 
               
               
                   
               
               
                 A31 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 574.5 
                 3.79 
                 SA 
               
               
                   
               
               
                 A32 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 570.4 
                 3.63 
                 SA 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
             
               
                 TABLE 5 
               
               
                   
               
               
                   
                   
                 obs  
                   
                 Measure- 
               
               
                 Ex.  
                   
                 MS 
                 tR 
                 ment 
               
               
                 No. 
                 —B 
                 [M + 1] 
                 (min) 
                 Method 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
               
            
               
                 A33 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 608.5 
                 3.9 
                 SA 
               
               
                   
               
               
                 A34 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 565.5 
                 3.51 
                 SA 
               
               
                   
               
               
                 A35 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 608.3 
                 3.92 
                 SA 
               
               
                   
               
               
                 A36 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 565.5 
                 3.5 
                 SA 
               
               
                   
               
               
                 A37 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 566.4 
                 3.75 
                 SA 
               
               
                   
               
               
                 A38 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 596.4 
                 3.71 
                 SA 
               
               
                   
               
               
                 A39 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 584.4 
                 3.79 
                 SA 
               
               
                   
               
               
                 A40 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 534.6 
                 3.13 
                 SA 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
             
               
                 TABLE 6 
               
               
                   
               
               
                   
                   
                 obs  
                   
                 Measure- 
               
               
                 Ex.  
                   
                 MS 
                 tR 
                 ment 
               
               
                 No. 
                 —B 
                 [M + 1] 
                 (min) 
                 Method 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
               
            
               
                 A41 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 561.5 
                 3.48 
                 SA 
               
               
                   
               
               
                 A42 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 561.5 
                 3.28 
                 SA 
               
               
                   
               
               
                 A43 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 541.3 
                 3.1 
                 SA 
               
               
                   
               
               
                 A44 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 557.4 
                 3.49 
                 SA 
               
               
                   
               
               
                 A45 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 541.4 
                 3.06 
                 SA 
               
               
                   
               
               
                 A46 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 557.3 
                 3.37 
                 SA 
               
               
                   
               
               
                 A47 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 541.5 
                 2.78 
                 SA 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
             
               
                 TABLE 7 
               
               
                   
               
               
                   
                   
                 obs  
                   
                 Measure- 
               
               
                 Ex.  
                   
                 MS 
                 tR 
                 ment 
               
               
                 No. 
                 —B 
                 [M + 1] 
                 (min) 
                 Method 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
               
            
               
                 A49 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 541.7 
                 2.78 
                 SA 
               
               
                   
               
               
                 A50 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 541.3 
                 2.77 
                 SA 
               
               
                   
               
               
                 A51 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 532.4 
                 3.45 
                 SA 
               
               
                   
               
               
                 A52 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 528 
                 3.09 
                 SA 
               
               
                   
               
               
                 A53 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 529.5 
                 3.51 
                 SA 
               
               
                   
               
               
                 A54 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 594.4 
                 3.9 
                 SA 
               
               
                   
               
               
                 A55 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 560.5 
                 3.78 
                 SA 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
               
             
               
                   
                 TABLE 8 
               
               
                   
                   
               
               
                   
                   
                   
                 obs  
                   
                 Measure- 
               
               
                   
                 Ex.  
                   
                 MS 
                 tR 
                 ment 
               
               
                   
                 No. 
                 —B 
                 [M + 1] 
                 (min) 
                 Method 
               
               
                   
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
               
               
            
               
                   
                 B1 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 580.4 
                 3.89 
                 SA 
               
               
                   
                   
               
               
                   
                 B2 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 596.4 
                 3.99 
                 SA 
               
               
                   
                   
               
               
                   
                 B3 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 592.4 
                 3.77 
                 SA 
               
               
                   
                   
               
               
                   
                 B4 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 630.5 
                 4.1 
                 SA 
               
               
                   
                   
               
               
                   
                 B5 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 587.5 
                 3.76 
                 SA 
               
               
                   
                   
               
               
                   
                 B6 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 580.4 
                 3.94 
                 SA 
               
               
                   
                   
               
               
                   
                 B7 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 596.4 
                 4.11 
                 SA 
               
               
                   
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
             
               
                 TABLE 9 
               
               
                   
               
               
                 Ex. 
                   
                 obs MS 
                 tR 
                 Measurement 
               
               
                 No. 
                 —B 
                 [M + 1] 
                 (min) 
                 Method 
               
               
                   
               
             
            
               
                 B9  
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 630.3 
                 4.21 
                 SA 
               
               
                   
               
               
                 B10 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 587.5 
                 3.82 
                 SA 
               
               
                   
               
               
                 B11 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 580.4 
                 3.92 
                 SA 
               
               
                   
               
               
                 B12 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 596.4 
                 4.11 
                 SA 
               
               
                   
               
               
                 B13 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 592.4 
                 3.88 
                 SA 
               
               
                   
               
               
                 B14 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 630.5 
                 4.23 
                 SA 
               
               
                   
               
               
                 B15 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 587.5 
                 3.85 
                 SA 
               
               
                   
               
               
                 B16 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 563.6 
                 3.52 
                 SA 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
             
               
                 TABLE 10 
               
               
                   
               
               
                 Ex. 
                   
                 obs MS 
                 tR 
                 Measurement 
               
               
                 No. 
                 —B 
                 [M + 1] 
                 (min) 
                 Method 
               
               
                   
               
             
            
               
                 B17 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 594.4 
                 3.89 
                 SA 
               
               
                   
               
               
                 B18 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 610.3 
                 4.05 
                 SA 
               
               
                   
               
               
                 B19 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 563.6 
                 3.47 
                 SA 
               
               
                   
               
               
                 B20 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 500.5 
                 3.3 
                 SA 
               
               
                   
               
               
                 B21 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 514.5 
                 3.42 
                 SA 
               
               
                   
               
               
                 B22 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 528.5 
                 3.6 
                 SA 
               
               
                   
               
               
                 B23 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 568.5 
                 3.77 
                 SA 
               
               
                   
               
               
                 B24 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 526.3 
                 3.5 
                 SA 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
               
             
               
                   
                 TABLE 11 
               
               
                   
                   
               
               
                   
                   
                   
                 obs MS 
                   
                 Measurement 
               
               
                   
                 Ex. No. 
                 —B 
                 [M + 1] 
                 tR (min) 
                 Method 
               
               
                   
                   
               
             
            
               
                   
                 B25 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 528.6 
                 3.57 
                 SA 
               
               
                   
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
             
               
                 TABLE 12 
               
               
                   
               
               
                 Ex. 
                   
                 obs MS 
                 tR 
                 Measurement 
               
               
                 No. 
                 —B 
                 [M + 1] 
                 (min) 
                 Method 
               
               
                   
               
             
            
               
                 C1 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 575.4 
                 3.51 
                 SA 
               
               
                   
               
               
                 C2 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 493.6 
                 3.29 
                 SA 
               
               
                   
               
               
                 C3 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 535.5 
                 3.2 
                 SA 
               
               
                   
               
               
                 C4 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 479.5 
                 3.03 
                 SA 
               
               
                   
               
               
                 C5 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 542.4 
                 2.85 
                 SA 
               
               
                   
               
               
                 C6 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 542.4 
                 2.82 
                 SA 
               
               
                   
               
               
                 C7 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 505.6 
                 3.17 
                 SA 
               
               
                   
               
               
                 C8 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 566.5 
                 3.47 
                 SA 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
             
               
                 TABLE 13 
               
               
                   
               
               
                 Ex. 
                   
                 obs MS 
                 tR 
                 Measurement 
               
               
                 No. 
                 —B 
                 [M + 1] 
                 (min) 
                 Method 
               
               
                   
               
             
            
               
                 C9  
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 577.5 
                 3.62 
                 SA 
               
               
                   
               
               
                 C10 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 577.6 
                 3.75 
                 SA 
               
               
                   
               
               
                 C11 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 577.6 
                 3.91 
                 SA 
               
               
                   
               
               
                 C12 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 577.6 
                 3.81 
                 SA 
               
               
                   
               
               
                 C13 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 577.5 
                 3.49 
                 SA 
               
               
                   
               
               
                 C14 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 566.7 
                 3.61 
                 SA 
               
               
                   
               
               
                 C15 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 560.5 
                 3.2 
                 SA 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
             
               
                 TABLE 14 
               
               
                   
               
               
                 Ex. No. 
                 —B 
                 obs MS [M + 1] 
                 tR (min) 
                 Measurement Method 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
               
            
               
                 C17 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 569.8 
                 3.88 
                 SB 
               
               
                   
               
               
                 C18 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 569.8 
                 3.92 
                 SB 
               
               
                   
               
               
                 C19 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 573.7 
                 3.8 
                 SB 
               
               
                   
               
               
                 C20 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 573.7 
                 3.76 
                 SB 
               
               
                   
               
               
                 C21 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 589.7 
                 3.92 
                 SB 
               
               
                   
               
               
                 C22 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 585.7 
                 3.8 
                 SB 
               
               
                   
               
               
                 C23 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 585.7 
                 3.72 
                 SB 
               
               
                   
               
               
                 C24 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 573.4 
                 3.21 
                 SB 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
             
               
                 TABLE 15 
               
               
                   
               
               
                 Ex. No. 
                 —B 
                 obs MS [M + 1] 
                 tR (min) 
                 Measurement Method 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
               
            
               
                 C25 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 589.4 
                 3.3 
                 SB 
               
               
                   
               
               
                 C26 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 589.4 
                 3.34 
                 SB 
               
               
                   
               
               
                 C27 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 585.2 
                 3.15 
                 SB 
               
               
                   
               
               
                 C28 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 556.3 
                 2.51 
                 SB 
               
               
                   
               
               
                 C29 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 610.4 
                 3.32 
                 SB 
               
               
                   
               
               
                 C30 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 572.3 
                 2.82 
                 SB 
               
               
                   
               
               
                 C31 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 560.2 
                 2.99 
                 SB 
               
               
                   
               
               
                 C32 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 576.2 
                 3.13 
                 SB 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
             
               
                 TABLE 16 
               
               
                   
               
               
                 Ex. 
                   
                 obs MS 
                 tR 
                 Measurement 
               
               
                 No. 
                 —B 
                 [M + 1] 
                 (min) 
                 Method 
               
               
                   
               
             
            
               
                 C33 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 556.3 
                 2.53 
                 SB 
               
               
                   
               
               
                 C34 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 595.5 
                 3.37 
                 SB 
               
               
                   
               
               
                 C35 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 569.5 
                 3.26 
                 SB 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
             
               
                 TABLE 17 
               
               
                   
               
               
                   
                   
                 obs MS 
                   
                 Measurement 
               
               
                 Ex. No. 
                 —B 
                 [M + 1] 
                 tR (min) 
                 Method 
               
               
                   
               
             
            
               
                 D1 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 524.5 
                 4.03 
                 SA 
               
               
                   
               
               
                 D2 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 534.6 
                 4.42 
                 SA 
               
               
                   
               
               
                 D3 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 534.6 
                 3.97 
                 SA 
               
               
                   
               
               
                 D4 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 534.7 
                 4.44 
                 SA 
               
               
                   
               
               
                 D5 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 517.5 
                 3.10 
                 SA 
               
               
                   
               
               
                 D6 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 567.5 
                 3.16 
                 SA 
               
               
                   
               
               
                 D7 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 534.5 
                 4.40 
                 SA 
               
               
                   
               
               
                 D8 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 500.5 
                 3.36 
                 SA 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
             
               
                 TABLE 18 
               
               
                   
               
               
                   
                   
                 obs MS 
                   
                 Measurement 
               
               
                 Ex. No. 
                 —B 
                 [M + 1] 
                 tR (min) 
                 Method 
               
               
                   
               
             
            
               
                 D9  
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 530.5 
                 2.82 
                 SA 
               
               
                   
               
               
                 D10 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 499.6 
                 2.82 
                 SA 
               
               
                   
               
            
           
         
       
     
     
       
         
         
             
             
         
       
     
     
       
         
           
               
               
               
               
               
             
               
                 TABLE 19 
               
               
                   
               
               
                 Ex. 
                   
                 obs MS 
                 tR 
                 Measurement 
               
               
                 No. 
                 —B 
                 [M + 1] 
                 (min) 
                 Method 
               
               
                   
               
             
            
               
                 E1 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 544.5 
                 3.72 
                 SA 
               
               
                   
               
               
                 E2 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 528.6 
                 3.55 
                 SA 
               
               
                   
               
               
                 E3 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 540.5 
                 3.49 
                 SA 
               
               
                   
               
               
                 E4 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 592.5 
                 3.89 
                 SA 
               
               
                   
               
               
                 E5 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 542.3 
                 3.57 
                 SA 
               
               
                   
               
               
                 E6 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 558.5 
                 3.73 
                 SA 
               
               
                   
               
               
                 E7 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 554.6 
                 3.51 
                 SA 
               
               
                   
               
               
                 E8 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 554.6 
                 3.5  
                 SA 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
             
               
                 TABLE 20 
               
               
                   
               
               
                 Ex. 
                   
                 obs MS 
                 tR 
                 Measurement 
               
               
                 No. 
                 —B 
                 [M + 1] 
                 (min) 
                 Method 
               
               
                   
               
             
            
               
                 E9  
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 580.5 
                 3.68 
                 SA 
               
               
                   
               
               
                 E10 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 568.6 
                 3.73 
                 SA 
               
               
                   
               
               
                 E11 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 584.4 
                 3.91 
                 SA 
               
               
                   
               
               
                 E12 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 541.4 
                 3.32 
                 SA 
               
               
                   
               
               
                 E13 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 579.6 
                 3.59 
                 SA 
               
               
                   
               
               
                 E14 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 545.6 
                 3.44 
                 SA 
               
               
                   
               
               
                 E15 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 579.6 
                 3.61 
                 SA 
               
               
                   
               
               
                 E16 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 550.4 
                 3.73 
                 SA 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
             
               
                 TABLE 21 
               
               
                   
               
               
                   
                   
                 obs MS 
                   
                 Measurement 
               
               
                 Ex. No. 
                 —B 
                 [M + 1] 
                 tR (min) 
                 Method 
               
               
                   
               
             
            
               
                 E17 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 516.5 
                 3.39 
                 SA 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
             
               
                 TABLE 22 
               
               
                   
               
               
                 Ex. 
                   
                 obs MS 
                 tR 
                 Measurement 
               
               
                 No. 
                 —B 
                 [M + 1] 
                 (min) 
                 Method 
               
               
                   
               
             
            
               
                 F1 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 580.4 
                 4.01 
                 SA 
               
               
                   
               
               
                 F2 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 580.4 
                 4.02 
                 SA 
               
               
                   
               
               
                 F3 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 564.5 
                 3.79 
                 SA 
               
               
                   
               
               
                 F4 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 564.4 
                 3.86 
                 SA 
               
               
                   
               
               
                 F5 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 564.4 
                 3.84 
                 SA 
               
               
                   
               
               
                 F6 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 576.6 
                 3.97 
                 SA 
               
               
                   
               
               
                 F7 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 576.7 
                 3.79 
                 SA 
               
               
                   
               
               
                 F8 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 614.5 
                 4.1  
                 SA 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
             
               
                 TABLE 23 
               
               
                   
               
               
                 Ex. 
                   
                 obs MS 
                 tR 
                 Measurement 
               
               
                 No. 
                 —B 
                 [M + 1] 
                 (min) 
                 Method 
               
               
                   
               
             
            
               
                 F9  
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 614.5 
                 4.15 
                 SA 
               
               
                   
               
               
                 F10 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 571.4 
                 3.73 
                 SA 
               
               
                   
               
               
                 F11 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 582.4 
                 3.89 
                 SA 
               
               
                   
               
               
                 F12 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 582.1 
                 3.53 
                 SB 
               
               
                   
               
               
                 F13 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 582.1 
                 3.44 
                 SB 
               
               
                   
               
               
                 F14 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 582.3 
                 3.94 
                 SA 
               
               
                   
               
               
                 F15 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 582.6 
                 3.79 
                 SA 
               
               
                   
               
               
                 F16 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 578.5 
                 3.81 
                 SA 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
             
               
                 TABLE 24 
               
               
                   
               
               
                   
                   
                 obs MS 
                   
                 Measurement 
               
               
                 Ex. No. 
                 —B 
                 [M + 1] 
                 tR (min) 
                 Method 
               
               
                   
               
             
            
               
                 F17 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 594.4 
                 3.96 
                 SA 
               
               
                   
               
               
                 F18 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 552.1 
                 3.28 
                 SB 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
             
               
                 TABLE 25 
               
               
                   
               
               
                 Ex. 
                   
                 obs MS 
                 tR 
                 Measurement 
               
               
                 No. 
                 —B 
                 [M + 1] 
                 (min) 
                 Method 
               
               
                   
               
             
            
               
                 G1 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 559.4 
                 3.24 
                 SB 
               
               
                   
               
               
                 G2 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 559.4 
                 3.36 
                 SB 
               
               
                   
               
               
                 G3 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 559.4 
                 3.34 
                 SB 
               
               
                   
               
               
                 G4 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 543.4 
                 3.13 
                 SB 
               
               
                   
               
               
                 G5 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 543.4 
                 3.21 
                 SB 
               
               
                   
               
               
                 G6 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 543.4 
                 3.15 
                 SB 
               
               
                   
               
               
                 G7 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 555.2 
                 3.19 
                 SB 
               
               
                   
               
               
                 G8 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 555.5 
                 3.13 
                 SB 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
             
               
                 TABLE 26 
               
               
                   
               
               
                 Ex. 
                   
                 obs MS 
                 tR 
                 Measurement 
               
               
                 No. 
                 —B 
                 [M + 1] 
                 (min) 
                 Method 
               
               
                   
               
             
            
               
                 G9  
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 555.2 
                 3.05 
                 SB 
               
               
                   
               
               
                 G10 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 561.4 
                 3.21 
                 SB 
               
               
                   
               
               
                 G11 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 561.4 
                 3.32 
                 SB 
               
               
                   
               
               
                 G12 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 561.4 
                 3.24 
                 SB 
               
               
                   
               
               
                 G13 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 561.4 
                 3.38 
                 SB 
               
               
                   
               
               
                 G14 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 561.4 
                 3.01 
                 SB 
               
               
                   
               
               
                 G15 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 550.4 
                 2.99 
                 SB 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
             
               
                 TABLE 27 
               
               
                   
               
               
                 Ex. 
                   
                 obs MS 
                 tR 
                 Measurement 
               
               
                 No. 
                 —B 
                 [M + 1] 
                 (min) 
                 Method 
               
               
                   
               
             
            
               
                 G17 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 550.4 
                 3.13 
                 SB 
               
               
                   
               
               
                 G18 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 557.4 
                 3.11 
                 SB 
               
               
                   
               
               
                 G19 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 557.2 
                 3.11 
                 SB 
               
               
                   
               
               
                 G20 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 557.4 
                 3.11 
                 SB 
               
               
                   
               
               
                 G21 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 573.4 
                 3.21 
                 SB 
               
               
                   
               
               
                 G22 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 573.4 
                 3.26 
                 SB 
               
               
                   
               
               
                 G23 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 573.4 
                 3.26 
                 SB 
               
               
                   
               
               
                 G24 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 553.2 
                 3.19 
                 SB 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
             
               
                 TABLE 28 
               
               
                   
               
               
                 Ex. No. 
                 —B 
                 obs MS [M + 1] 
                 tR (min) 
                 Measurement Method 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
               
            
               
                 G25 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 553.2 
                 3.21 
                 SB 
               
               
                   
               
               
                 G26 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 569.5 
                 3.11 
                 SB 
               
               
                   
               
               
                 G27 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 569.8 
                 3.67 
                 SB 
               
               
                   
               
               
                 G28 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 569.5 
                 3.07 
                 SB 
               
               
                   
               
               
                 G29 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 540.4 
                 2.4 
                 SB 
               
               
                   
               
               
                 G30 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 594.4 
                 3.21 
                 SB 
               
               
                   
               
               
                 G31 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 556.3 
                 2.71 
                 SB 
               
               
                   
               
               
                 G32 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 544.3 
                 2.82 
                 SB 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
             
               
                 TABLE 29 
               
               
                   
               
               
                 Ex. 
                   
                 obs MS 
                 tR 
                 Measurement 
               
               
                 No. 
                 —B 
                 [M + 1] 
                 (min) 
                 Method 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
               
            
               
                 G33 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 560.2 
                 3.03 
                 SB 
               
               
                   
               
               
                 G34 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 540.4 
                 2.51 
                 SB 
               
               
                   
               
               
                 G35 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 579.3 
                 3.26 
                 SB 
               
               
                   
               
               
                 G36 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 553.2 
                 3.17 
                 SB 
               
               
                   
               
               
                 G37 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 526.4 
                 2.4 
                 SB 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
             
               
                 TABLE 30 
               
               
                   
               
               
                   
                   
                 obs MS 
                   
                 Measurement 
               
               
                 Ex. No. 
                 —B 
                 [M + 1] 
                 tR (min) 
                 Method 
               
               
                   
               
             
            
               
                 H1 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 551.3 
                 3.53 
                 SB 
               
               
                   
               
               
                 H2 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 508.4 
                 3.19 
                 SB 
               
               
                   
               
               
                 H3 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 551.3 
                 3.86 
                 SB 
               
               
                   
               
               
                 H4 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 508.4 
                 3.49 
                 SB 
               
               
                   
               
               
                 H5 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 551.3 
                 3.19 
                 SB 
               
               
                   
               
               
                 H6 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 508.4 
                 3.11 
                 SB 
               
               
                   
               
               
                 H7 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 551.3 
                 3.38 
                 SB 
               
               
                   
               
               
                 H8 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 508.4 
                 3.26 
                 SB 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
             
               
                 TABLE 31 
               
               
                   
               
               
                   
                   
                 obs MS 
                   
                 Measurement 
               
               
                 Ex. No. 
                 —B 
                 [M + 1] 
                 tR (min) 
                 Method 
               
               
                   
               
             
            
               
                 H9  
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 501.4 
                 2.71 
                 SB 
               
               
                   
               
               
                 H10 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 514.3 
                 2.36 
                 SB 
               
               
                   
               
               
                 H11 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 484.6 
                 2.84 
                 SB 
               
               
                   
               
            
           
         
       
     
     
       
         
         
             
             
         
       
     
     
       
         
           
               
               
               
               
               
             
               
                 TABLE 32 
               
               
                   
               
               
                   
                   
                 obs MS 
                   
                 Measurement 
               
               
                 Ex. No. 
                 —B 
                 [M + 1] 
                 tR (min) 
                 Method 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
               
            
               
                 I1 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 558.5 
                 3.67 
                 SA 
               
               
                   
               
               
                 I2 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 574.6 
                 3.76 
                 SA 
               
               
                   
               
               
                 I3 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 570.5 
                 3.61 
                 SA 
               
               
                   
               
               
                 I4 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 608.5 
                 3.87 
                 SA 
               
               
                   
               
               
                 I5 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 558.5 
                 3.72 
                 SA 
               
               
                   
               
               
                 I6 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 574.6 
                 3.88 
                 SA 
               
               
                   
               
               
                 I7 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 570.5 
                 3.7 
                 SA 
               
               
                   
               
               
                 I8 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 608.5 
                 4 
                 SA 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
             
               
                 TABLE 33 
               
               
                   
               
               
                 Ex. 
                   
                 obs MS 
                 tR 
                 Measurement 
               
               
                 No. 
                 —B 
                 [M + 1] 
                 (min) 
                 Method 
               
               
                   
               
             
            
               
                 I9  
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 565.6 
                 3.59 
                 SA 
               
               
                   
               
               
                 I10 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 558.5 
                 3.72 
                 SA 
               
               
                   
               
               
                 I11 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 574.6 
                 3.91 
                 SA 
               
               
                   
               
               
                 I12 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 570.5 
                 3.67 
                 SA 
               
               
                   
               
               
                 I13 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 608.5 
                 4.03 
                 SA 
               
               
                   
               
               
                 I14 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 565.5 
                 3.61 
                 SA 
               
               
                   
               
               
                 I15 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 588.4 
                 3.93 
                 SA 
               
               
                   
               
               
                 I16 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 584.4 
                 3.69 
                 SA 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
             
               
                 TABLE 34 
               
               
                   
               
               
                   
                   
                   
                   
                 Measure- 
               
               
                 Ex. 
                   
                 obs MS 
                 tR 
                 ment 
               
               
                 No. 
                 —B 
                 [M + 1] 
                 (min) 
                 Method 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
               
            
               
                 I17 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 622.4 
                 4.04 
                 SA 
               
               
                   
               
               
                 I18 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 572.5 
                 3.75 
                 SA 
               
               
                   
               
               
                 I19 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 584.5 
                 3.71 
                 SA 
               
               
                   
               
               
                 I20 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 568.6 
                 3.85 
                 SA 
               
               
                   
               
               
                 I21 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 541.5 
                 3.21 
                 SA 
               
               
                   
               
               
                 I22 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 541.5 
                 2.93 
                 SA 
               
               
                   
               
               
                 I23 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 492.5 
                 3.35 
                 SA 
               
               
                   
               
               
                 I24 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 506.5 
                 3.5 
                 SA 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
             
               
                 TABLE 35 
               
               
                   
               
               
                 Ex. 
                   
                 obs MS 
                 tR 
                 Measurement 
               
               
                 No. 
                 —B 
                 [M + 1] 
                 (min) 
                 Method 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
               
            
               
                 I25 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 504.6 
                 3.43 
                 SA 
               
               
                   
               
               
                 I26 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 572.5 
                 3.76 
                 SA 
               
               
                   
               
               
                 I27 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 588.5 
                 3.92 
                 SA 
               
               
                   
               
               
                 I28 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 564.4 
                 3.6 
                 SA 
               
               
                   
               
               
                 I29 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 572.6 
                 3.79 
                 SA 
               
               
                   
               
               
                 I30 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 588.5 
                 3.9 
                 SA 
               
               
                   
               
               
                 I31 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 584.4 
                 3.75 
                 SA 
               
               
                   
               
               
                 I32 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 579.6 
                 3.62 
                 SA 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
             
               
                 TABLE 36 
               
               
                   
               
               
                 Ex. 
                   
                 obs MS 
                 tR 
                 Measurement 
               
               
                 No. 
                 —B 
                 [M + 1] 
                 (min) 
                 Method 
               
               
                   
               
             
            
               
                 I33 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 579.6 
                 3.61 
                 SA 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
             
               
                 TABLE 37 
               
               
                   
               
               
                   
                   
                 obs MS 
                   
                 Measurement 
               
               
                 Ex. No. 
                 —B 
                 [M + 1] 
                 tR (min) 
                 Method 
               
               
                   
               
             
            
               
                 J1 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 594.5 
                 4.02 
                 SA 
               
               
                   
               
               
                 J2 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 610.4 
                 4.13 
                 SA 
               
               
                   
               
               
                 J3 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 606.6 
                 3.89 
                 SA 
               
               
                   
               
               
                 J4 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 644.5 
                 4.22 
                 SA 
               
               
                   
               
               
                 J5 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 601.5 
                 3.89 
                 SA 
               
               
                   
               
               
                 J6 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 594.4 
                 4.08 
                 SA 
               
               
                   
               
               
                 J7 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 610.3 
                 4.24 
                 SA 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
             
               
                 TABLE 38 
               
               
                   
               
               
                 Ex. 
                   
                 obs MS 
                 tR 
                 Measurement 
               
               
                 No. 
                 —B 
                 [M + 1] 
                 (min) 
                 Method 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
               
            
               
                 J9  
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 644.4 
                 4.31 
                 SA 
               
               
                   
               
               
                 J10 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 601.5 
                 3.94 
                 SA 
               
               
                   
               
               
                 J11 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 594.4 
                 4.05 
                 SA 
               
               
                   
               
               
                 J12 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 612.4 
                 4.12 
                 SA 
               
               
                   
               
               
                 J13 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 606.4 
                 4 
                 SA 
               
               
                   
               
               
                 J14 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 644.4 
                 4.35 
                 SA 
               
               
                   
               
               
                 J15 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 601.5 
                 3.95 
                 SA 
               
               
                   
               
               
                 J16 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 608.5 
                 4.01 
                 SA 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
             
               
                   
               
               
                 Ex. 
                   
                 obs MS 
                 tR  
                 Measurement 
               
               
                 No. 
                 —B 
                 [M + 1] 
                 (min) 
                 Method 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
               
            
               
                 J17 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 624.4 
                 4.18 
                 SA 
               
               
                   
               
               
                 J18 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 577.4 
                 3.57 
                 SA 
               
               
                   
               
               
                 J19 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 514.6 
                 3.42 
                 SA 
               
               
                   
               
               
                 J20 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 528.5 
                 3.56 
                 SA 
               
               
                   
               
               
                 J21 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 542.3 
                 3.75 
                 SA 
               
               
                   
               
               
                 J22 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 582.3 
                 3.9 
                 SA 
               
               
                   
               
               
                 J23 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 540.6 
                 3.65 
                 SA 
               
               
                   
               
               
                 J24 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 542.4 
                 3.71 
                 SA 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
             
               
                 TABLE 40 
               
               
                   
               
               
                 Ex. 
                   
                 obs MS 
                 tR 
                 Measurement 
               
               
                 No. 
                 —B 
                 [M + 1] 
                 (min) 
                 Method 
               
               
                   
               
             
            
               
                 K1 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 573.6 
                 3.73 
                 SA 
               
               
                   
               
               
                 K2 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 573.5 
                 3.86 
                 SA 
               
               
                   
               
               
                 K3 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 573.4 
                 3.78 
                 SA 
               
               
                   
               
               
                 K4 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 589.5 
                 3.93 
                 SA 
               
               
                   
               
               
                 K5 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 589.5 
                 4.02 
                 SA 
               
               
                   
               
               
                 K6 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 585.3 
                 3.84 
                 SA 
               
               
                   
               
               
                 K7 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 585.4 
                 3.74 
                 SA 
               
               
                   
               
               
                 K8 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 585.4 
                 3.65 
                 SA 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
             
               
                 TABLE 41 
               
               
                   
               
               
                 Ex. 
                   
                 obs MS 
                 tR 
                 Measurement 
               
               
                 No. 
                 —B 
                 [M + 1] 
                 (min) 
                 Method 
               
               
                   
               
             
            
               
                 K9 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 580.4 
                 3.73 
                 SA 
               
               
                   
               
               
                 K10 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 580.5 
                 3.72 
                 SA 
               
               
                   
               
               
                 K11 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 493.6 
                 3.14 
                 SA 
               
               
                   
               
               
                 K12 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 561.6 
                 3.5  
                 SA 
               
               
                   
               
               
                 K13 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 543.6 
                 3.39 
                 SA 
               
               
                   
               
               
                 K14 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 580.5 
                 3.59 
                 SA 
               
               
                   
               
               
                 K15 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 591.5 
                 3.75 
                 SA 
               
               
                   
               
               
                 K16 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 591.5 
                 3.88 
                 SA 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
             
               
                 TABLE 42 
               
               
                   
               
               
                   
                   
                   
                   
                 Measure- 
               
               
                 Ex. 
                   
                 obs MS 
                 tR 
                 ment 
               
               
                 No. 
                 —B 
                 [M + 1] 
                 (min) 
                 Method 
               
               
                   
               
             
            
               
                 K17 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 591.4 
                 4.01 
                 SA 
               
               
                   
               
               
                 K18 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 591.5 
                 3.91 
                 SA 
               
               
                   
               
               
                 K19 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 591.5 
                 3.6  
                 SA 
               
               
                   
               
               
                 K20 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 589.4 
                 3.84 
                 SA 
               
               
                   
               
               
                 K21 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 603.4 
                 3.38 
                 SB 
               
               
                   
               
               
                 K22 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 603.4 
                 3.44 
                 SB 
               
               
                   
               
               
                 K23 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 603.4 
                 3.44 
                 SB 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
             
               
                 TABLE 43 
               
               
                   
               
               
                 Ex. 
                   
                 obs MS 
                 tR 
                 Measurement 
               
               
                 No. 
                 —B 
                 [M + 1] 
                 (min) 
                 Method 
               
               
                   
               
             
            
               
                 K25 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 624.4 
                 3.4  
                 SB 
               
               
                   
               
               
                 K26 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 586.3 
                 2.92 
                 SB 
               
               
                   
               
               
                 K27 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 574.3 
                 2.99 
                 SB 
               
               
                   
               
               
                 K28 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 590.5 
                 3.17 
                 SB 
               
               
                   
               
               
                 K29 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 570.6 
                 2.61 
                 SB 
               
               
                   
               
               
                 K30 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 609.3 
                 3.51 
                 SB 
               
               
                   
               
               
                 K31 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 556.3 
                 2.53 
                 SB 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
             
               
                 TABLE 44 
               
               
                   
               
               
                   
                   
                 obs MS 
                   
                 Measurement 
               
               
                 Ex. No. 
                 —B 
                 [M + 1] 
                 tR (min) 
                 Method 
               
               
                   
               
             
            
               
                 L1 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 581.3 
                 3.78 
                 SB 
               
               
                   
               
               
                 L2 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 581.3 
                 3.26 
                 SB 
               
               
                   
               
               
                 L3 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 581.3 
                 3.47 
                 SB 
               
               
                   
               
               
                 L4 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 581.3 
                 4.13 
                 SB 
               
               
                   
               
               
                 L5 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 531.1 
                 2.82 
                 SB 
               
               
                   
               
               
                 L6 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 538.4 
                 3.74 
                 SB 
               
               
                   
               
               
                 L7 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 538.4 
                 3.42 
                 SB 
               
               
                   
               
               
                 L8 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 544.3 
                 2.51 
                 SB 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
             
               
                 TABLE 45 
               
               
                   
               
               
                   
                   
                 obs MS 
                   
                 Measurement 
               
               
                 Ex. No. 
                 —B 
                 [M + 1] 
                 tR (min) 
                 Method 
               
               
                   
               
             
            
               
                 L9 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 514.3 
                 3.05 
                 SB 
               
               
                   
               
            
           
         
       
     
     
       
         
         
             
             
         
       
     
     
       
         
           
               
               
               
               
               
             
               
                 TABLE 46 
               
               
                   
               
               
                   
                   
                 obs MS 
                   
                 Measurement 
               
               
                 Ex. No. 
                 —B 
                 [M + 1] 
                 tR (min) 
                 Method 
               
               
                   
               
             
            
               
                 M1 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 542.5 
                 3.62 
                 SA 
               
               
                   
               
               
                 M2 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 542.3 
                 3.66 
                 SA 
               
               
                   
               
               
                 M3 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 542.5 
                 3.66 
                 SA 
               
               
                   
               
               
                 M4 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 558.5 
                 3.8  
                 SA 
               
               
                   
               
               
                 M5 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 558.6 
                 3.82 
                 SA 
               
               
                   
               
               
                 M6 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 558.6 
                 3.83 
                 SA 
               
               
                   
               
               
                 M7 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 554.6 
                 3.56 
                 SA 
               
               
                   
               
               
                 M8 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 554.6 
                 3.62 
                 SA 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
             
               
                 TABLE 47 
               
               
                   
               
               
                 Ex. 
                   
                 obs MS 
                 tR 
                 Measurement 
               
               
                 No. 
                 —B 
                 [M + 1] 
                 (min) 
                 Method 
               
               
                   
               
             
            
               
                 M9 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 554.6 
                 3.65 
                 SA 
               
               
                   
               
               
                 M10 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 592.5 
                 3.81 
                 SA 
               
               
                   
               
               
                 M11 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 592.3 
                 3.94 
                 SA 
               
               
                   
               
               
                 M12 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 592.3 
                 3.96 
                 SA 
               
               
                   
               
               
                 M13 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 549.6 
                 3.53 
                 SA 
               
               
                   
               
               
                 M14 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 549.6 
                 3.53 
                 SA 
               
               
                   
               
               
                 M15 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 560.6 
                 3.7  
                 SA 
               
               
                   
               
               
                 M16 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 563.7 
                 3.59 
                 SA 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
             
               
                 TABLE 48 
               
               
                   
               
               
                 Ex. 
                   
                 obs MS 
                 tR 
                 Measurement 
               
               
                 No. 
                 —B 
                 [M + 1] 
                 (min) 
                 Method 
               
               
                   
               
             
            
               
                 M17 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 560.5 
                 3.74 
                 SA 
               
               
                   
               
               
                 M18 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 560.6 
                 3.7  
                 SA 
               
               
                   
               
               
                 M19 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 606.2 
                 3.99 
                 SA 
               
               
                   
               
               
                 M20 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 606.5 
                 3.99 
                 SA 
               
               
                   
               
               
                 M21 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 606.3 
                 3.99 
                 SA 
               
               
                   
               
               
                 M22 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 556.7 
                 3.74 
                 SA 
               
               
                   
               
               
                 M23 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 556.5 
                 3.72 
                 SA 
               
               
                   
               
               
                 M24 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 556.4 
                 3.7  
                 SA 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
             
               
                 TABLE 49 
               
               
                   
               
               
                 Ex. 
                   
                 obs MS 
                 tR 
                 Measurement 
               
               
                 No. 
                 —B 
                 [M + 1] 
                 (min) 
                 Method 
               
               
                   
               
             
            
               
                 M25 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 572.5 
                 3.87 
                 SA 
               
               
                   
               
               
                 M26 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 572.5 
                 3.85 
                 SA 
               
               
                   
               
               
                 M27 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 572.5 
                 3.87 
                 SA 
               
               
                   
               
               
                 M28 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 563.7 
                 3.57 
                 SA 
               
               
                   
               
               
                 M29 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 568.6 
                 3.72 
                 SA 
               
               
                   
               
               
                 M30 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 568.6 
                 3.64 
                 SA 
               
               
                   
               
               
                 M31 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 568.7 
                 3.63 
                 SA 
               
               
                   
               
               
                 M32 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 462.3 
                 3.11 
                 SA 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
             
               
                 TABLE 50 
               
               
                   
               
               
                 Ex. 
                   
                 obs MS 
                 tR 
                 Measurement 
               
               
                 No. 
                 —B 
                 [M + 1] 
                 (min) 
                 Method 
               
               
                   
               
             
            
               
                 M33 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 476.3 
                 3.29 
                 SA 
               
               
                   
               
               
                 M34 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 490.6 
                 3.44 
                 SA 
               
               
                   
               
               
                 M35 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 488.6 
                 3.37 
                 SA 
               
               
                   
               
               
                 M36 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 594.5 
                 3.8  
                 SA 
               
               
                   
               
               
                 M37 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 582.3 
                 3.88 
                 SA 
               
               
                   
               
               
                 M38 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 598.7 
                 4.04 
                 SA 
               
               
                   
               
               
                 M39 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 539.7 
                 2.82 
                 SA 
               
               
                   
               
               
                 M40 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 555.6 
                 3.43 
                 SA 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
             
               
                 TABLE 51 
               
               
                   
               
               
                   
                   
                 obs MS 
                   
                 Measurement 
               
               
                 Ex. No. 
                 —B 
                 [M + 1] 
                 tR (min) 
                 Method 
               
               
                   
               
             
            
               
                 M41 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 593.6 
                 3.7  
                 SA 
               
               
                   
               
               
                 M42 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 559.5 
                 3.56 
                 SA 
               
               
                   
               
               
                 M43 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 593.5 
                 3.71 
                 SA 
               
               
                   
               
               
                 M44 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 564.5 
                 3.94 
                 SA 
               
               
                   
               
               
                 M45 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 530.5 
                 3.51 
                 SA 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
             
               
                 TABLE 52 
               
               
                   
               
               
                   
                   
                 obs MS 
                   
                 Measurement 
               
               
                 Ex. No. 
                 —B 
                 [M + 1] 
                 tR (min) 
                 Method 
               
               
                   
               
             
            
               
                 N1 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 594.5 
                 4.04 
                 SA 
               
               
                   
               
               
                 N2 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 594.4 
                 4.16 
                 SA 
               
               
                   
               
               
                 N3 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 594.4 
                 4.16 
                 SA 
               
               
                   
               
               
                 N4 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 578.3 
                 3.93 
                 SA 
               
               
                   
               
               
                 N5 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 578.5 
                 4.01 
                 SA 
               
               
                   
               
               
                 N6 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 578.5 
                 3.97 
                 SA 
               
               
                   
               
               
                 N7 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 590.4 
                 3.71 
                 SA 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
             
               
                 TABLE 53 
               
               
                   
               
               
                 Ex.  
                   
                 obs MS 
                   
                 Measurement 
               
               
                 No. 
                 —B 
                 [M + 1] 
                 tR (min) 
                 Method 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
               
            
               
                 N9  
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 590.5 
                 3.84 
                 SA 
               
               
                   
               
               
                 N10 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 628.5 
                 4.13 
                 SA 
               
               
                   
               
               
                 N11 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 628.6 
                 4.24 
                 SA 
               
               
                   
               
               
                 N12 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 628.5 
                 4.26 
                 SA 
               
               
                   
               
               
                 N13 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 585.6 
                 3.81 
                 SA 
               
               
                   
               
               
                 N14 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 585.4 
                 3.86 
                 SA 
               
               
                   
               
               
                 N15 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 585.4 
                 3.9 
                 SA 
               
               
                   
               
               
                 N16 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 596.3 
                 4.02 
                 SA 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
             
               
                 TABLE 54 
               
               
                   
               
               
                 Ex.  
                   
                 obs MS 
                   
                 Measurement 
               
               
                 No. 
                 —B 
                 [M + 1] 
                 tR (min) 
                 Method 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
               
            
               
                 N17 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 596.4 
                 4.12 
                 SA 
               
               
                   
               
               
                 N18 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 596.4 
                 4.03 
                 SA 
               
               
                   
               
               
                 N19 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 596.4 
                 4.11 
                 SA 
               
               
                   
               
               
                 N20 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 596.4 
                 3.93 
                 SA 
               
               
                   
               
               
                 N21 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 592.3 
                 3.93 
                 SA 
               
               
                   
               
               
                 N22 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 608.5 
                 4.09 
                 SA 
               
               
                   
               
               
                 N23 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 566.4 
                 3.8 
                 SA 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
             
               
                 TABLE 55 
               
               
                   
               
               
                 Ex.  
                   
                 obs MS 
                   
                 Measurement 
               
               
                 No. 
                 —B 
                 [M + 1] 
                 tR (min) 
                 Method 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
               
            
               
                 O1 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 557.7 
                 3.8 
                 SB 
               
               
                   
               
               
                 O2 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 557.7 
                 3.92 
                 SB 
               
               
                   
               
               
                 O3 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 557.4 
                 3.88 
                 SB 
               
               
                   
               
               
                 O4 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 573.7 
                 3.97 
                 SB 
               
               
                   
               
               
                 O5 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 573.7 
                 4.03 
                 SB 
               
               
                   
               
               
                 O6 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 573.7 
                 4.03 
                 SB 
               
               
                   
               
               
                 O7 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 569.8 
                 3.9 
                 SB 
               
               
                   
               
               
                 O8 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 569.8 
                 3.78 
                 SB 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
             
               
                 TABLE 56 
               
               
                   
               
               
                   
                   
                   
                   
                 Measure- 
               
               
                 Ex.  
                   
                 obs MS 
                   
                 ment 
               
               
                 No. 
                 —B 
                 [M + 1] 
                 tR (min) 
                 Method 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
               
            
               
                 O9  
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 569.8 
                 3.74 
                 SB 
               
               
                   
               
               
                 O10 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 564.7 
                 3.67 
                 SB 
               
               
                   
               
               
                 O11 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 564.7 
                 3.8 
                 SB 
               
               
                   
               
               
                 O12 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 564.7 
                 3.8 
                 SB 
               
               
                   
               
               
                 O13 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 575.7 
                 3.82 
                 SB 
               
               
                   
               
               
                 O14 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 575.7 
                 3.95 
                 SB 
               
               
                   
               
               
                 O15 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 575.7  
                 3.69 
                 SB 
               
               
                   
               
               
                 O16 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 575.7  
                 3.99 
                 SB 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
             
               
                 TABLE 57 
               
               
                   
               
               
                   
                   
                   
                   
                 Measure- 
               
               
                 Ex. 
                   
                 obs MS 
                 tR  
                 ment 
               
               
                 No. 
                 —B 
                 [M + 1] 
                 (min) 
                 Method 
               
               
                   
               
             
            
               
                 O17 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 575.7 
                 4.05 
                 SB 
               
               
                   
               
               
                 O18 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 587.4 
                 3.32 
                 SB 
               
               
                   
               
               
                 O19 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 587.4 
                 3.4  
                 SB 
               
               
                   
               
               
                 O20 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 587.4 
                 3.36 
                 SB 
               
               
                   
               
               
                 O21 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 557.4 
                 3.34 
                 SB 
               
               
                   
               
               
                 O22 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 593.6 
                 3.38 
                 SB 
               
               
                   
               
               
                 O23 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 540.4 
                 2.48 
                 SB 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
             
               
                 TABLE 58 
               
               
                   
               
               
                   
                   
                 obs MS 
                   
                 Measurement 
               
               
                 Ex. No. 
                 —B 
                 [M + 1] 
                 tR (min) 
                 Method 
               
               
                   
               
             
            
               
                 P1 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 565.6 
                 3.67 
                 SB 
               
               
                   
               
               
                 P2 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 565.6 
                 3.15 
                 SB 
               
               
                   
               
               
                 P3 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 565.6 
                 3.36 
                 SB 
               
               
                   
               
               
                 P4 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 565.6 
                 4.07 
                 SB 
               
               
                   
               
               
                 P5 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 515.4 
                 2.71 
                 SB 
               
               
                   
               
               
                 P6 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 522.2 
                 3.63 
                 SB 
               
               
                   
               
               
                 P7 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 522.2 
                 3.40 
                 SB 
               
               
                   
               
               
                 P8 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 528.3 
                 2.44 
                 SB 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
             
               
                 TABLE 59 
               
               
                   
               
               
                   
                   
                 obs MS 
                   
                 Measurement 
               
               
                 Ex. No. 
                 —B 
                 [M + 1] 
                 tR (min) 
                 Method 
               
               
                   
               
             
            
               
                 P9  
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 498.3 
                 2.94 
                 SB 
               
               
                   
               
               
                 P10 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 522.4 
                 3.36 
                 SB 
               
               
                   
               
            
           
         
       
     
     
       
         
         
             
             
         
       
     
     
       
         
           
               
               
               
               
               
             
               
                 TABLE 60 
               
               
                   
               
               
                   
                   
                 obs MS 
                   
                 Measurement 
               
               
                 Ex. No. 
                 —B 
                 [M + 1] 
                 tR (min) 
                 Method 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
               
            
               
                 Q1 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 572.6 
                 3.87 
                 SA 
               
               
                   
               
               
                 Q2 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 588.6 
                 4.11 
                 SA 
               
               
                   
               
               
                 Q3 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 584.5 
                 3.8 
                 SA 
               
               
                   
               
               
                 Q4 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 572.6 
                 3.9 
                 SA 
               
               
                   
               
               
                 Q5 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 588.6 
                 4.07 
                 SA 
               
               
                   
               
               
                 Q6 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 584.5 
                 3.85 
                 SA 
               
               
                   
               
               
                 Q7 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 572.5 
                 3.88 
                 SA 
               
               
                   
               
               
                 Q8 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 588.6 
                 4.06 
                 SA 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
             
               
                 TABLE 61 
               
               
                   
               
               
                   
                   
                   
                   
                 Measure- 
               
               
                 Ex. 
                   
                 obs MS 
                   
                 ment 
               
               
                 No. 
                 —B 
                 [M + 1] 
                 tR (min) 
                 Method 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
               
            
               
                 Q9  
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 584.5 
                 3.82 
                 SA 
               
               
                   
               
               
                 Q10 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 602.6 
                 4.08 
                 SA 
               
               
                   
               
               
                 Q11 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 598.6 
                 3.83 
                 SA 
               
               
                   
               
               
                 Q12 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 586.6 
                 3.91 
                 SA 
               
               
                   
               
               
                 Q13 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 598.7 
                 3.84 
                 SA 
               
               
                   
               
               
                 Q14 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 555.5 
                 3.35 
                 SA 
               
               
                   
               
               
                 Q15 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 555.5 
                 3.06 
                 SA 
               
               
                   
               
               
                 Q16 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 555.5 
                 3 
                 SA 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
             
               
                 TABLE 62 
               
               
                   
               
               
                   
                   
                 obs MS 
                   
                 Measurement 
               
               
                 Ex. No. 
                 —B 
                 [M + 1] 
                 tR (min) 
                 Method 
               
               
                   
               
             
            
               
                 Q17 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 492.7 
                 3.34 
                 SA 
               
               
                   
               
               
                 Q18 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 506.7 
                 3.52 
                 SA 
               
               
                   
               
               
                 Q19 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 520.7 
                 3.68 
                 SA 
               
               
                   
               
               
                 Q20 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 518.7 
                 3.61 
                 SA 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
             
               
                 TABLE 63 
               
               
                   
               
               
                   
                   
                 obs MS 
                   
                 Measurement 
               
               
                 Ex. No. 
                 —B 
                 [M + 1] 
                 tR (min) 
                 Method 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
               
            
               
                 R1 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 608.3 
                 4.17 
                 SA 
               
               
                   
               
               
                 R2 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 620.4 
                 4.04 
                 SA 
               
               
                   
               
               
                 R3 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 608.4 
                 4.23 
                 SA 
               
               
                   
               
               
                 R4 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 624.4 
                 4.4 
                 SA 
               
               
                   
               
               
                 R5 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 620.5 
                 4.19 
                 SA 
               
               
                   
               
               
                 R6 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 608.3 
                 4.21 
                 SA 
               
               
                   
               
               
                 R7 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 624.5 
                 4.41 
                 SA 
               
               
                   
               
               
                 R8 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 622.6 
                 4.15 
                 SA 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
             
               
                 TABLE 64 
               
               
                   
               
               
                 Ex.  
                   
                 obs MS 
                   
                 Measurement 
               
               
                 No. 
                 —B 
                 [M + 1] 
                 tR (min) 
                 Method 
               
               
                   
               
             
            
               
                 R9  
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 638.4 
                 4.31 
                 SA 
               
               
                   
               
               
                 R10 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 591.4 
                 3.72 
                 SA 
               
               
                   
               
               
                 R11 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 528.6 
                 3.61 
                 SA 
               
               
                   
               
               
                 R12 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 542.5 
                 3.74 
                 SA 
               
               
                   
               
               
                 R13 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 556.5 
                 3.94 
                 SA 
               
               
                   
               
               
                 R14 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 554.4 
                 3.77 
                 SA 
               
               
                   
               
               
                 R15 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 624.4 
                 4.29 
                 SA 
               
               
                   
               
               
                 R16 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 620.5 
                 4.15 
                 SA 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
               
             
               
                 TABLE 65 
               
               
                   
               
               
                   
                   
                   
                 obs MS 
                   
                 Measurement 
               
               
                   
                 Ex. No. 
                 —B 
                 [M + 1] 
                 tR (min) 
                 Method 
               
               
                   
               
             
            
               
                   
                 R17 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 556.5 
                 3.83 
                 SA 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
             
               
                 TABLE 66 
               
               
                   
               
               
                   
                   
                 obs MS 
                   
                 Measurement 
               
               
                 Ex. No. 
                 —B 
                 [M + 1] 
                 tR (min) 
                 Method 
               
               
                   
               
             
            
               
                 S1 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 552.4 
                 3.74 
                 SB 
               
               
                   
               
               
                 S2 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 595.5 
                 3.97 
                 SB 
               
               
                   
               
               
                 S3 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 595.5 
                 3.69 
                 SB 
               
               
                   
               
               
                 S4 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 545.4 
                 2.90 
                 SB 
               
               
                   
               
               
                 S5 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 552.4 
                 3.34 
                 SB 
               
               
                   
               
               
                 S6 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 552.4 
                 3.57 
                 SB 
               
               
                   
               
               
                 S7 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 558.3 
                 2.61 
                 SB 
               
               
                   
               
            
           
         
       
     
     
       
         
         
             
             
         
       
     
     
       
         
           
               
               
               
               
               
             
               
                 TABLE 67 
               
               
                   
               
               
                 Ex.  
                   
                 obs MS 
                   
                 Measurement 
               
               
                 No. 
                 —B 
                 [M + 1] 
                 tR (min) 
                 Method 
               
               
                   
               
             
            
               
                 U1 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 530.5 
                 3.43 
                 SA 
               
               
                   
               
               
                 U2 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 546.5 
                 3.56 
                 SA 
               
               
                   
               
               
                 U3 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 542.5 
                 3.39 
                 SA 
               
               
                   
               
               
                 U4 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 580.4 
                 3.72 
                 SA 
               
               
                   
               
               
                 U5 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 537.6 
                 3.31 
                 SA 
               
               
                   
               
               
                 U6 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 530.5 
                 3.41 
                 SA 
               
               
                   
               
               
                 U7 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 546.6 
                 3.58 
                 SA 
               
               
                   
               
               
                 U8 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 542.6 
                 3.37 
                 SA 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
             
               
                 TABLE 68 
               
               
                   
               
               
                 Ex. 
                   
                 obs MS 
                 tR 
                 Measurement 
               
               
                 No. 
                 —B 
                 [M + 1] 
                 (min) 
                 Method 
               
               
                   
               
             
            
               
                 U9 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 580.4 
                 3.73 
                 SA 
               
               
                   
               
               
                 U10 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 537.6 
                 3.31 
                 SA 
               
               
                   
               
               
                 U11 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 560.6 
                 3.64 
                 SA 
               
               
                   
               
               
                 U12 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 556.7 
                 3.46 
                 SA 
               
               
                   
               
               
                 U13 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 594.5 
                 3.82 
                 SA 
               
               
                   
               
               
                 U14 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 544.6 
                 3.48 
                 SA 
               
               
                   
               
               
                 U15 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 556.7 
                 3.46 
                 SA 
               
               
                   
               
               
                 U16 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 540.6 
                 3.6  
                 SA 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
             
               
                 TABLE 69 
               
               
                   
               
               
                   
                   
                 obs MS 
                   
                 Measurement 
               
               
                 Ex. No. 
                 —B 
                 [M + 1] 
                 tR (min) 
                 Method 
               
               
                   
               
             
            
               
                 U17 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 513.7 
                 3.07 
                 SA 
               
               
                   
               
               
                 U18 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 513.7 
                 2.73 
                 SA 
               
               
                   
               
               
                 U19 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 513.7 
                 2.68 
                 SA 
               
               
                   
               
               
                 U20 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 518.6 
                 3.35 
                 SA 
               
               
                   
               
               
                 U21 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 450.5 
                 2.92 
                 SA 
               
               
                   
               
               
                 U22 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 464.5 
                 3.08 
                 SA 
               
               
                   
               
               
                 U23 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 478.5 
                 3.21 
                 SA 
               
               
                   
               
               
                 U24 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 476.3 
                 3.16 
                 SA 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
             
               
                 TABLE 70 
               
               
                   
               
               
                 Ex. 
                   
                 obs MS 
                 tR 
                 Measurement 
               
               
                 No. 
                 —B 
                 [M + 1] 
                 (min) 
                 Method 
               
               
                   
               
             
            
               
                 U25 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 518.6 
                 3.3  
                 SA 
               
               
                   
               
               
                 U26 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 530.5 
                 3.42 
                 SA 
               
               
                   
               
               
                 U27 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 582.5 
                 3.62 
                 SA 
               
               
                   
               
               
                 U28 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 570.6 
                 3.68 
                 SA 
               
               
                   
               
               
                 U29 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 586.5 
                 3.91 
                 SA 
               
               
                   
               
               
                 U30 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 527.7 
                 2.7  
                 SA 
               
               
                   
               
               
                 U31 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 543.7 
                 3.24 
                 SA 
               
               
                   
               
               
                 U32 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 581.5 
                 3.51 
                 SA 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
             
               
                 TABLE 71 
               
               
                   
               
               
                   
                   
                 obs MS 
                   
                 Measurement 
               
               
                 Ex. No. 
                 —B 
                 [M + 1] 
                 tR (min) 
                 Method 
               
               
                   
               
             
            
               
                 U33 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 547.7 
                 3.49 
                 SA 
               
               
                   
               
               
                 U34 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 581.5 
                 3.65 
                 SA 
               
               
                   
               
               
                 U35 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 552.4 
                 3.73 
                 SA 
               
               
                   
               
               
                 U36 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 518.7 
                 3.33 
                 SA 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
             
               
                 TABLE 72 
               
               
                   
               
               
                   
                   
                 obs MS 
                   
                 Measurement 
               
               
                 Ex. No. 
                 —B 
                 [M + 1] 
                 tR (min) 
                 Method 
               
               
                   
               
             
            
               
                 V1 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 566.4 
                 3.72 
                 SA 
               
               
                   
               
               
                 V2 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 582.3 
                 3.85 
                 SA 
               
               
                   
               
               
                 V3 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 578.4 
                 3.61 
                 SA 
               
               
                   
               
               
                 V4 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 573.6 
                 3.62 
                 SA 
               
               
                   
               
               
                 V5 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 566.5 
                 3.78 
                 SA 
               
               
                   
               
               
                 V6 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 582.1 
                 3.92 
                 SA 
               
               
                   
               
               
                 V7 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 578.5 
                 3.74 
                 SA 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
             
               
                 TABLE 73 
               
               
                   
               
               
                 Ex. 
                   
                 obs MS 
                 tR 
                 Measurement 
               
               
                 No. 
                 —B 
                 [M + 1] 
                 (min) 
                 Method 
               
               
                   
               
             
            
               
                 V9 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 566.4 
                 3.76 
                 SA 
               
               
                   
               
               
                 V10 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 582.3 
                 3.94 
                 SA 
               
               
                   
               
               
                 V11 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 578.5 
                 3.7  
                 SA 
               
               
                   
               
               
                 V12 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 573.5 
                 3.68 
                 SA 
               
               
                   
               
               
                 V13 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 580.4 
                 3.66 
                 SA 
               
               
                   
               
               
                 V14 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 596.3 
                 3.9  
                 SA 
               
               
                   
               
               
                 V15 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 549.5 
                 3.31 
                 SA 
               
               
                   
               
               
                 V16 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 486.5 
                 3.13 
                 SA 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
             
               
                 TABLE 74 
               
               
                   
               
               
                   
                   
                 obs MS 
                   
                 Measurement 
               
               
                 Ex. No. 
                 —B 
                 [M + 1] 
                 tR (min) 
                 Method 
               
               
                   
               
             
            
               
                 V17 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 514.5 
                 3.45 
                 SA 
               
               
                   
               
               
                 V18 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 554.5 
                 3.64 
                 SA 
               
               
                   
               
               
                 V19 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 512.4 
                 3.33 
                 SA 
               
               
                   
               
               
                 V20 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 514.5 
                 3.41 
                 SA 
               
               
                   
               
               
                 V21 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 584.4 
                 3.89 
                 SA 
               
               
                   
               
               
                 V22 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 584.4 
                 3.87 
                 SA 
               
               
                   
               
               
                 V23 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 584.4 
                 3.72 
                 SA 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
             
               
                 TABLE 75 
               
               
                   
               
               
                 Ex. 
                   
                 obs MS 
                 tR 
                 Measurement 
               
               
                 No. 
                 —B 
                 [M + 1] 
                 (min) 
                 Method 
               
               
                   
               
             
            
               
                 W1 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 561.7 
                 3.84 
                 SB 
               
               
                   
               
               
                 W2 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 561.7 
                 3.9  
                 SB 
               
               
                   
               
               
                 W3 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 561.7 
                 3.86 
                 SB 
               
               
                   
               
               
                 W4 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 545.7 
                 3.65 
                 SB 
               
               
                   
               
               
                 W5 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 545.7 
                 3.76 
                 SB 
               
               
                   
               
               
                 W6 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 545.4 
                 3.18 
                 SB 
               
               
                   
               
               
                 W7 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 557.4 
                 3.17 
                 SB 
               
               
                   
               
               
                 W8 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 557.4 
                 3.07 
                 SB 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
             
               
                 TABLE 76 
               
               
                   
               
               
                 Ex. 
                   
                 obs MS 
                 tR 
                 Measurement 
               
               
                 No. 
                 —B 
                 [M + 1] 
                 (min) 
                 Method 
               
               
                   
               
             
            
               
                 W9 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 557.4 
                 3.01 
                 SB 
               
               
                   
               
               
                 W10 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 563.3 
                 3.11 
                 SB 
               
               
                   
               
               
                 W11 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 563.3 
                 3.26 
                 SB 
               
               
                   
               
               
                 W12 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 563.3 
                 3.19 
                 SB 
               
               
                   
               
               
                 W13 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 563.3 
                 2.96 
                 SB 
               
               
                   
               
               
                 W14 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 552.1 
                 2.96 
                 SB 
               
               
                   
               
               
                 W15 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 552.1 
                 3.19 
                 SB 
               
               
                   
               
               
                 W16 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 552.1 
                 3.11 
                 SB 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
             
               
                 TABLE 77 
               
               
                   
               
               
                   
                   
                   
                   
                 Measure- 
               
               
                 Ex. 
                   
                 obs MS 
                 tR 
                 ment 
               
               
                 No. 
                 —B 
                 [M + 1] 
                 (min) 
                 Method 
               
               
                   
               
             
            
               
                 W17 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 559.4 
                 3.09 
                 SB 
               
               
                   
               
               
                 W18 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 559.4 
                 3.07 
                 SB 
               
               
                   
               
               
                 W19 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 559.4 
                 3.15 
                 SB 
               
               
                   
               
               
                 W20 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 575.4 
                 3.18 
                 SB 
               
               
                   
               
               
                 W21 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 575.4 
                 3.26 
                 SB 
               
               
                   
               
               
                 W22 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 575.4 
                 3.24 
                 SB 
               
               
                   
               
               
                 W23 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 555.2 
                 3.17 
                 SB 
               
               
                   
               
               
                 W24 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 555.2 
                 3.19 
                 SB 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
             
               
                 TABLE 78 
               
               
                   
               
               
                   
                   
                   
                   
                 Mea- 
               
               
                   
                   
                   
                   
                 sure- 
               
               
                 Ex. 
                   
                 obs MS 
                 tR 
                 ment 
               
               
                 No. 
                 —B 
                 [M + 1] 
                 (min) 
                 Method 
               
               
                   
               
             
            
               
                 W25 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 571.5 
                 3.11 
                 SB 
               
               
                   
               
               
                 W26 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 571.5 
                 3.07 
                 SB 
               
               
                   
               
               
                 W27 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 571.5 
                 3.03 
                 SB 
               
               
                   
               
               
                 W28 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 542.3 
                 2.38 
                 SB 
               
               
                   
               
               
                 W29 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 596.4 
                 3.17 
                 SB 
               
               
                   
               
               
                 W30 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 558.3 
                 2.69 
                 SB 
               
               
                   
               
               
                 W31 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 546.2 
                 2.8  
                 SB 
               
               
                   
               
               
                 W32 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 562.2 
                 2.99 
                 SB 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
             
               
                 TABLE 79 
               
               
                   
               
               
                   
                   
                 obs MS 
                   
                 Measurement 
               
               
                 Ex. No. 
                 —B 
                 [M + 1] 
                 tR (min) 
                 Method 
               
               
                   
               
             
            
               
                 W33 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 563.3 
                 3.34 
                 SB 
               
               
                   
               
               
                 W34 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 581.3 
                 3.24 
                 SB 
               
               
                   
               
               
                 W35 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 555.2 
                 3.13 
                 SB 
               
               
                   
               
               
                 W37 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 528.3 
                 2.38 
                 SB 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
             
               
                 TABLE 80 
               
               
                   
               
               
                   
                   
                 obs MS 
                   
                 Measurement 
               
               
                 Ex. No. 
                 —B 
                 [M + 1] 
                 tR (min) 
                 Method 
               
               
                   
               
             
            
               
                 X1 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 553.2 
                 3.63 
                 SB 
               
               
                   
               
               
                 X2 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 553.2 
                 2.84 
                 SB 
               
               
                   
               
               
                 X3 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 553.2 
                 2.99 
                 SB 
               
               
                   
               
               
                 X4 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 553.2 
                 3.86 
                 SB 
               
               
                   
               
               
                 X5 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 503.4 
                 2.44 
                 SB 
               
               
                   
               
               
                 X6 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 510.4 
                 3.42 
                 SB 
               
               
                   
               
               
                 X7 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 510.4 
                 2.78 
                 SB 
               
               
                   
               
               
                 X8 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 510.4 
                 3.19 
                 SB 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
             
               
                 TABLE 81 
               
               
                   
               
               
                   
                   
                 obs MS 
                   
                 Measurement 
               
               
                 Ex. No. 
                 —B 
                 [M + 1] 
                 tR (min) 
                 Method 
               
               
                   
               
             
            
               
                 X9 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 516.6 
                 2.34 
                 SB 
               
               
                   
               
               
                 X10 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 486.6 
                 2.71 
                 SB 
               
               
                   
               
               
                 X11 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 510.4 
                 3.05 
                 SB 
               
               
                   
               
            
           
         
       
     
     
       
         
         
             
             
         
       
     
     
       
         
           
               
               
               
               
               
             
               
                 TABLE 82 
               
               
                   
               
               
                   
                   
                 obs MS 
                   
                 Measurement 
               
               
                 Ex. No. 
                 —B 
                 [M + 1] 
                 tR (min) 
                 Method 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
               
            
               
                 Y1 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 530.5 
                 3.4 
                 SA 
               
               
                   
               
               
                 Y2 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 530.5 
                 3.42 
                 SA 
               
               
                   
               
               
                 Y3 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 546.6 
                 3.58 
                 SA 
               
               
                   
               
               
                 Y4 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 542.5 
                 3.38 
                 SA 
               
               
                   
               
               
                 Y5 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 537.5 
                 3.31 
                 SA 
               
               
                   
               
               
                 Y6 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 530.5 
                 3.41 
                 SA 
               
               
                   
               
               
                 Y7 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 546.7 
                 3.58 
                 SA 
               
               
                   
               
               
                 Y8 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 580.4 
                 3.72 
                 SA 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
             
               
                 TABLE 83 
               
               
                   
               
               
                   
                   
                 obs 
                   
                 Measure- 
               
               
                 Ex. 
                   
                 MS 
                 tR  
                 ment 
               
               
                 No. 
                 —B 
                 [M + 1]  
                 (min) 
                 Method 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
               
            
               
                 Y9 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 537.5 
                 3.32 
                 SA 
               
               
                   
               
               
                 Y10 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 560.7 
                 3.67 
                 SA 
               
               
                   
               
               
                 Y11 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 556.4 
                 3.45 
                 SA 
               
               
                   
               
               
                 Y12 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 580.4 
                 3.7 
                 SA 
               
               
                   
               
               
                 Y13 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 542.6 
                 3.37 
                 SA 
               
               
                   
               
               
                 Y14 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 556.5 
                 3.47 
                 SA 
               
               
                   
               
               
                 Y15 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 594.5 
                 3.82 
                 SA 
               
               
                   
               
               
                 Y16 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 544.6 
                 3.5 
                 SA 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
             
               
                 TABLE 84 
               
               
                   
               
               
                   
                   
                 obs 
                   
                 Measure- 
               
               
                 Ex. 
                   
                 MS 
                 tR  
                 ment 
               
               
                 No. 
                 —B 
                 [M + 1]  
                 (min) 
                 Method 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
               
            
               
                 Y17 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 476.5 
                 3.16 
                 SA 
               
               
                   
               
               
                 Y18 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 582.5 
                 3.6 
                 SA 
               
               
                   
               
               
                 Y19 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 549.6 
                 3.49 
                 SA 
               
               
                   
               
               
                 Y20 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 548.5 
                 3.53 
                 SA 
               
               
                   
               
               
                 Y21 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 548.6 
                 3.54 
                 SA 
               
               
                   
               
               
                 Y22 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 594.4 
                 3.78 
                 SA 
               
               
                   
               
               
                 Y23 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 594.4 
                 3.82 
                 SA 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
             
               
                 TABLE 85 
               
               
                   
               
               
                   
                   
                 obs 
                   
                 Measure- 
               
               
                 Ex. 
                   
                 MS 
                 tR  
                 ment 
               
               
                 No. 
                 —B 
                 [M + 1]  
                 (min) 
                 Method 
               
               
                   
               
             
            
               
                 Y25 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 544.5 
                 3.59 
                 SA 
               
               
                   
               
               
                 Y26 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 560.6 
                 3.64 
                 SA 
               
               
                   
               
               
                 Y27 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 560.6 
                 3.67 
                 SA 
               
               
                   
               
               
                 Y28 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 551.7 
                 3.39 
                 SA 
               
               
                   
               
               
                 Y29 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 551.5 
                 3.38 
                 SA 
               
               
                   
               
               
                 Y30 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 556.5 
                 3.52 
                 SA 
               
               
                   
               
               
                 Y31 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 570.4 
                 3.64 
                 SA 
               
               
                   
               
               
                 Y32 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 527.7 
                 2.69 
                 SA 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
             
               
                 TABLE 86 
               
               
                   
               
               
                   
                   
                 obs 
                   
                 Measure- 
               
               
                 Ex. 
                   
                 MS 
                 tR  
                 ment 
               
               
                 No. 
                 —B 
                 [M + 1]  
                 (min) 
                 Method 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
               
            
               
                 Y33 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 543.6 
                 3.2 
                 SA 
               
               
                   
               
               
                 Y34 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 581.5 
                 3.48 
                   
               
               
                   
               
               
                 Y35 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 547.6 
                 3.45 
                   
               
               
                   
               
               
                 Y36 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 581.5 
                 3.64 
                   
               
               
                   
               
               
                 Y37 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 552.4 
                 3.72 
                   
               
               
                   
               
               
                 Y38 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 518.6 
                 3.32 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
               
             
               
                   
                 TABLE 87 
               
               
                   
                   
               
               
                   
                   
                   
                 obs 
                   
                 Measure- 
               
               
                   
                 Ex. 
                   
                 MS 
                 tR  
                 ment 
               
               
                   
                 No. 
                 —B 
                 [M + 1]  
                 (min) 
                 Method 
               
               
                   
                   
               
             
            
               
                   
                 Z1 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 566.5 
                 3.72 
                 SA 
               
               
                   
                   
               
               
                   
                 Z2 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 582.3 
                 3.85 
                 SA 
               
               
                   
                   
               
               
                   
                 Z3 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 578.3 
                 3.62 
                 SA 
               
               
                   
                   
               
               
                   
                 Z4 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 573.5 
                 3.63 
                 SA 
               
               
                   
                   
               
               
                   
                 Z5 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 566.5 
                 3.79 
                 SA 
               
               
                   
                   
               
               
                   
                 Z6 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 582.4 
                 3.93 
                 SA 
               
               
                   
                   
               
               
                   
                 Z7 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 578.5 
                 3.76 
                 SA 
               
               
                   
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
             
               
                 TABLE 88 
               
               
                   
               
               
                   
                   
                 obs 
                   
                 Measure- 
               
               
                 Ex. 
                   
                 MS 
                 tR  
                 ment 
               
               
                 No. 
                 —B 
                 [M + 1]  
                 (min) 
                 Method 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
               
            
               
                 Z9 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 566.4 
                 3.76 
                 SA 
               
               
                   
               
               
                 Z10 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 582.3 
                 3.94 
                 SA 
               
               
                   
               
               
                 Z11 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 578.5 
                 3.7 
                 SA 
               
               
                   
               
               
                 Z12 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 573.6 
                 3.69 
                 SA 
               
               
                   
               
               
                 Z13 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 580.4 
                 3.75 
                 SA 
               
               
                   
               
               
                 Z14 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 596.4 
                 3.9 
                 SA 
               
               
                   
               
               
                 Z15 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 549.5 
                 3.3 
                 SA 
               
               
                   
               
               
                 Z16 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 486.5 
                 3.13 
                 SA 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
             
               
                 TABLE 89 
               
               
                   
               
               
                   
                   
                 obs 
                   
                 Measure- 
               
               
                 Ex. 
                   
                 MS 
                 tR  
                 ment 
               
               
                 No. 
                 —B 
                 [M + 1]  
                 (min) 
                 Method 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
               
            
               
                 Z17 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 500.5 
                 3.27 
                 SA 
               
               
                   
               
               
                 Z18 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 514.5 
                 3.46 
                 SA 
               
               
                   
               
               
                 Z19 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 554.5 
                 3.64 
                 SA 
               
               
                   
               
               
                 Z20 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 512.5 
                 3.34 
                 SA 
               
               
                   
               
               
                 Z21 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 514.5 
                 3.43 
                 SA 
               
               
                   
               
               
                 Z22 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 584.4 
                 3.9 
                 SA 
               
               
                   
               
               
                 Z23 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 584.4 
                 3.88 
                 SA 
               
               
                   
               
               
                 Z24 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 584.4 
                 3.71 
                 SA 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
             
               
                 TABLE 90 
               
               
                   
               
               
                   
                   
                 obs 
                   
                 Measure- 
               
               
                 Ex. 
                   
                 MS 
                 tR  
                 ment 
               
               
                 No. 
                 —B 
                 [M + 1]  
                 (min) 
                 Method 
               
               
                   
               
             
            
               
                 Z25 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 584.4 
                 3.82 
                 SA 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
             
               
                 TABLE 91 
               
               
                   
               
               
                   
                   
                 obs 
                   
                 Measure- 
               
               
                 Ex. 
                   
                 MS 
                 tR  
                 ment 
               
               
                 No. 
                 —B 
                 [M + 1]  
                 (min) 
                 Method 
               
               
                   
               
             
            
               
                 AA1 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 561.6 
                 3.74 
                 SA 
               
               
                   
               
               
                 AA2 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 557.2 
                 3.17 
                 SB 
               
               
                   
               
               
                 AA3 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 552.1 
                 2.96 
                 SB 
               
               
                   
               
               
                 AA4 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 552.1 
                 3.09 
                 SB 
               
               
                   
               
               
                 AA5 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 552.1 
                 3.09 
                 SB 
               
               
                   
               
               
                 AA6 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 563.6 
                 3.51 
                 SA 
               
               
                   
               
               
                 AA7 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 563.3 
                 3.32 
                 SB 
               
               
                   
               
               
                 AA8 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 563.3 
                 2.96 
                 SB 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
             
               
                 TABLE 92 
               
               
                   
               
               
                   
                   
                 obs 
                   
                 Measure- 
               
               
                 Ex. 
                   
                 MS 
                 tR  
                 ment 
               
               
                 No. 
                 —B 
                 [M + 1]  
                 (min) 
                 Method 
               
               
                   
               
             
            
               
                 AA9 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 563.6 
                 3.77 
                 SA 
               
               
                   
               
               
                 AA10 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 563.3 
                 3.26 
                 SB 
               
               
                   
               
               
                 AA11 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 555.2 
                 3.17 
                 SB 
               
               
                   
               
               
                 AA12 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 559.4 
                 3.09 
                 SB 
               
               
                   
               
               
                 AA13 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 575.4 
                 3.21 
                 SB 
               
               
                   
               
               
                 AA14 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 571.5 
                 3.09 
                 SB 
               
               
                   
               
               
                 AA15 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 571.5 
                 3.09 
                 SB 
               
               
                   
               
               
                 AA16 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 559.4 
                 3.09 
                 SB 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
             
               
                 TABLE 93 
               
               
                   
               
               
                   
                   
                 obs 
                   
                 Measure- 
               
               
                 Ex. 
                   
                 MS 
                 tR  
                 ment 
               
               
                 No. 
                 —B 
                 [M + 1]  
                 (min) 
                 Method 
               
               
                   
               
             
            
               
                 AA17 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 575.4 
                 3.17 
                 SB 
               
               
                   
               
               
                 AA18 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 575.4 
                 3.21 
                 SB 
               
               
                   
               
               
                 AA19 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 571.5 
                 3.03 
                 SB 
               
               
                   
               
               
                 AA20 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 542.3 
                 2.36 
                 SB 
               
               
                   
               
               
                 AA21 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 596.4 
                 3.17 
                 SB 
               
               
                   
               
               
                 AA22 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 558.3 
                 2.71 
                 SB 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
             
               
                 TABLE 94 
               
               
                   
               
               
                   
                   
                 obs 
                   
                 Measure- 
               
               
                 Ex. 
                   
                 MS 
                 tR  
                 ment 
               
               
                 No. 
                 —B 
                 [M + 1]  
                 (min) 
                 Method 
               
               
                   
               
             
            
               
                 AB1 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 553.2 
                 3.59 
                 SB 
               
               
                   
               
               
                 AB2 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 553.2 
                 2.86 
                 SB 
               
               
                   
               
               
                 AB3 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 553.2 
                 2.99 
                 SB 
               
               
                   
               
               
                 AB4 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 553.2 
                 3.84 
                 SB 
               
               
                   
               
               
                 AB5 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 503.4 
                 2.44 
                 SB 
               
               
                   
               
               
                 AB6 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 516.3 
                 2.34 
                 SB 
               
               
                   
               
               
                 AB7 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 486.3 
                 2.69 
                 SB 
               
               
                   
               
               
                 AB8 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 510.4 
                 3.05 
                 SB 
               
               
                   
               
            
           
         
       
     
     
       
         
         
             
             
         
       
     
     
       
         
           
               
               
               
               
               
             
               
                 TABLE 95 
               
               
                   
               
               
                   
                   
                 obs 
                   
                 Measure- 
               
               
                 Ex. 
                   
                 MS 
                 tR  
                 ment 
               
               
                 No. 
                 —B 
                 [M + 1]  
                 (min) 
                 Method 
               
               
                   
               
             
            
               
                 AC1 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 514.5 
                 3.47 
                 SA 
               
               
                   
               
               
                 AC2 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 540.6 
                 3.38 
                 SA 
               
               
                   
               
               
                 AC3 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 530.5 
                 3.52 
                 SA 
               
               
                   
               
               
                 AC4 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 526.7 
                 3.32 
                 SA 
               
               
                   
               
               
                 AC5 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 564.6 
                 3.65 
                 SA 
               
               
                   
               
               
                 AC6 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 521.7 
                 3.24 
                 SA 
               
               
                   
               
               
                 AC7 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 514.5 
                 3.34 
                 SA 
               
               
                   
               
               
                 AC8 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 530.5 
                 3.51 
                 SA 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
             
               
                 TABLE 96 
               
               
                   
               
               
                   
                   
                 obs 
                   
                 Measure- 
               
               
                 Ex. 
                   
                 MS 
                 tR  
                 ment 
               
               
                 No. 
                 —B 
                 [M + 1]  
                 (min) 
                 Method 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
               
            
               
                 AC9 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 526.7 
                 3.3 
                 SA 
               
               
                   
               
               
                 AC10 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 564.5 
                 3.66 
                 SA 
               
               
                   
               
               
                 AC11 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 521.7 
                 3.24 
                 SA 
               
               
                   
               
               
                 AC12 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 544.5 
                 3.59 
                 SA 
               
               
                   
               
               
                 AC13 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 540.6 
                 3.34 
                 SA 
               
               
                   
               
               
                 AC14 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 578.5 
                 3.74 
                 SA 
               
               
                   
               
               
                 AC15 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 528.6 
                 3.43 
                 SA 
               
               
                   
               
               
                 AC16 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 434.6 
                 2.85 
                 SA 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
             
               
                 TABLE 97 
               
               
                   
               
               
                   
                   
                   
                   
                 Measure- 
               
               
                 Ex.  
                   
                 obs MS 
                 tR  
                 ment 
               
               
                 No. 
                 —B 
                 [M + 1] 
                 (min) 
                 Method 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
               
            
               
                 AC17 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 448.6 
                 3 
                 SA 
               
               
                   
               
               
                 AC18 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 462.5 
                 3.13 
                 SA 
               
               
                   
               
               
                 AC19 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 460.5 
                 3.09 
                 SA 
               
               
                   
               
               
                 AC20 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 514.6 
                 3.33 
                 SA 
               
               
                   
               
               
                 AC21 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 532.6 
                 3.47 
                 SA 
               
               
                   
               
               
                 AC22 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 532.6 
                 3.45 
                 SA 
               
               
                   
               
               
                 AC23 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 532.5 
                 3.41 
                 SA 
               
               
                   
               
               
                 AC24 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 578.5 
                 3.67 
                 SA 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
             
               
                 TABLE 98 
               
               
                   
               
               
                   
                   
                   
                   
                 Measure- 
               
               
                 Ex.  
                   
                 obs MS 
                 tR  
                 ment 
               
               
                 No. 
                 —B 
                 [M + 1] 
                 (min) 
                 Method 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
               
            
               
                 AC25 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 578.5 
                 3.74 
                 SA 
               
               
                   
               
               
                 AC26 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 528.6 
                 3.46 
                 SA 
               
               
                   
               
               
                 AC27 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 528.5 
                 3.45 
                 SA 
               
               
                   
               
               
                 AC28 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 544.5 
                 3.54 
                 SA 
               
               
                   
               
               
                 AC29 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 544.5 
                 3.58 
                 SA 
               
               
                   
               
               
                 AC30 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 535.7 
                 3.31 
                 SA 
               
               
                   
               
               
                 AC31 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 535.6 
                 3.3 
                 SA 
               
               
                   
               
               
                 AC32 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 540.4 
                 3.45 
                 SA 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
             
               
                 TABLE 99 
               
               
                   
               
               
                   
                   
                   
                   
                 Measure- 
               
               
                 Ex.  
                   
                 obs MS 
                 tR 
                 ment 
               
               
                 No. 
                 —B 
                 [M + 1] 
                 (min) 
                 Method 
               
               
                   
               
             
            
               
                 AC33 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 566.4 
                 3.49 
                 SA 
               
               
                   
               
               
                 AC34 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 554.4 
                 3.55 
                 SA 
               
               
                   
               
               
                 AC35 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 570.5 
                 3.73 
                 SA 
               
               
                   
               
               
                 AC36 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 511.5 
                 2.62 
                 SA 
               
               
                   
               
               
                 AC37 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 527.3 
                 3.16 
                 SA 
               
               
                   
               
               
                 AC38 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 565.4 
                 3.42 
                 SA 
               
               
                   
               
               
                 AC39 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 531.4 
                 3.35 
                 SA 
               
               
                   
               
               
                 AC40 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 565.4 
                 3.61 
                 SA 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
             
               
                 TABLE 100 
               
               
                   
               
               
                   
                   
                   
                   
                 Measure- 
               
               
                 Ex.  
                   
                 obs MS 
                 tR 
                 ment 
               
               
                 No. 
                 —B 
                 [M + 1] 
                 (min) 
                 Method 
               
               
                   
               
             
            
               
                 AC41 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 536.5 
                 3.62 
                 SA 
               
               
                   
               
               
                 AC42 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 502.5 
                 3.23 
                 SA 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
             
               
                 TABLE 101 
               
               
                   
               
               
                   
                   
                   
                   
                 Measure- 
               
               
                 Ex.  
                   
                 obs MS 
                 tR 
                 ment 
               
               
                 No. 
                 —B 
                 [M + 1] 
                 (min) 
                 Method 
               
               
                   
               
             
            
               
                 AD1 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 550.4 
                 3.66 
                 SA 
               
               
                   
               
               
                 AD2 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 566.4 
                 3.83 
                 SA 
               
               
                   
               
               
                 AD3 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 562.6 
                 3.55 
                 SA 
               
               
                   
               
               
                 AD4 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 557.5 
                 3.55 
                 SA 
               
               
                   
               
               
                 AD5 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 550.6 
                 3.71 
                 SA 
               
               
                   
               
               
                 AD6 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 566.5 
                 3.85 
                 SA 
               
               
                   
               
               
                 AD7 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 562.5 
                 3.67 
                 SA 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
             
               
                 TABLE 102 
               
               
                   
               
               
                   
                   
                   
                   
                 Measure- 
               
               
                 Ex.  
                   
                 obs MS 
                 tR 
                 ment 
               
               
                 No. 
                 —B 
                 [M + 1] 
                 (min) 
                 Method 
               
               
                   
               
             
            
               
                 AD9 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 550.5 
                 3.68 
                 SA 
               
               
                   
               
               
                 AD10 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 566.5 
                 3.85 
                 SA 
               
               
                   
               
               
                 AD11 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 562.6 
                 3.63 
                 SA 
               
               
                   
               
               
                 AD12 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 557.5 
                 3.61 
                 SA 
               
               
                   
               
               
                 AD13 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 564.5 
                 3.67 
                 SA 
               
               
                   
               
               
                 AD14 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 580.5 
                 3.84 
                 SA 
               
               
                   
               
               
                 AD15 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 533.7 
                 3.34 
                 SA 
               
               
                   
               
               
                 AD16 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 470.5 
                 3.05 
                 SA 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
             
               
                 TABLE 103 
               
               
                   
               
               
                   
                   
                   
                   
                 Measure- 
               
               
                 Ex.  
                   
                 obs MS 
                 tR 
                 ment 
               
               
                 No. 
                 —B 
                 [M + 1] 
                 (min) 
                 Method 
               
               
                   
               
             
            
               
                 AD17 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 484.5 
                 3.21 
                 SA 
               
               
                   
               
               
                 AD18 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 538.7 
                 3.55 
                 SA 
               
               
                   
               
               
                 AD19 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 568.6 
                 3.84 
                 SA 
               
               
                   
               
               
                 AD20 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 568.5 
                 3.8 
                 SA 
               
               
                   
               
               
                 AD21 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 568.5 
                 3.63 
                 SA 
               
               
                   
               
               
                 AD22  
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 568.6 
                 3.73 
                 SA 
               
               
                   
               
               
                 AD23 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 600.6 
                 3.87 
                 SA 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
             
               
                 TABLE 104 
               
               
                   
               
               
                   
                   
                   
                   
                 Measure- 
               
               
                 Ex.  
                   
                 obs MS 
                 tR 
                 ment 
               
               
                 No. 
                 —B 
                 [M + 1] 
                 (min) 
                 Method 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
               
            
               
                 AD25 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 600.5 
                 4 
                 SA 
               
               
                   
               
               
                 AD26 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 568.6 
                 3.75 
                 SA 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
             
               
                 TABLE 105 
               
               
                   
               
               
                   
                   
                   
                   
                 Measure- 
               
               
                 Ex.  
                   
                 obs MS 
                 tR 
                 ment 
               
               
                 No. 
                 —B 
                 [M + 1] 
                 (min) 
                 Method 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
               
            
               
                 AE1 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 529.4 
                 2.99 
                 SB 
               
               
                   
               
               
                 AE2 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 529.2 
                 3.11 
                 SB 
               
               
                   
               
               
                 AE3 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 529.2 
                 3.03 
                 SB 
               
               
                   
               
               
                 AE4 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 545.4 
                 3.15 
                 SB 
               
               
                   
               
               
                 AE5 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 545.4 
                 3.24 
                 SB 
               
               
                   
               
               
                 AE6 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 545.4 
                 3.21 
                 SB 
               
               
                   
               
               
                 AE7 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 541.5 
                 3.09 
                 SB 
               
               
                   
               
               
                 AE8 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 541.5 
                 3.01 
                 SB 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
             
               
                 TABLE 106 
               
               
                   
               
               
                   
                   
                   
                   
                 Measure- 
               
               
                 Ex.  
                   
                 obs MS 
                 tR 
                 ment 
               
               
                 No. 
                 —B 
                 [M + 1] 
                 (min) 
                 Method 
               
               
                   
               
             
            
               
                 AE9 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 536.4 
                 2.88 
                 SB 
               
               
                   
               
               
                 AE10 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 536.4 
                 3.03 
                 SB 
               
               
                   
               
               
                 AE11 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 536.4 
                 3.01 
                 SB 
               
               
                   
               
               
                 AE12 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 536.4 
                 3.01 
                 SB 
               
               
                   
               
               
                 AE13 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 547.6 
                 3.69 
                 SB 
               
               
                   
               
               
                 AE14 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 547.6 
                 3.47 
                 SB 
               
               
                   
               
               
                 AE15 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 547.6 
                 3.76 
                 SB 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
             
               
                 TABLE 107 
               
               
                   
               
               
                   
                   
                   
                   
                 Measure- 
               
               
                 Ex. 
                   
                 obs MS 
                 tR 
                 ment 
               
               
                 No. 
                 —B 
                 [M + 1] 
                 (min) 
                 Method 
               
               
                   
               
             
            
               
                 AE17 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 539.8 
                 3.69 
                 SB 
               
               
                   
               
               
                 AE18 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 539.8 
                 3.69 
                 SB 
               
               
                   
               
               
                 AE19 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 543.7 
                 3.63 
                 SB 
               
               
                   
               
               
                 AE20 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 543.7 
                 3.67 
                 SB 
               
               
                   
               
               
                 AE21 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 559.7 
                 4.01 
                 SB 
               
               
                   
               
               
                 AE22 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 555.8 
                 3.61 
                 SB 
               
               
                   
               
               
                 AE23 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 555.8 
                 3.57 
                 SB 
               
               
                   
               
               
                 AE24 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 543.4 
                 3.01 
                 SB 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
             
               
                 TABLE 108 
               
               
                   
               
               
                   
                   
                   
                   
                 Measure- 
               
               
                 Ex.  
                   
                 obs MS 
                 tR 
                 ment 
               
               
                 No. 
                 —B 
                 [M + 1] 
                 (min) 
                 Method 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
               
            
               
                 AE25 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 559.4 
                 3.11 
                 SB 
               
               
                   
               
               
                 AE26 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 559.4 
                 3.15 
                 SB 
               
               
                   
               
               
                 AE27 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 555.2 
                 2.94 
                 SB 
               
               
                   
               
               
                 AE28 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 565.6 
                 3.14 
                 SB 
               
               
                   
               
               
                 AE29 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 539.5 
                 3.07 
                 SB 
               
               
                   
               
               
                 AE30 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 512.4 
                 2.3  
                 SB 
               
               
                   
               
               
                 AE31 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 526.4 
                 2.32 
                 SB 
               
               
                   
               
               
                 AE32 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 580.4 
                 3.11 
                 SB 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
             
               
                 TABLE 109 
               
               
                   
               
               
                   
                   
                   
                   
                 Measure- 
               
               
                 Ex.  
                   
                 obs MS 
                 tR 
                 ment 
               
               
                 No. 
                 —B 
                 [M + 1] 
                 (min) 
                 Method 
               
               
                   
               
             
            
               
                 AE33 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 542.6 
                 2.63 
                 SB 
               
               
                   
               
               
                 AE34 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 546.2 
                 2.9  
                 SB 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
             
               
                 TABLE 110 
               
               
                   
               
               
                   
                   
                   
                   
                 Measure- 
               
               
                 Ex.  
                   
                 obs MS 
                 tR 
                 ment 
               
               
                 No. 
                 —B 
                 [M + 1] 
                 (min) 
                 Method 
               
               
                   
               
             
            
               
                 AF1 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 537.6 
                 3.47 
                 SB 
               
               
                   
               
               
                 AF2 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 537.6 
                 2.73 
                 SB 
               
               
                   
               
               
                 AF3 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 537.6 
                 2.94 
                 SB 
               
               
                   
               
               
                 AF4 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 537.6 
                 3.74 
                 SB 
               
               
                   
               
               
                 AF5 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 487.4 
                 2.38 
                 SB 
               
               
                   
               
               
                 AF6 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 494.4 
                 2.67 
                 SB 
               
               
                   
               
               
                 AF7 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 494.4 
                 3.09 
                 SB 
               
               
                   
               
               
                 AF8 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 500.3 
                 2.30 
                 SB 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
             
               
                 TABLE 111 
               
               
                   
               
               
                   
                   
                   
                   
                 Measure- 
               
               
                 Ex.  
                   
                 obs MS 
                 tR 
                 ment 
               
               
                 No. 
                 —B 
                 [M + 1] 
                 (min) 
                 Method 
               
               
                   
               
             
            
               
                 AF9 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 470.3 
                 2.61 
                 SB 
               
               
                   
               
               
                 AF10 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 494.4 
                 2.94 
                 SB 
               
               
                   
               
            
           
         
       
     
     
       
         
         
             
             
         
       
     
     
       
         
           
               
               
               
               
               
             
               
                 TABLE 112 
               
               
                   
               
               
                 Ex. 
                   
                 obs MS 
                 tR  
                 Measurement 
               
               
                 No. 
                 —B 
                 [M + 1] 
                 (min) 
                 Method 
               
               
                   
               
             
            
               
                 AG1 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 529.4 
                 3.05 
                 SB 
               
               
                   
               
               
                 AG2 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 529.4 
                 3.13 
                 SB 
               
               
                   
               
               
                 AG3 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 529.4 
                 3.05 
                 SB 
               
               
                   
               
               
                 AG4 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 545.4 
                 3.15 
                 SB 
               
               
                   
               
               
                 AG5 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 545.4 
                 3.24 
                 SB 
               
               
                   
               
               
                 AG6 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 545.4 
                 3.21 
                 SB 
               
               
                   
               
               
                 AG7 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 541.5 
                 3.07 
                 SB 
               
               
                   
               
               
                 AG8 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 541.5 
                 3.01 
                 SB 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
             
               
                 TABLE 113 
               
               
                   
               
               
                 Ex. 
                   
                 obs MS 
                 tR 
                 Measurement 
               
               
                 No. 
                 —B 
                 [M + 1] 
                 (min) 
                 Method 
               
               
                   
               
             
            
               
                 AG9 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 541.5 
                 2.94 
                 SB 
               
               
                   
               
               
                 AG10 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 536.4 
                 2.9  
                 SB 
               
               
                   
               
               
                 AG11 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 536.4 
                 3.03 
                 SB 
               
               
                   
               
               
                 AG12 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 536.4 
                 3.03 
                 SB 
               
               
                   
               
               
                 AG13 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 547.4 
                 3.01 
                 SB 
               
               
                   
               
               
                 AG14 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 547.4 
                 3.11 
                 SB 
               
               
                   
               
               
                 AG15 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 547.4 
                 2.88 
                 SB 
               
               
                   
               
               
                 AG16 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 547.4 
                 3.17 
                 SB 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
             
               
                 TABLE 114 
               
               
                   
               
               
                   
                   
                   
                   
                 Meas- 
               
               
                   
                   
                 obs MS 
                 tR  
                 urement 
               
               
                 Ex. No. 
                 —B 
                 [M + 1] 
                 (min) 
                 Method 
               
               
                   
               
             
            
               
                 AG17 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 547.4 
                 3.26 
                 SB 
               
               
                   
               
               
                 AG18 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 539.5 
                 3.11 
                 SB 
               
               
                   
               
               
                 AG19  
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 539.5 
                 3.09 
                 SB 
               
               
                   
               
               
                 AG20 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 543.4 
                 3.01 
                 SB 
               
               
                   
               
               
                 AG21 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 543.4 
                 3.01 
                 SB 
               
               
                   
               
               
                 AG22  
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 559.4 
                 3.15 
                 SB 
               
               
                   
               
               
                 AG23 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 555.2 
                 3.03 
                 SB 
               
               
                   
               
               
                 AG24 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 555.2 
                 2.96 
                 SB 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
             
               
                 TABLE 115 
               
               
                   
               
               
                   
                   
                 obs MS 
                   
                 Measurement 
               
               
                 Ex. No. 
                 —B 
                 [M + 1] 
                 tR (min) 
                 Method 
               
               
                   
               
             
            
               
                 AH1 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 537.6 
                 3.47 
                 SB 
               
               
                   
               
               
                 AH2 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 537.6 
                 2.73 
                 SB 
               
               
                   
               
               
                 AH3 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 537.6 
                 2.88 
                 SB 
               
               
                   
               
               
                 AH4 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 537.6 
                 3.74 
                 SB 
               
               
                   
               
               
                 AH5 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 487.4 
                 2.42 
                 SB 
               
               
                   
               
               
                 AH6 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 494.4 
                 3.34 
                 SB 
               
               
                   
               
               
                 AH7 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 494.4 
                 2.67 
                 SB 
               
               
                   
               
               
                 AH8 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 494.4 
                 3.09 
                 SB 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
             
               
                 TABLE 116 
               
               
                   
               
               
                   
                   
                 obs MS 
                   
                 Measurement 
               
               
                 Ex. No. 
                 —B 
                 [M + 1] 
                 tR (min) 
                 Method 
               
               
                   
               
             
            
               
                 AH9 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 500.3 
                 2.28 
                 SB 
               
               
                   
               
               
                 AH10 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 470.3 
                 2.61 
                 SB 
               
               
                   
               
               
                 AH11 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 494.4 
                 2.94 
                 SB 
               
               
                   
               
            
           
         
       
     
     
       
         
         
             
             
         
       
     
     
       
         
           
               
               
               
               
               
             
               
                 TABLE 117 
               
               
                   
               
               
                   
                   
                 obs MS 
                   
                 Measurement 
               
               
                 Ex. No. 
                 —B 
                 [M + 1] 
                 tR (min) 
                 Method 
               
               
                   
               
             
            
               
                 AI1 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 560.6 
                 3.64 
                 SA 
               
               
                   
               
               
                 AI2 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 560.5 
                 3.72 
                 SA 
               
               
                   
               
               
                 AI3 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 560.5 
                 3.72 
                 SA 
               
               
                   
               
               
                 AI4 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 544.6 
                 3.6  
                 SA 
               
               
                   
               
               
                 AI5 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 544.6 
                 3.6  
                 SA 
               
               
                   
               
               
                 AI6 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 544.5 
                 3.58 
                 SA 
               
               
                   
               
               
                 AI7 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 556.5 
                 3.7  
                 SA 
               
               
                   
               
               
                 AI8 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 556.5 
                 3.57 
                 SA 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
             
               
                 TABLE 118 
               
               
                   
               
               
                   
                   
                   
                   
                 Meas- 
               
               
                   
                   
                 obs MS 
                 tR 
                 urement 
               
               
                 Ex. No. 
                 —B 
                 [M + 1] 
                 (min) 
                 Method 
               
               
                   
               
             
            
               
                 AI9 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 556.5 
                 3.56 
                 SA 
               
               
                   
               
               
                 AI10 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 594.5 
                 3.78 
                 SA 
               
               
                   
               
               
                 AI11 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 594.4 
                 3.89 
                 SA 
               
               
                   
               
               
                 AI12 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 594.4 
                 3.91 
                 SA 
               
               
                   
               
               
                 AI13 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 562.5 
                 3.66 
                 SA 
               
               
                   
               
               
                 AI14 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 562.6 
                 3.68 
                 SA 
               
               
                   
               
               
                 AI15 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 562.5 
                 3.67 
                 SA 
               
               
                   
               
               
                 AI16 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 608.5 
                 3.98 
                 SA 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
             
               
                 TABLE 119 
               
               
                   
               
               
                 Ex. 
                   
                 obs MS 
                 tR 
                 Measurement 
               
               
                 No. 
                 —B 
                 [M + 1] 
                 (min) 
                 Method 
               
               
                   
               
             
            
               
                 AI17 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 558.6 
                 3.68 
                 SA 
               
               
                   
               
               
                 AI18 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 574.5 
                 3.79 
                 SA 
               
               
                   
               
               
                 AI19 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 570.6 
                 3.63 
                 SA 
               
               
                   
               
               
                 AI20 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 570.6 
                 3.58 
                 SA 
               
               
                   
               
               
                 AI21 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 464.4 
                 3.13 
                 SA 
               
               
                   
               
               
                 AI22 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 478.5 
                 3.31 
                 SA 
               
               
                   
               
               
                 AI23 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 492.6 
                 3.42 
                 SA 
               
               
                   
               
               
                 AI24 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 596.5 
                 3.7  
                 SA 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
             
               
                 TABLE 120 
               
               
                   
               
               
                 Ex.  
                   
                 obs MS 
                 tR  
                 Measurement 
               
               
                 No. 
                 —B 
                 [M + 1] 
                 (min) 
                 Method 
               
               
                   
               
             
            
               
                 AI25 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 584.6 
                 3.8  
                 SA 
               
               
                   
               
               
                 AI26 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 600.5 
                 3.96 
                 SA 
               
               
                   
               
               
                 AI27 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 541.6 
                 2.84 
                 SA 
               
               
                   
               
               
                 AI28 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 557.6 
                 3.4  
                 SA 
               
               
                   
               
               
                 AI29 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 595.5 
                 3.66 
                 SA 
               
               
                   
               
               
                 AI30 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 561.7 
                 3.52 
                 SA 
               
               
                   
               
               
                 AI31 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 595.4 
                 3.71 
                 SA 
               
               
                   
               
               
                 AI32  
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 566.5 
                 4   
                 SA 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
             
               
                 TABLE 121 
               
               
                   
               
               
                   
                   
                 obs MS 
                   
                 Measurement 
               
               
                 Ex. No. 
                 —B 
                 [M + 1] 
                 tR (min) 
                 Method 
               
               
                   
               
             
            
               
                 AI33 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 532.6 
                 3.54 
                 SA 
               
               
                   
               
               
                 AI34 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 532.6 
                 3.54 
                 SA 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
             
               
                 TABLE 122 
               
               
                   
               
               
                   
                   
                   
                   
                 Meas- 
               
               
                   
                   
                 obs MS 
                   
                 urement 
               
               
                 Ex. No. 
                 —B 
                 [M + 1] 
                 tR (min) 
                 Method 
               
               
                   
               
             
            
               
                 AJ1 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 596.4 
                 4.01 
                 SA 
               
               
                   
               
               
                 AJ2 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 596.4 
                 4.12 
                 SA 
               
               
                   
               
               
                 AJ3 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 596.5 
                 4.14 
                 SA 
               
               
                   
               
               
                 AJ4 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 580.4 
                 3.93 
                 SA 
               
               
                   
               
               
                 AJ5 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 580.4 
                 3.97 
                 SA 
               
               
                   
               
               
                 AJ6 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 592.4 
                 3.83 
                 SA 
               
               
                   
               
               
                 AJ7 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 592.3 
                 3.97 
                 SA 
               
               
                   
               
               
                 AJ8 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 592.5 
                 3.93 
                 SA 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
             
               
                 TABLE 123 
               
               
                   
               
               
                   
                   
                   
                   
                 Meas- 
               
               
                   
                   
                 obs MS 
                   
                 urement 
               
               
                 Ex. No. 
                 —B 
                 [M + 1] 
                 tR (min) 
                 Method 
               
               
                   
               
             
            
               
                 AJ9 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 630.5 
                 4.11 
                 SA 
               
               
                   
               
               
                 AJ10 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 630.5 
                 4.21 
                 SA 
               
               
                   
               
               
                 AJ11 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 630.5 
                 4.27 
                 SA 
               
               
                   
               
               
                 AJ12 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 598.6 
                 4.02 
                 SA 
               
               
                   
               
               
                 AJ13 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 598.6 
                 4.06 
                 SA 
               
               
                   
               
               
                 AJ14 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 598.5 
                 4   
                 SA 
               
               
                   
               
               
                 AJ15 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 598.6 
                 4.09 
                 SA 
               
               
                   
               
               
                 AJ16 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 598.6 
                 3.91 
                 SA 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
             
               
                 TABLE 124 
               
               
                   
               
               
                   
                   
                   
                   
                 Meas- 
               
               
                   
                   
                 obs MS 
                   
                 urement 
               
               
                 Ex. No. 
                 —B 
                 [M + 1] 
                 tR (min) 
                 Method 
               
               
                   
               
             
            
               
                 AJ17 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 594.4 
                 3.89 
                 SA 
               
               
                   
               
               
                 AJ18 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 610.3 
                 4.05 
                 SA 
               
               
                   
               
               
                 AJ19 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 500.5 
                 3.33 
                 SA 
               
               
                   
               
               
                 AJ20 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 514.5 
                 3.47 
                 SA 
               
               
                   
               
               
                 AJ21 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 528.5 
                 3.58 
                 SA 
               
               
                   
               
               
                 AJ22 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 526.5 
                 3.54 
                 SA 
               
               
                   
               
               
                 AJ23 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 568.3 
                 3.76 
                 SA 
               
               
                   
               
               
                 AJ24 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 563.6 
                 3.46 
                 SA 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
             
               
                 TABLE 125 
               
               
                   
               
               
                   
                   
                 obs MS 
                   
                 Measurement 
               
               
                 Ex. No. 
                 —B 
                 [M + 1] 
                 tR (min) 
                 Method 
               
               
                   
               
             
            
               
                 AJ25 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 528.6 
                 3.67 
                 SA 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
             
               
                 TABLE 126 
               
               
                   
               
               
                   
                   
                   
                   
                 Meas- 
               
               
                   
                   
                 obs MS 
                 tR  
                 urement 
               
               
                 Ex. No. 
                 —B 
                 [M + 1] 
                 (min) 
                 Method 
               
               
                   
               
             
            
               
                 AK1 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 559.7 
                 3.78 
                 SB 
               
               
                   
               
               
                 AK2 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 559.7 
                 3.86 
                 SB 
               
               
                   
               
               
                 AK3 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 575.7 
                 3.95 
                 SB 
               
               
                   
               
               
                 AK4 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 575.7 
                 0.69 
                 SB 
               
               
                   
               
               
                 AK5 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 575.4  
                 3.38 
                 SB 
               
               
                   
               
               
                 AK6 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 571.7 
                 3.9  
                 SB 
               
               
                   
               
               
                 AK7 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 571.7 
                 3.78 
                 SB 
               
               
                   
               
               
                 AK8 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 571.7 
                 3.72 
                 SB 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
             
               
                 TABLE 127 
               
               
                   
               
               
                   
                   
                 obs 
                   
                 Measure- 
               
               
                 Ex. 
                   
                 MS 
                 tR  
                 ment 
               
               
                 No. 
                 —B 
                 [M + 1] 
                 (min) 
                 Method 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
               
            
               
                 AK9 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 566.7 
                 3.65 
                 SB 
               
               
                   
               
               
                 AK10 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 566.7 
                 3.8 
                 SB 
               
               
                   
               
               
                 AK11 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 566.7 
                 3.76 
                 SB 
               
               
                   
               
               
                 AK12 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 577.9 
                 3.8 
                 SB 
               
               
                   
               
               
                 AK13 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 577.9 
                 3.84 
                 SB 
               
               
                   
               
               
                 AK14 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 577.9 
                 0.65 
                 SB 
               
               
                   
               
               
                 AK15 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 577.9 
                 0.65 
                 SB 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
             
               
                 TABLE 128 
               
               
                   
               
               
                   
                   
                 obs 
                   
                 Measure- 
               
               
                 Ex. 
                   
                 MS 
                 tR  
                 ment 
               
               
                 No. 
                 —B 
                 [M + 1] 
                 (min) 
                 Method 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
               
            
               
                 AK17 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 569.5 
                 3.32 
                 SB 
               
               
                   
               
               
                 AK18 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 569.5 
                 3.3 
                 SB 
               
               
                   
               
               
                 AK19 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 573.4 
                 3.19 
                 SB 
               
               
                   
               
               
                 AK20 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 573.4 
                 3.21 
                 SB 
               
               
                   
               
               
                 AK21 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 589.4 
                 3.36 
                 SB 
               
               
                   
               
               
                 AK22 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 585.2 
                 3.21 
                 SB 
               
               
                   
               
               
                 AK23 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 585.2 
                 3.17 
                 SB 
               
               
                   
               
               
                 AK24 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 573.4 
                 3.24 
                 SB 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
             
               
                 TABLE 129 
               
               
                   
               
               
                   
                   
                   
                   
                 Measurement 
               
               
                 Ex. No. 
                 —B 
                 obs MS [M + 1] 
                 tR (min) 
                 Method 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
               
            
               
                 AK25 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 589.4 
                 3.32 
                 SB 
               
               
                   
               
               
                 AK26 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 589.4 
                 3.36 
                 SB 
               
               
                   
               
               
                 AK27 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 585.2 
                 3.17 
                 SB 
               
               
                   
               
               
                 AK28 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 556.3 
                 2.44 
                 SB 
               
               
                   
               
               
                 AK29 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 610.4 
                 3.3 
                 SB 
               
               
                   
               
               
                 AK30 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 572.3 
                 2.82 
                 SB 
               
               
                   
               
               
                 AK31 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 560.2 
                 2.9 
                 SB 
               
               
                   
               
               
                 AK32 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 576.2 
                 3.11 
                 SB 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
             
               
                 TABLE 130 
               
               
                   
               
               
                   
                   
                 obs 
                   
                 Measure- 
               
               
                 Ex. 
                   
                 MS 
                 tR  
                 ment 
               
               
                 No. 
                 —B 
                 [M + 1] 
                 (min) 
                 Method 
               
               
                   
               
             
            
               
                 AK33 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 556.3 
                 2.51 
                 SB 
               
               
                   
               
               
                 AK34 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 595.3 
                 3.35 
                 SB 
               
               
                   
               
               
                 AK35 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 542.3 
                 2.44 
                 SB 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
             
               
                 TABLE 131 
               
               
                   
               
               
                   
                   
                 obs 
                   
                 Measure- 
               
               
                 Ex. 
                   
                 MS 
                 tR  
                 ment 
               
               
                 No. 
                 —B 
                 [M + 1] 
                 (min) 
                 Method 
               
               
                   
               
             
            
               
                 AL1 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 567.3 
                 3.69 
                 SB 
               
               
                   
               
               
                 AL2 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 567.3 
                 3.42 
                 SB 
               
               
                   
               
               
                 AL3 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 567.3 
                 3.65 
                 SB 
               
               
                   
               
               
                 AL4 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 567.5 
                 3.97 
                 SB 
               
               
                   
               
               
                 AL5 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 517.4 
                 2.94 
                 SB 
               
               
                   
               
               
                 AL6 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 524.4 
                 3.57 
                 SB 
               
               
                   
               
               
                 AL7 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 524.4 
                 3.32 
                 SB 
               
               
                   
               
               
                 AL8 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 524.4 
                 3.28 
                 SB 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
             
               
                 TABLE 132 
               
               
                   
               
               
                   
                   
                 obs 
                   
                 Measure- 
               
               
                 Ex. 
                   
                 MS 
                 tR  
                 ment 
               
               
                 No. 
                 —B 
                 [M + 1] 
                 (min) 
                 Method 
               
               
                   
               
             
            
               
                 AL9 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 530.3 
                 2.40 
                 SB 
               
               
                   
               
               
                 AL10 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 500.3 
                 2.99 
                 SB 
               
               
                   
               
               
                 AL11 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 524.4 
                 3.40 
                 SB 
               
               
                   
               
            
           
         
       
     
     
       
         
         
             
             
         
       
     
     
       
         
           
               
               
               
               
               
             
               
                 TABLE 133 
               
               
                   
               
               
                   
                   
                 obs 
                   
                 Measure- 
               
               
                 Ex. 
                   
                 MS 
                 tR  
                 ment 
               
               
                 No. 
                 —B 
                 [M + 1] 
                 (min) 
                 Method 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
               
            
               
                 AM1 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 560.6 
                 3.84 
                 SA 
               
               
                   
               
               
                 AM2 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 560.5 
                 3.74 
                 SA 
               
               
                   
               
               
                 AM3 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 544.5 
                 3.56 
                 SA 
               
               
                   
               
               
                 AM4 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 544.5 
                 3.58 
                 SA 
               
               
                   
               
               
                 AM5 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 544.5 
                 3.56 
                 SA 
               
               
                   
               
               
                 AM6 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 556.5 
                 3.5 
                 SA 
               
               
                   
               
               
                 AM7 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 556.5 
                 3.56 
                 SA 
               
               
                   
               
               
                 AM8 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 556.5 
                 3.54 
                 SA 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
             
               
                 TABLE 134 
               
               
                   
               
               
                   
                   
                 obs 
                   
                 Measure- 
               
               
                 Ex. 
                   
                 MS 
                 tR  
                 ment 
               
               
                 No. 
                 —B 
                 [M + 1] 
                 (min) 
                 Method 
               
               
                   
               
             
            
               
                 AM9 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 594.4 
                 3.77 
                 SA 
               
               
                   
               
               
                 AM10 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 594.4 
                 3.87 
                 SA 
               
               
                   
               
               
                 AM11 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 594.4 
                 3.88 
                 SA 
               
               
                   
               
               
                 AM12 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 551.5 
                 3.46 
                 SA 
               
               
                   
               
               
                 AM13 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 551.6 
                 3.48 
                 SA 
               
               
                   
               
               
                 AM14 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 608.5 
                 3.92 
                 SA 
               
               
                   
               
               
                 AM15 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 608.5 
                 3.97 
                 SA 
               
               
                   
               
               
                 AM16 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 608.5 
                 3.95 
                 SA 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
             
               
                 TABLE 135 
               
               
                   
               
               
                   
                   
                 obs 
                   
                 Measure- 
               
               
                 Ex. 
                   
                 MS 
                 tR  
                 ment 
               
               
                 No. 
                 —B 
                 [M + 1] 
                 (min) 
                 Method 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
               
            
               
                 AM17 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 558.6 
                 3.68 
                 SA 
               
               
                   
               
               
                 AM18 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 558.5 
                 3.66 
                 SA 
               
               
                   
               
               
                 AM19 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 558.6 
                 3.64 
                 SA 
               
               
                   
               
               
                 AM20 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 574.6 
                 3.8 
                 SA 
               
               
                   
               
               
                 AM21 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 574.6 
                 3.82 
                 SA 
               
               
                   
               
               
                 AM22 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 574.6 
                 3.79 
                 SA 
               
               
                   
               
               
                 AM23 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 565.5 
                 3.55 
                 SA 
               
               
                   
               
               
                 AM24 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 565.5 
                 3.52 
                 SA 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
             
               
                 TABLE 136 
               
               
                   
               
               
                   
                   
                 obs 
                   
                 Measure- 
               
               
                 Ex. 
                   
                 MS 
                 tR  
                 ment 
               
               
                 No. 
                 —B 
                 [M + 1] 
                 (min) 
                 Method 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
               
            
               
                 AM25 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 570.6 
                 3.67 
                 SA 
               
               
                   
               
               
                 AM26 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 570.6 
                 3.6 
                 SA 
               
               
                   
               
               
                 AM27 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 570.6 
                 3.58 
                 SA 
               
               
                   
               
               
                 AM28 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 464.5 
                 3.1 
                 SA 
               
               
                   
               
               
                 AM29 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 478.5 
                 3.27 
                 SA 
               
               
                   
               
               
                 AM30 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 492.5 
                 3.42 
                 SA 
               
               
                   
               
               
                 AM31 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 596.5 
                 3.73 
                 SA 
               
               
                   
               
               
                 AM32 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 541.5 
                 2.91 
                 SA 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
             
               
                 TABLE 137 
               
               
                   
               
               
                   
                   
                 obs 
                   
                 Measure- 
               
               
                 Ex. 
                   
                 MS 
                 tR  
                 ment 
               
               
                 No. 
                 —B 
                 [M + 1] 
                 (min) 
                 Method 
               
               
                   
               
             
            
               
                 AM33 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 557.5 
                 3.38 
                 SA 
               
               
                   
               
               
                 AM34 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 595.4 
                 3.62 
                 SA 
               
               
                   
               
               
                 AM35 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 561.6 
                 3.49 
                 SA 
               
               
                   
               
               
                 AM36 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 595.5 
                 3.68 
                 SA 
               
               
                   
               
               
                 AM37 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 566.4 
                 3.83 
                 SA 
               
               
                   
               
               
                 AM38 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 532.6 
                 3.51 
                 SA 
               
               
                   
               
               
                 AM39 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 554.6 
                 3.78 
                 SA 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
             
               
                 TABLE 138 
               
               
                   
               
               
                   
                   
                 obs 
                   
                 Measure- 
               
               
                 Ex. 
                   
                 MS 
                 tR  
                 ment 
               
               
                 No. 
                 —B 
                 [M + 1] 
                 (min) 
                 Method 
               
               
                   
               
             
            
               
                 AN1 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 596.5 
                 4.01 
                 SA 
               
               
                   
               
               
                 AN2 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 596.5 
                 4.13 
                 SA 
               
               
                   
               
               
                 AN3 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 596.4 
                 4.14 
                 SA 
               
               
                   
               
               
                 AN4 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 580.4 
                 3.91 
                 SA 
               
               
                   
               
               
                 AN5 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 580.4 
                 3.97 
                 SA 
               
               
                   
               
               
                 AN6 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 592.4 
                 3.81 
                 SA 
               
               
                   
               
               
                 AN7 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 592.4 
                 3.95 
                 SA 
               
               
                   
               
               
                 AN8 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 592.6 
                 3.92 
                 SA 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
             
               
                 TABLE 139 
               
               
                   
               
               
                   
                   
                 obs 
                   
                 Measure- 
               
               
                 Ex. 
                   
                 MS 
                 tR  
                 ment 
               
               
                 No. 
                 —B 
                 [M + 1] 
                 (min) 
                 Method 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
               
            
               
                 AN9 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 630.5 
                 4.1 
                 SA 
               
               
                   
               
               
                 AN10 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 630.5 
                 4.21 
                 SA 
               
               
                   
               
               
                 AN11 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 630.3 
                 4.25 
                 SA 
               
               
                   
               
               
                 AN12 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 587.6 
                 3.76 
                 SA 
               
               
                   
               
               
                 AN13 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 587.6 
                 3.82 
                 SA 
               
               
                   
               
               
                 AN14 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 587.4 
                 3.84 
                 SA 
               
               
                   
               
               
                 AN15 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 598.6 
                 3.99 
                 SA 
               
               
                   
               
               
                 AN16 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 598.6 
                 4.06 
                 SA 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
             
               
                 TABLE 140 
               
               
                   
               
               
                   
                   
                 obs 
                   
                 Measure- 
               
               
                 Ex. 
                   
                 MS 
                 tR  
                 ment 
               
               
                 No. 
                 —B 
                 [M + 1] 
                 (min) 
                 Method 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
               
            
               
                 AN17 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 598.3 
                 3.99 
                 SA 
               
               
                   
               
               
                 AN18 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 598.5 
                 4.08 
                 SA 
               
               
                   
               
               
                 AN19 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 598.6 
                 3.9 
                 SA 
               
               
                   
               
               
                 AN20 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 594.4 
                 3.9 
                 SA 
               
               
                   
               
               
                 AN21 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 610.3 
                 4.06 
                 SA 
               
               
                   
               
               
                 AN22 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 500.6 
                 3.32 
                 SA 
               
               
                   
               
               
                 AN23 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 514.6 
                 3.45 
                 SA 
               
               
                   
               
               
                 AN24 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 528.5 
                 3.6 
                 SA 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
             
               
                 TABLE 141 
               
               
                   
               
               
                   
                   
                 obs MS 
                   
                 Measurement 
               
               
                 Ex. No. 
                 —B 
                 [M + 1] 
                 tR (min) 
                 Method 
               
               
                   
               
             
            
               
                 AN25 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 526.6 
                 3.53 
                 SA 
               
               
                   
               
               
                 AN26 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 568.6 
                 3.76 
                 SA 
               
               
                   
               
               
                 AN27 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 563.5 
                 3.47 
                 SA 
               
               
                   
               
               
                 AN28 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 528.5 
                 3.64 
                 SA 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
             
               
                 TABLE 142 
               
               
                   
               
               
                 Ex. 
                   
                 obs MS 
                 tR 
                 Measurement 
               
               
                 No. 
                 —B 
                 [M + 1] 
                 (min) 
                 Method 
               
               
                   
               
             
            
               
                 AO1 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 559.4 
                 3.23 
                 SA 
               
               
                   
               
               
                 AO2 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 559.6 
                 3.78 
                 SA 
               
               
                   
               
               
                 AO3 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 559.6 
                 3.69 
                 SA 
               
               
                   
               
               
                 AO4 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 575.5 
                 3.81 
                 SA 
               
               
                   
               
               
                 AO5 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 575.5 
                 3.88 
                 SA 
               
               
                   
               
               
                 AO6 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 575.6 
                 3.86 
                 SA 
               
               
                   
               
               
                 AO7 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 571.5 
                 3.79 
                 SA 
               
               
                   
               
               
                 AO8 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 571.5 
                 3.66 
                 SA 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
             
               
                 TABLE 143 
               
               
                   
               
               
                 Ex. 
                   
                 obs MS 
                 tR  
                 Measurement 
               
               
                 No. 
                 —B 
                 [M + 1] 
                 (min) 
                 Method 
               
               
                   
               
             
            
               
                 AO9 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 571.5 
                 3.58 
                 SA 
               
               
                   
               
               
                 AO10 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 566.5 
                 3.52 
                 SA 
               
               
                   
               
               
                 AO11 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 566.7 
                 3.66 
                 SA 
               
               
                   
               
               
                 AO12 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 566.5 
                 3.61 
                 SA 
               
               
                   
               
               
                 AO13 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 577.6 
                 3.65 
                 SA 
               
               
                   
               
               
                 AO14 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 577.6 
                 3.81 
                 SA 
               
               
                   
               
               
                 AO15 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 577.9 
                 3.69 
                 SB 
               
               
                   
               
               
                 AO16 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 577.5 
                 3.8  
                 SA 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
             
               
                 TABLE 144 
               
               
                   
               
               
                   
                   
                   
                   
                 Mea- 
               
               
                   
                   
                   
                   
                 sure- 
               
               
                   
                   
                   
                   
                 ment 
               
               
                 Ex. 
                   
                 obs MS 
                 tR 
                 Me- 
               
               
                 No. 
                 —B 
                 [M + 1] 
                 (min) 
                 thod 
               
               
                   
               
             
            
               
                 AO17 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 577.9 
                 4.01 
                 SB 
               
               
                   
               
               
                 AO18 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 569.8 
                 3.9  
                 SB 
               
               
                   
               
               
                 AO19 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 569.8 
                 3.95 
                 SB 
               
               
                   
               
               
                 AO20 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 573.7 
                 3.8  
                 SB 
               
               
                   
               
               
                 AO21 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 573.7 
                 3.82 
                 SB 
               
               
                   
               
               
                 AO22 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 589.4 
                 4.01 
                 SB 
               
               
                   
               
               
                 AO23 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 585.7 
                 3.86 
                 SB 
               
               
                   
               
               
                 AO24 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 585.5 
                 3.17 
                 SB 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
             
               
                 TABLE 145 
               
               
                   
               
               
                 Ex. 
                   
                 obs MS 
                 tR 
                 Measurement 
               
               
                 No. 
                 —B 
                 [M + 1] 
                 (min) 
                 Method 
               
               
                   
               
             
            
               
                 AO25 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 573.4 
                 3.24 
                 SB 
               
               
                   
               
               
                 AO26 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 589.4 
                 3.32 
                 SB 
               
               
                   
               
               
                 AO27 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 589.4 
                 3.36 
                 SB 
               
               
                   
               
               
                 AO28 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 585.7 
                 3.76 
                 SB 
               
               
                   
               
               
                 AO29 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 556.3 
                 2.42 
                 SB 
               
               
                   
               
               
                 AO30 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 610.4 
                 3.28 
                 SB 
               
               
                   
               
               
                 AO31 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 572.3 
                 2.82 
                 SB 
               
               
                   
               
               
                 AO32 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 560.5 
                 2.9  
                 SB 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
             
               
                 TABLE 146 
               
               
                   
               
               
                 Ex. 
                   
                 obs MS 
                 tR 
                 Measurement 
               
               
                 No. 
                 —B 
                 [M + 1] 
                 (min) 
                 Method 
               
               
                   
               
             
            
               
                 AO33 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 576.2 
                 3.11 
                 SB 
               
               
                   
               
               
                 AO34 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 556.3 
                 2.51 
                 SB 
               
               
                   
               
               
                 AO35 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 569.5 
                 3.29 
                 SB 
               
               
                   
               
               
                 AO36 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 595.3 
                 3.36 
                 SB 
               
               
                   
               
               
                 AO37 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 542.3 
                 2.46 
                 SB 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
             
               
                 TABLE 147 
               
               
                   
               
               
                   
                   
                 obs MS 
                   
                 Measurement 
               
               
                 Ex. No. 
                 —B 
                 [M + 1] 
                 tR (min) 
                 Method 
               
               
                   
               
             
            
               
                 AP1 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 567.3 
                 3.63 
                 SB 
               
               
                   
               
               
                 AP2 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 567.3 
                 3.42 
                 SB 
               
               
                   
               
               
                 AP3 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 567.3 
                 3.65 
                 SB 
               
               
                   
               
               
                 AP4 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 567.3 
                 3.97 
                 SB 
               
               
                   
               
               
                 AP5 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 517.4 
                 2.92 
                 SB 
               
               
                   
               
               
                 AP6 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 524.4 
                 3.32 
                 SB 
               
               
                   
               
               
                 AP7 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 524.4 
                 3.36 
                 SB 
               
               
                   
               
               
                 AP8 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 500.3 
                 2.99 
                 SB 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
             
               
                 TABLE 148 
               
               
                   
               
               
                   
                   
                 obs MS 
                   
                 Measurement 
               
               
                 Ex. No. 
                 —B 
                 [M + 1] 
                 tR (min) 
                 Method 
               
               
                   
               
             
            
               
                 AP9 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 524.4 
                 3.40 
                 SB 
               
               
                   
               
            
           
         
       
     
     
       
         
         
             
             
         
       
     
     
       
         
           
               
               
               
               
               
             
               
                 TABLE 149 
               
               
                   
               
               
                   
                   
                 obs MS 
                   
                 Measurement 
               
               
                 Ex. No. 
                 —B 
                 [M + 1] 
                 tR (min) 
                 Method 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
               
            
               
                 AQ1 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 544.5 
                 3.58 
                 SA 
               
               
                   
               
               
                 AQ2 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 544.5 
                 3.68 
                 SA 
               
               
                   
               
               
                 AQ3 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 544.5 
                 3.65 
                 SA 
               
               
                   
               
               
                 AQ4 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 528.6 
                 3.48 
                 SA 
               
               
                   
               
               
                 AQ5 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 528.6 
                 3.51 
                 SA 
               
               
                   
               
               
                 AQ6 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 528.6 
                 3.5 
                 SA 
               
               
                   
               
               
                 AQ7 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 540.6 
                 3.43 
                 SA 
               
               
                   
               
               
                 AQ8 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 540.6 
                 3.48 
                 SA 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
             
               
                 TABLE 150 
               
               
                   
               
               
                   
                   
                 obs MS 
                   
                 Measurement 
               
               
                 Ex. No. 
                 —B 
                 [M + 1] 
                 tR (min) 
                 Method 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
               
            
               
                 AQ9 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 540.6 
                 3.47 
                 SA 
               
               
                   
               
               
                 AQ10 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 578.5 
                 3.72 
                 SA 
               
               
                   
               
               
                 AQ11 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 578.5 
                 3.81 
                 SA 
               
               
                   
               
               
                 AQ12 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 578.6 
                 3.83 
                 SA 
               
               
                   
               
               
                 AQ13 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 535.7 
                 3.39 
                 SA 
               
               
                   
               
               
                 AQ14 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 535.5 
                 3.39 
                 SA 
               
               
                   
               
               
                 AQ15 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 546.7 
                 3.6 
                 SA 
               
               
                   
               
               
                 AQ16 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 546.7 
                 3.57 
                 SA 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
             
               
                 TABLE 151 
               
               
                   
               
               
                 Ex. 
                   
                 obs MS 
                 tR 
                 Measurement 
               
               
                 No. 
                 —B 
                 [M + 1] 
                 (min) 
                 Method 
               
               
                   
               
             
            
               
                 AQ17 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 592.5 
                 3.85 
                 SA 
               
               
                   
               
               
                 AQ18 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 592.5 
                 3.92 
                 SA 
               
               
                   
               
               
                 AQ19 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 592.4 
                 3.9  
                 SA 
               
               
                   
               
               
                 AQ20 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 542.4 
                 3.61 
                 SA 
               
               
                   
               
               
                 AQ21 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 542.5 
                 3.6  
                 SA 
               
               
                   
               
               
                 AQ22 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 542.5 
                 3.6  
                 SA 
               
               
                   
               
               
                 AQ23 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 558.6 
                 3.7  
                 SA 
               
               
                   
               
               
                 AQ24 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 558.6 
                 3.77 
                 SA 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
             
               
                 TABLE 152 
               
               
                   
               
               
                 Ex. 
                   
                 obs MS 
                 tR 
                 Measurement 
               
               
                 No. 
                 —B 
                 [M + 1] 
                 (min) 
                 Method 
               
               
                   
               
             
            
               
                 AQ25 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 558.6 
                 3.76 
                 SA 
               
               
                   
               
               
                 AQ26 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 549.5 
                 3.49 
                 SA 
               
               
                   
               
               
                 AQ27 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 549.6 
                 3.46 
                 SA 
               
               
                   
               
               
                 AQ28 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 554.6 
                 3.6  
                 SA 
               
               
                   
               
               
                 AQ29 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 554.6 
                 3.54 
                 SA 
               
               
                   
               
               
                 AQ30 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 554.6 
                 3.53 
                 SA 
               
               
                   
               
               
                 AQ31 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 448.6 
                 3.03 
                 SA 
               
               
                   
               
               
                 AQ32 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 462.4 
                 3.2  
                 SA 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
             
               
                 TABLE 153 
               
               
                   
               
               
                 Ex. 
                   
                 obs MS 
                 tR 
                 Measurement 
               
               
                 No. 
                 —B 
                 [M + 1] 
                 (min) 
                 Method 
               
               
                   
               
             
            
               
                 AQ33 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 476.4 
                 3.49 
                 SA 
               
               
                   
               
               
                 AQ34 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 474.6 
                 3.28 
                 SA 
               
               
                   
               
               
                 AQ35 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 580.5 
                 3.61 
                 SA 
               
               
                   
               
               
                 AQ36 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 568.6 
                 3.74 
                 SA 
               
               
                   
               
               
                 AQ37 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 584.5 
                 3.9  
                 SA 
               
               
                   
               
               
                 AQ38 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 525.6 
                 2.75 
                 SA 
               
               
                   
               
               
                 AQ39 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 541.7 
                 3.3  
                 SA 
               
               
                   
               
               
                 AQ40 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 579.6 
                 3.59 
                 SA 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
             
               
                 TABLE 154 
               
               
                   
               
               
                   
                   
                 obs MS 
                   
                 Measurement 
               
               
                 Ex. No. 
                 —B 
                 [M + 1] 
                 tR (min) 
                 Method 
               
               
                   
               
             
            
               
                 AQ41 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 545.6 
                 3.43 
                 SA 
               
               
                   
               
               
                 AQ42 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 579.6 
                 3.62  
                 SA 
               
               
                   
               
               
                 AQ43 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 550.4 
                 3.76 
                 SA 
               
               
                   
               
               
                 AQ44 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 516.7 
                 3.43 
                 SA 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
             
               
                 TABLE 155 
               
               
                   
               
               
                   
                   
                 obs MS 
                   
                 Measurement 
               
               
                 Ex. No. 
                 —B 
                 [M + 1] 
                 tR (min) 
                 Method 
               
               
                   
               
             
            
               
                 AR1 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 580.4 
                 3.93 
                 SA 
               
               
                   
               
               
                 AR2 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 580.4 
                 4.05 
                 SA 
               
               
                   
               
               
                 AR3 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 580.4 
                 4.04 
                 SA 
               
               
                   
               
               
                 AR4 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 564.5 
                 3.83 
                 SA 
               
               
                   
               
               
                 AR5 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 564.6 
                 3.88 
                 SA 
               
               
                   
               
               
                 AR6 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 564.5 
                 3.88 
                 SA 
               
               
                   
               
               
                 AR7 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 576.4 
                 3.73 
                 SA 
               
               
                   
               
               
                 AR8 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 576.4 
                 3.87 
                 SA 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
             
               
                 TABLE 156 
               
               
                   
               
               
                   
                   
                 obs MS 
                 tR 
                 Measurement 
               
               
                 Ex. No. 
                 —B 
                 [M + 1] 
                 (min) 
                 Method 
               
               
                   
               
             
            
               
                 AR9 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 576.5 
                 3.84 
                 SA 
               
               
                   
               
               
                 AR10 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 614.3 
                 4.02 
                 SA 
               
               
                   
               
               
                 AR11 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 614.4 
                 4.14 
                 SA 
               
               
                   
               
               
                 AR12 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 614.4 
                 4.17 
                 SA 
               
               
                   
               
               
                 AR13 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 571.5 
                 3.76 
                 SA 
               
               
                   
               
               
                 AR14 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 571.5 
                 3.79 
                 SA 
               
               
                   
               
               
                 AR15 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 582.5 
                 3.92 
                 SA 
               
               
                   
               
               
                 AR16 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 582.5 
                 3.97 
                 SA 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
             
               
                 TABLE 157 
               
               
                   
               
               
                   
                   
                 obs MS 
                 tR 
                 Measurement 
               
               
                 Ex. No. 
                 —B 
                 [M + 1] 
                 (min) 
                 Method 
               
               
                   
               
             
            
               
                 AR17 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 582.2 
                 3.92 
                 SA 
               
               
                   
               
               
                 AR18 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 582.4 
                 3.99 
                 SA 
               
               
                   
               
               
                 AR19 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 582.4 
                 3.82 
                 SA 
               
               
                   
               
               
                 AR20 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 578.5 
                 3.82 
                 SA 
               
               
                   
               
               
                 AR21 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 594.4 
                 3.98 
                 SA 
               
               
                   
               
               
                 AR22 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 484.4 
                 3.23 
                 SA 
               
               
                   
               
               
                 AR23 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 498.6 
                 3.37 
                 SA 
               
               
                   
               
               
                 AR24 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 512.7 
                 3.52 
                 SA 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
             
               
                 TABLE 158 
               
               
                   
               
               
                   
                   
                 obs MS 
                   
                 Measurement 
               
               
                 Ex. No. 
                 —B 
                 [M + 1] 
                 tR (min) 
                 Method 
               
               
                   
               
             
            
               
                 AR25 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 510.7 
                 3.44 
                 SA 
               
               
                   
               
               
                 AR26 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 552.6 
                 3.69 
                 SA 
               
               
                   
               
               
                 AR27 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 547.6 
                 3.4 
                 SA 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
             
               
                 TABLE 159 
               
               
                   
               
               
                   
                   
                 obs MS 
                 tR 
                 Measurement 
               
               
                 Ex. No. 
                 —B 
                 [M + 1] 
                 (min) 
                 Method 
               
               
                   
               
             
            
               
                 AS1 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 543.4 
                 3.11 
                 SB 
               
               
                   
               
               
                 AS2 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 543.4 
                 3.24 
                 SB 
               
               
                   
               
               
                 AS3 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 543.4 
                 3.17 
                 SB 
               
               
                   
               
               
                 AS4 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 559.4 
                 3.27 
                 SB 
               
               
                   
               
               
                 AS5 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 559.4 
                 3.38 
                 SB 
               
               
                   
               
               
                 AS6 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 559.4 
                 3.34 
                 SB 
               
               
                   
               
               
                 AS7 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 555.5 
                 3.27 
                 SB 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
             
               
                 TABLE 160 
               
               
                   
               
               
                 Ex. 
                   
                 obs MS 
                 tR 
                 Measurement 
               
               
                 No. 
                 —B 
                 [M + 1] 
                 (min) 
                 Method 
               
               
                   
               
             
            
               
                 AS9 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 555.2 
                 3.07 
                 SB 
               
               
                   
               
               
                 AS10 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 550.43 
                 3.02 
                 SB 
               
               
                   
               
               
                 AS11 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 550.4 
                 3.15 
                 SB 
               
               
                   
               
               
                 AS12 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 550.4 
                 3.13 
                 SB 
               
               
                   
               
               
                 AS13 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 561.4 
                 3.15 
                 SB 
               
               
                   
               
               
                 AS14 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 561.4 
                 3.25 
                 SB 
               
               
                   
               
               
                 AS15 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 561.4 
                 3.03 
                 SB 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
             
               
                 TABLE 161 
               
               
                   
               
               
                   
                   
                   
                   
                 Measure- 
               
               
                 Ex. 
                   
                 obs MS 
                 tR 
                 ment 
               
               
                 No. 
                 —B 
                 [M + 1] 
                 (min) 
                 Method 
               
               
                   
               
             
            
               
                 AS17 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 561.4 
                 3.38 
                 SB 
               
               
                   
               
               
                 AS18 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 553.2 
                 3.24 
                 SB 
               
               
                   
               
               
                 AS19 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 553.5 
                 3.24 
                 SB 
               
               
                   
               
               
                 AS20 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 557.4 
                 3.15 
                 SB 
               
               
                   
               
               
                 AS21 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 557.4 
                 3.15 
                 SB 
               
               
                   
               
               
                 AS22 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 573.4 
                 3.3 
                 SB 
               
               
                   
               
               
                 AS23 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 569.5 
                 3.21 
                 SB 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
             
               
                 TABLE 162 
               
               
                   
               
               
                   
                   
                   
                   
                 Mea- 
               
               
                   
                   
                   
                   
                 sure- 
               
               
                 Ex. 
                   
                 obs MS 
                 tR 
                 ment 
               
               
                 No. 
                 —B 
                 [M + 1] 
                 (min) 
                 Method 
               
               
                   
               
             
            
               
                 AS25 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 557.4 
                 3.15 
                 SB 
               
               
                   
               
               
                 AS26 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 573.4 
                 3.27 
                 SB 
               
               
                   
               
               
                 AS27 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 573.4 
                 3.28 
                 SB 
               
               
                   
               
               
                 AS28 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 569.5 
                 3.17 
                 SB 
               
               
                   
               
               
                 AS29 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 540.4 
                 3.5 
                 SB 
               
               
                   
               
               
                 AS30 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 556.3 
                 2.78 
                 SB 
               
               
                   
               
               
                 AS31 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 544.3 
                 2.85 
                 SB 
               
               
                   
               
               
                 AS32 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 560.5 
                 3.14 
                 SB 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
             
               
                 TABLE 163 
               
               
                   
               
               
                   
                   
                 obs MS 
                 tR 
                 Measurement 
               
               
                 Ex. No. 
                 —B 
                 [M + 1] 
                 (min) 
                 Method 
               
               
                   
               
             
            
               
                 AS33 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 540.4 
                 3.47 
                 SB 
               
               
                   
               
               
                 AS34 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 553.2 
                 3.19 
                 SB 
               
               
                   
               
               
                 AS35 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 579.3 
                 3.29 
                 SB 
               
               
                   
               
               
                 AS36 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 526.4 
                 2.4 
                 SB 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
             
               
                 TABLE 164 
               
               
                   
               
               
                   
                   
                 obs MS 
                   
                 Measurement 
               
               
                 Ex. No. 
                 —B 
                 [M + 1] 
                 tR (min) 
                 Method 
               
               
                   
               
             
            
               
                 AT1 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 551.3 
                 3.55 
                 SB 
               
               
                   
               
               
                 AT2 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 508.4 
                 3.19 
                 SB 
               
               
                   
               
               
                 AT3 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 551.3 
                 3.86 
                 SB 
               
               
                   
               
               
                 AT4 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 508.4 
                 2.92 
                 SB 
               
               
                   
               
               
                 AT5 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 551.3 
                 3.30 
                 SB 
               
               
                   
               
               
                 AT6 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 508.4 
                 3.21 
                 SB 
               
               
                   
               
               
                 AT7 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 551.3 
                 3.21 
                 SB 
               
               
                   
               
               
                 AT8 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 508.4 
                 3.32 
                 SB 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
             
               
                 TABLE 165 
               
               
                   
               
               
                   
                   
                 obs MS 
                   
                 Measurement 
               
               
                 Ex. No. 
                 —B 
                 [M + 1] 
                 tR (min) 
                 Method 
               
               
                   
               
             
            
               
                 AT9 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 501.4 
                 2.82 
                 SB 
               
               
                   
               
               
                 AT10 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 514.6 
                 2.36 
                 SB 
               
               
                   
               
               
                 AT11 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 484.6 
                 2.90 
                 SB 
               
               
                   
               
            
           
         
       
     
     
       
         
         
             
             
         
       
     
     
       
         
           
               
               
               
               
               
             
               
                 TABLE 166 
               
               
                   
               
               
                 Ex. 
                   
                 obs MS 
                   
                 Measurement 
               
               
                 No. 
                 —B 
                 [M + 1] 
                 tR (min) 
                 Method 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
               
            
               
                 AU1 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 544.4 
                 3.58 
                 SA 
               
               
                   
               
               
                 AU2 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 544.6 
                 3.68 
                 SA 
               
               
                   
               
               
                 AU3 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 544.5 
                 3.67 
                 SA 
               
               
                   
               
               
                 AU4 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 528.6 
                 3.5 
                 SA 
               
               
                   
               
               
                 AU5 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 528.6 
                 3.53 
                 SA 
               
               
                   
               
               
                 AU6 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 528.6 
                 3.51 
                 SA 
               
               
                   
               
               
                 AU7 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 540.6 
                 3.44  
                 SA 
               
               
                   
               
               
                 AU8 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 540.6 
                 3.49 
                 SA 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
             
               
                 TABLE 167 
               
               
                   
               
               
                   
                   
                 obs MS 
                 tR 
                 Measurement 
               
               
                 Ex. No. 
                 —B 
                 [M + 1] 
                 (min) 
                 Method 
               
               
                   
               
             
            
               
                 AU9 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 540.6 
                 3.48 
                 SA 
               
               
                   
               
               
                 AU10 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 578.5 
                 3.72 
                 SA 
               
               
                   
               
               
                 AU11 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 578.5 
                 3.82 
                 SA 
               
               
                   
               
               
                 AU12 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 578.5 
                 3.83 
                 SA 
               
               
                   
               
               
                 AU13 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 535.7 
                 3.4 
                 SA 
               
               
                   
               
               
                 AU14 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 535.6 
                 3.39 
                 SA 
               
               
                   
               
               
                 AU15 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 546.7 
                 3.58 
                 SA 
               
               
                   
               
               
                 AU16 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 546.7 
                 3.76 
                 SA 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
             
               
                 TABLE 168 
               
               
                   
               
               
                   
                   
                 obs MS 
                 tR 
                 Measurement 
               
               
                 Ex. No. 
                 —B 
                 [M + 1] 
                 (min) 
                 Method 
               
               
                   
               
             
            
               
                 AU17 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 546.7 
                 3.59 
                 SA 
               
               
                   
               
               
                 AU18 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 592.5 
                 3.85 
                 SA 
               
               
                   
               
               
                 AU19 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 592.5 
                 3.91 
                 SA 
               
               
                   
               
               
                 AU20 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 592.5 
                 3.87 
                 SA 
               
               
                   
               
               
                 AU21 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 542.5 
                 3.61 
                 SA 
               
               
                   
               
               
                 AU22 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 542.5 
                 3.62 
                 SA 
               
               
                   
               
               
                 AU23 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 542.5 
                 3.6 
                 SA 
               
               
                   
               
               
                 AU24 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 558.6 
                 3.88 
                 SA 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
             
               
                 TABLE 169 
               
               
                   
               
               
                 Ex. 
                   
                 obs MS 
                 tR 
                 Measurement 
               
               
                 No. 
                 —B 
                 [M + 1] 
                 (min) 
                 Method 
               
               
                   
               
             
            
               
                 AU25 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 558.6 
                 3.77 
                 SA 
               
               
                   
               
               
                 AU26 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 558.5 
                 3.76 
                 SA 
               
               
                   
               
               
                 AU27 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 549.7 
                 3.47 
                 SA 
               
               
                   
               
               
                 AU28 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 549.6 
                 3.45 
                 SA 
               
               
                   
               
               
                 AU29 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 554.6 
                 3.61 
                 SA 
               
               
                   
               
               
                 AU30 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 554.6 
                 3.55 
                 SA 
               
               
                   
               
               
                 AU31 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 554.6 
                 3.53 
                 SA 
               
               
                   
               
               
                 AU32 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 448.6 
                 3.05 
                 SA 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
             
               
                 TABLE 170 
               
               
                   
               
               
                 Ex. 
                   
                 obs MS 
                 tR 
                 Measurement 
               
               
                 No. 
                 —B 
                 [M + 1] 
                 (min) 
                 Method 
               
               
                   
               
             
            
               
                 AU33 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 462.5 
                 3.21 
                 SA 
               
               
                   
               
               
                 AU34 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 476.4 
                 3.37 
                 SA 
               
               
                   
               
               
                 AU35 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 474.4 
                 3.28 
                 SA 
               
               
                   
               
               
                 AU36 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 580.5 
                 3.61 
                 SA 
               
               
                   
               
               
                 AU37 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 584.5 
                 3.9 
                 SA 
               
               
                   
               
               
                 AU38 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 525.7 
                 2.76 
                 SA 
               
               
                   
               
               
                 AU39 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 541.5 
                 3.3 
                 SA 
               
               
                   
               
               
                 AU40 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 579.6 
                 3.55 
                 SA 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
             
               
                 TABLE 171 
               
               
                   
               
               
                   
                   
                 obs MS 
                   
                 Measurement 
               
               
                 Ex. No. 
                 —B 
                 [M + 1] 
                 tR (min) 
                 Method 
               
               
                   
               
             
            
               
                 AU41 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 545.6 
                 3.43 
                 SA 
               
               
                   
               
               
                 AU42 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 579.6 
                 3.63 
                 SA 
               
               
                   
               
               
                 AU43 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 550.5 
                 3.75 
                 SA 
               
               
                   
               
               
                 AU44 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 516.7 
                 3.42 
                 SA 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
             
               
                 TABLE 172 
               
               
                   
               
               
                   
                   
                 obs MS 
                   
                 Measurement 
               
               
                 Ex. No. 
                 —B 
                 [M + 1] 
                 tR (min) 
                 Method 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
               
            
               
                 AV1 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 580.4 
                 3.94 
                 SA 
               
               
                   
               
               
                 AV2 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 580.4 
                 4.07 
                 SA 
               
               
                   
               
               
                 AV3 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 580.4 
                 4.06 
                 SA 
               
               
                   
               
               
                 AV4 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 564.4 
                 3.83 
                 SA 
               
               
                   
               
               
                 AV5 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 564.4 
                 3.9 
                 SA 
               
               
                   
               
               
                 AV6 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 564.6  
                 3.88 
                 SA 
               
               
                   
               
               
                 AV7 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 576.5 
                 3.74 
                 SA 
               
               
                   
               
               
                 AV8 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 576.5 
                 3.88 
                 SA 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
             
               
                 TABLE 173 
               
               
                   
               
               
                   
                   
                 obs MS 
                   
                 Measurement 
               
               
                 Ex. No. 
                 —B 
                 [M + 1] 
                 tR (min) 
                 Method 
               
               
                   
               
             
            
               
                 AV9  
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 576.5 
                 3.84 
                 SA 
               
               
                   
               
               
                 AV10 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 614.4 
                 4.03 
                 SA 
               
               
                   
               
               
                 AV11 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 614.3 
                 4.14 
                 SA 
               
               
                   
               
               
                 AV12 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 614.4 
                 4.17 
                 SA 
               
               
                   
               
               
                 AV13 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 571.5 
                 3.71 
                 SA 
               
               
                   
               
               
                 AV14 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 571.5 
                 3.76 
                 SA 
               
               
                   
               
               
                 AV15 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 571.5 
                 3.79 
                 SA 
               
               
                   
               
               
                 AV16 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 582.3 
                 3.92 
                 SA 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
             
               
                 TABLE 174 
               
               
                   
               
               
                 Ex.  
                   
                 obs MS 
                   
                 Measurement 
               
               
                 No. 
                 —B 
                 [M + 1] 
                 tR (min) 
                 Method 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
               
            
               
                 AV17 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 582.3 
                 3.98 
                 SA 
               
               
                   
               
               
                 AV18 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 582.3 
                 3.93 
                 SA 
               
               
                   
               
               
                 AV19 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 582.4 
                 4.01 
                 SA 
               
               
                   
               
               
                 AV20 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 582.3 
                 3.97 
                 SA 
               
               
                   
               
               
                 AV21 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 578.5 
                 3.83 
                 SA 
               
               
                   
               
               
                 AV22 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 594.4 
                 4 
                 SA 
               
               
                   
               
               
                 AV23 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 484.5 
                 3.4 
                 SA 
               
               
                   
               
               
                 AV24 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 498.6 
                 3.37 
                 SA 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
             
               
                 TABLE 175 
               
               
                   
               
               
                   
                   
                 obs MS 
                   
                 Measurement 
               
               
                 Ex. No. 
                 —B 
                 [M + 1] 
                 tR (min) 
                 Method 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
               
            
               
                 AV25 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 512.7 
                 3.51 
                 SA 
               
               
                   
               
               
                 AV26 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 510.5 
                 3.46 
                 SA 
               
               
                   
               
               
                 AV27 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 552.4 
                 3.7 
                 SA 
               
               
                   
               
               
                 AV28 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 547.6 
                 3.4 
                 SA 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
             
               
                 TABLE 176 
               
               
                   
               
               
                   
                   
                 obs MS 
                   
                 Measurement 
               
               
                 Ex. No. 
                 —B 
                 [M + 1] 
                 tR (min) 
                 Method 
               
               
                   
               
             
            
               
                 AW1 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 543.4 
                 3.11 
                 SB 
               
               
                   
               
               
                 AW2 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 543.4 
                 3.24 
                 SB 
               
               
                   
               
               
                 AW3 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 543.4 
                 3.15 
                 SB 
               
               
                   
               
               
                 AW4 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 559.6 
                 3.74 
                 SA 
               
               
                   
               
               
                 AW5 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 559.5 
                 3.81 
                 SA 
               
               
                   
               
               
                 AW6 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 559.5 
                 3.79 
                 SA 
               
               
                   
               
               
                 AW7 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 555.2 
                 3.21 
                 SB 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
             
               
                 TABLE 177 
               
               
                   
               
               
                   
                   
                   
                   
                 Measure- 
               
               
                 Ex. 
                   
                 obs MS 
                 tR 
                 ment 
               
               
                 No. 
                 —B 
                 [M + 1] 
                 (min) 
                 Method 
               
               
                   
               
             
            
               
                 AW9  
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 555.5 
                 3.07 
                 SB 
               
               
                   
               
               
                 AW10 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 550.7 
                 3.08 
                 SA 
               
               
                   
               
               
                 AW11 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 550.7 
                 3.18 
                 SA 
               
               
                   
               
               
                 AW12 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 550.7 
                 3.69 
                 SA 
               
               
                   
               
               
                 AW13 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 561.7 
                 3.58 
                 SA 
               
               
                   
               
               
                 AW14 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 561.4 
                 3.32 
                 SA 
               
               
                   
               
               
                 AW15 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 561.4 
                 3.13 
                 SB 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
             
               
                 TABLE 178 
               
               
                   
               
               
                   
                   
                   
                   
                 Mea- 
               
               
                   
                   
                   
                   
                 sure- 
               
               
                   
                   
                   
                   
                 ment 
               
               
                 Ex. 
                   
                 obs MS 
                 tR 
                 Meth- 
               
               
                 No. 
                 —B 
                 [M + 1] 
                 (min) 
                 od 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
               
            
               
                 AW17 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 561.7 
                 3.96 
                 SB 
               
               
                   
               
               
                 AW18 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 553.8 
                 3.9 
                 SB 
               
               
                   
               
               
                 AW19 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 553.5 
                 3.86 
                 SB 
               
               
                   
               
               
                 AW20 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 557.7 
                 3.72 
                 SB 
               
               
                   
               
               
                 AW21 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 557.7 
                 3.76 
                 SB 
               
               
                   
               
               
                 AW22 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 573.4 
                 3.28 
                 SB 
               
               
                   
               
               
                 AW23 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 569.5 
                 3.15 
                 SB 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
             
               
                 TABLE 179 
               
               
                   
               
               
                   
                   
                   
                   
                 Mea- 
               
               
                   
                   
                 obs 
                   
                 sure- 
               
               
                   
                   
                 MS 
                   
                 ment 
               
               
                 Ex. 
                   
                 [M + 
                 tR 
                 Meth- 
               
               
                 No. 
                 —B 
                 1] 
                 (min) 
                 od 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
               
            
               
                 AW25 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 569.5 
                 3.1 
                 SB 
               
               
                   
               
               
                 AW26 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 557.4 
                 3.23 
                 SB 
               
               
                   
               
               
                 AW27 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 573.4 
                 3.26 
                 SB 
               
               
                   
               
               
                 AW28 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 573.4 
                 3.29 
                 SB 
               
               
                   
               
               
                 AW29 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 540.4 
                 2.4 
                 SB 
               
               
                   
               
               
                 AW30 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 594.4 
                 3.21 
                 SB 
               
               
                   
               
               
                 AW31 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 556.3 
                 2.73 
                 SB 
               
               
                   
               
               
                 AW32 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 544.6 
                 2.86 
                 SB 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
             
               
                 TABLE 180 
               
               
                   
               
               
                   
                   
                 obs MS 
                 tR 
                 Measurement 
               
               
                 Ex. No. 
                 —B 
                 [M + 1] 
                 (min) 
                 Method 
               
               
                   
               
             
            
               
                 AW33 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 560.5 
                 3.05 
                 SB 
               
               
                   
               
               
                 AW34 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 540.4 
                 2.44 
                 SB 
               
               
                   
               
               
                 AW35 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 579.3 
                 3.34 
                 SB 
               
               
                   
               
               
                 AW36 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 526.4 
                 2.38 
                 SB 
               
               
                   
               
               
                 AW37 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 553.2 
                 3.21 
                 SB 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
             
               
                 TABLE 181 
               
               
                   
               
               
                   
                   
                 obs MS 
                   
                 Measurement 
               
               
                 Ex. No. 
                 —B 
                 [M + 1] 
                 tR (min) 
                 Method 
               
               
                   
               
             
            
               
                 AX1 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 551.3 
                 3.55 
                 SB 
               
               
                   
               
               
                 AX2 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 551.3 
                 3.30 
                 SB 
               
               
                   
               
               
                 AX3 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 551.3 
                 3.54 
                 SB 
               
               
                   
               
               
                 AX4 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 551.3 
                 3.84 
                 SB 
               
               
                   
               
               
                 AX5 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 501.4 
                 2.82 
                 SB 
               
               
                   
               
               
                 AX6 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 508.4 
                 3.19 
                 SB 
               
               
                   
               
               
                 AX7 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 508.4 
                 3.20 
                 SB 
               
               
                   
               
               
                 AX8 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 484.6 
                 2.90 
                 SB 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
             
               
                 TABLE 182 
               
               
                   
               
               
                   
                   
                 obs MS 
                   
                 Measurement 
               
               
                 Ex. No. 
                 —B 
                 [M + 1] 
                 tR (min) 
                 Method 
               
               
                   
               
             
            
               
                 AX9 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 508.4 
                 3.30 
                 SB 
               
               
                   
               
            
           
         
       
     
     Comparative Example 1A 
     
       
         
         
             
             
         
       
     
     To a solution of Compound I (6.91 g) in 99.5% ethanol (100 mL) was added sodium bicarbonate (3.31 g), and then thereto was added ethyl bromopyruvate (3.0 mL) and then the mixture was stirred at 80° C. After 4 hours, thereto was added acetic acid (50 mL), and the mixture was stirred at 120° C. The mixture was stirred overnight, and then cooled to room temperature and concentrated in vacuo. To the residue was added saturated sodium bicarbonate water, and the mixture was extracted with ethyl acetate. The organic layer was dried over sodium sulfate and concentrated in vacuo. The residue was purified by silica gel chromatography (eluent: hexane/ethyl acetate=1/1 to chloroform/methanol=10/1) to give the titled Compound II (2.48 g) (30.4% yields). 
     Comparative Example 1B 
     
       
         
         
             
             
         
       
     
     To a solution of Compound I (6.91 g) in 99.5% ethanol (100 mL) was added sodium bicarbonate (3.31 g). Then, thereto was added ethyl bromopyruvate (3.0 mL), and then the mixture was stirred at 80° C. After 4 hours, thereto was added acetic acid (50 mL), and the mixture was stirred at 120° C. The mixture was stirred overnight, and then cooled to room temperature and concentrated in vacuo. To the residue was added saturated sodium bicarbonate water, and the mixture was extracted with ethyl acetate. The organic layer was dried over sodium sulfate and concentrated in vacuo. The residue was purified by silica gel chromatography (eluent: hexane/ethyl acetate=1/1 to chloroform/methanol=10/1) to give the titled Compound II (2.48 g) (30.4% yields). 
     Comparative Example 2 
     
       
         
         
             
             
         
       
     
     To an ice-cooled mixed solution of Compound I (24.9 g), sodium bicarbonate (9.66 g) and 95% ethanol (350 mL) was added ethyl bromopyruvate (11.9 mL). The mixture was stirred at 80° C. for 4 hours, and the reaction solution was evaporated to concentrate in vacuo. To the residue was added acetic acid (150 mL), and the mixture was stirred at 130° C. for 18 hours and then concentrated in vacuo. To the residue was added saturated sodium bicarbonate water, and the mixture was extracted with ethyl acetate. The organic layer was dried over sodium sulfate and concentrated in vacuo. The residue was purified by silica gel chromatography (eluent: hexane/ethyl acetate=1/1) to give the titled Compound II (14.6 g) (49% yields). 
     Comparative Example 3 
     
       
         
         
             
             
         
       
     
     To an ice-cooled solution of Compound I (16.44 g) in 99.5% ethanol (125 mL) was added ethyl bromopyruvate (7.83 mL), and then the mixture was stirred at 80° C. After 4 hours, the reaction solution was evaporated to concentrate in vacuo. To the residue was added acetic acid (150 mL), and the mixture was stirred at 130° C. for 18 hours and then concentrated in vacuo. To the residue was added saturated sodium bicarbonate water, and the mixture was extracted with ethyl acetate. The organic layer was dried over sodium sulfate and concentrated in vacuo. The residue was purified by silica gel chromatography (eluent: hexane/ethyl acetate=1/1) to give the titled Compound II (1.43 g) (7% yields). 
     Experiment 1 (Preparation of Human 11βHSD1 Enzyme Source) 
     A sequence containing ORF of human 11βHSD1 gene (GenBank Accession No. BC012593) was amplified according to PCR technique which was one of conventional methods, and digested by a restriction enzyme BamHI/XhoI. 2 kb of DNA fragments obtained from agarose gels were inserted into pCMV-Tag 2B plasmids (Stratagene) according to a conventional method. The plasmids prepared in  Escherichia coli  in large amounts were transformed into CHO-K1 cells, and then cells stably expressing human 11βHSD1 genes were selected by medium containing 400 μg/ml G-418 solution (GIBCO, Inc.) containing media. The resulting stably expressing cells were incubated up to −90% confluent in F-12 medium (Nacalai Tesque, Inc.) containing 10% charcoal-dextran treated fetal bovine serum (Hyclone), 1% penicillin-streptomycin (Nacalai Tesque, Inc.) and 400 μg/ml G-418. The resultant cells were treated by tripsin, and the obtained cells were suspended in the above media (1 L) and seeded in cell stack 10 chamber (Corning) in total amounts. The mixture was incubated in CO 2  incubator (5% CO 2 , 37° C.) for 4-5 days, and then treated by tripsin. Total amounts of the obtained cells were washed with PBS buffer (GIBCO, Inc.), and stored at −80° C. The cells were suspended in 8 ml of buffer (50 mM HEPES pH7.3, 5% glycerol, 1 mM EDTA, protease inhibitor cocktail (Roche)), and then disrupted. The resulting solution was centrifuged at 1,500 rpm for 10 minutes, and then the supernatant was ultracentrifuged at 100,000 g for 1 hour. The precipitate after the ultracentrifugation was collected and suspended in buffer (50 mM HEPES pH7.3, 5% glycerol, 1 mM EDTA), and then dispensed to store at −80° C. The resulting enzyme fractions were used as human 11βHSD1 enzyme fractions in the following Experiments. 
     Experiment 2 (Measurement of Human 11βHSD1 Inhibitory Activity) 
     A test compound and cortisone (Sigma) was diluted with buffer (50 mM HEPES pH7.3, 150 mM NaCl, 1 mM EDTA) to prepare a substrate solution containing a test compound (50 mM HEPES pH7.3, 150 mM NaCl, 1 mM EDTA, 1 mM NADPH, 20 nM cortisone) (2% DMSO solution), and the solution was added to 384-well low-volume plate (manufactured by Greiner, No. 3782086) in 4 μl/well. Then, human 11βHSD1 enzyme fractions obtained in Experiment 1 were diluted with buffer (50 mM HEPES pH7.3, 150 mM NaCl, 1 mM EDTA, 5% glycerol) to be 60-100 μg/ml of post-assay concentrations. Human 11βHSD1 enzyme fractions after the dilution was added to each well in 4 μl/well and gently stirred, and then spun down to react at 37° C. for 2 hours. After the enzyme reaction, the produced cortisol was detected by Homogeneous time-resolved fluorescence (HTRF) to determine enzyme inhibitory activities. Then, thereto were added XL-665 labeled cortisol (or d2-labeled cortisol) containing 400 μM carbenoxolone (Sigma) and cryptate-labeled cortisol antibody (Cisbio International) in 4 μl/well each, and the mixture was gently stirred, and then spun down to store at room temperature for 2 or more hours. A fluorescence intensity was determined by 2120 EnVision® Multilabel counter (PerkinElmer) to calculate enzyme inhibitory activities from 2 wavelengths of fluorescence intensity ratios (665 nm/620 nm). 
     Each inhibitory activity (%) of each test compound was calculated from the average value (%) of inhibitory activities of 4 wells under the same condition. An inhibition rate in a well wherein DMSO was added instead of a test compound was 0% and an inhibition rate in a well without human 11βHSD1 enzyme fractions was 100%. A concentration (IC 50  value) of a test compound required to inhibit 50% of human 11βHSD1 was calculated. 
     The result was shown in Table 1. 
     
       
         
           
               
               
               
             
               
                   
                 TABLE 183 
               
               
                   
                   
               
               
                   
                 Example No. 
                 IC 50  (nM) 
               
               
                   
                   
               
             
            
               
                   
               
            
           
           
               
               
               
            
               
                 1 
                 11 
                 32 
               
               
                 2 
                 15 
                 39 
               
               
                 3 
                 19 
                 25 
               
               
                   
               
            
           
         
       
     
     Experiment 3 (Inhibitory Activity Assay for Cortisone Reducing Activity of Cultured Human Adipocytes) 
     Normal human proadipocytes (HPrAD-vis, Cambrex) were inoculated on 48 well plate, and differentiated according to a protocol attached to a kit. Media for cells on 9-11th day of differentiation were changed to 0.2 ml of D-MEM media (GIBCO, Inc.) containing 100 nM [1,2- 3 H] cortisone (1 μCi/well, Muromati Yakuhin), 0.5% DMSO, test compound (DMSO only for test compound-addition districts and test compound additive-free districts). After incubation at 37° C. for 3 hours, all media were collected. As background districts, cell additive-free media were used. Media were mixed with ethyl acetate (0.1 ml) in Eppendorf tube. The mixture was vortexed, and then centrifuged at 5,000 rpm×1 minute at room temperature to separate ethyl acetate (upper layer). Ethyl acetate (10 μl) was spotted on aluminum plate for thin-layer chromatography (silica gel 60 angstrom, Merck, referred to as TLC plate hereinafter). To a sealed vessel was added chloroform/methanol (90:10, v/v) as an eluent, and TLC plate was developed and then dried at room temperature. To the dried TLC plate was exposed an imaging plate (TR-2040, FUJIFILM) over 16 or more hours. After exposure, the imaging plate was analyzed by Bioimage analyzer (BAS2500, FUJIFILM), and [ 3 H] radioactivity of the spot corresponding to cortisol on TLC plate was determined Inhibitory activities of cortisone reducing activities of test compounds were calculated as below. 
       (Inhibitory activity (%))=100×((Test compound additive-free districts)−(Test compound-addition districts))/((Test compound additive-free districts)−(Background districts))
 
     IC 50  values were calculated by a linear regression of logarithmic values of analyte concentrations and inhibitory activity values using 2-point data wherein inhibitory activities indicated values around 50%. IC 50  values for human adipocyte cortisone reducing activities of the inventive compound usually exist within the range of 0.01-1000 nM. IC 50  values for human adipocyte cortisone reducing activities of the following inventive compounds were determined 
     
       
         
           
               
               
               
             
               
                   
                 TABLE 184 
               
               
                   
                   
               
               
                   
                 Example No. 
                 IC 50  (nM) 
               
               
                   
                   
               
             
            
               
                   
               
            
           
           
               
               
               
            
               
                 1 
                 8 
                 8.7 
               
               
                 2 
                 22 
                 1.8 
               
               
                 3 
                 65 
                 9.1 
               
               
                 4 
                 66 
                 0.3 
               
               
                 5 
                 70 
                 39 
               
               
                 6 
                 82 
                 43 
               
               
                 7 
                 129 
                 3.5 
               
               
                 8 
                 153 
                 22 
               
               
                 9 
                 160 
                 5.6 
               
               
                 10 
                 166 
                 6.4 
               
               
                 11 
                 K16 
                 11 
               
               
                 12 
                 I26 
                 3.1 
               
               
                 13 
                 V18 
                 21 
               
               
                 14 
                 AN2 
                 6.7 
               
               
                   
               
            
           
         
       
     
     According to the experiment of Table 2, the inventive compound group is expected to inhibit an 11βHSD1 activity and cortisol production in the target organ human adipocyte. 
     Experiment 4 (Inhibitory Activity Assay for Cortisone Reducing Activity of Mouse Primary Adipocytes) 
     Adipose tissues (referred to as visceral fat tissues hereinafter) adhered around mesenteries and testicles of 10 of 9-11 week-old ICR male mice (Japan SLC, Inc.) were soaked in phosphate buffer (0.20 g/L KCl, 0.20 g/L KH 2 PO 4 , 8.00 g/L NaCl, 2.16 g/L Na 2 HPO 4 .7H 2 O, 100 unit/ml penicillin (GIBCO, Inc.), 100 μg/ml streptomycin (GIBCO, Inc.), 250 ng/ml amphotericin (GIBCO, Inc.)) (about 100 ml) and washed at room temperature. 
     The visceral fat tissues removed as above were cut out in about 5×5 mm by scissors in Dulbecco&#39;s Modified Eagle Media (containing 4.5 g/L D-glucose and 584 mg/L L-glutamine, GIBCO, Inc.) (about 50 ml) wherein collagenase (type II, Sigma), penicillin (GIBCO, Inc.), streptomycin (GIBCO, Inc.) and amphotericin (GIBCO, Inc.) were added until the final concentration of 1 mg/ml, 100 unit/ml, 100 μg/ml and 250 ng/ml each. Then, the tissues were shaken at 37° C. for 30 minutes (about 170 rpm) and filtered through nylon mesh (80S [250 μm mesh], SANSHIN INDUSTRIAL CO., LTD.) to give a filtrate (cell suspension). The filtrate was centrifuged at room temperature at 1800 rpm for 5 minutes, and then the liquid layer was gently removed by decantation to give a precipitate. The precipitate was suspended in Dulbecco&#39;s Modified Eagle Media (containing 4.5 g/L D-glucose and 584 mg/L L-glutamine, GIBCO, Inc., also referred to as FBS-containing media hereinafter) (30 ml) wherein fetal bovine serum (referred to as FBS hereinafter) (GIBCO, Inc.), ascorbic acid (Wako Pure Chemical Industries, Ltd.), penicillin (GIBCO, Inc.), streptomycin (GIBCO, Inc.) and amphotericin (GIBCO, Inc.) were added until the final concentration of 10%, 200 μM, 100 unit/ml, 100 μg/ml and 250 ng/ml each, and the suspension was filtered through nylon mesh (420S [25 μm mesh], SANSHIN INDUSTRIAL CO., LTD.). The filtrate was collected and centrifuged at room temperature at 1800 rpm for 5 minutes, and then the liquid layer was gently removed by decantation and the precipitate was suspended again in FBS-containing media (30 ml). The similar treatment of centrifugation, removal of liquid layer and suspension in FBS-containing media was further carried out twice for the resulting suspension to prepare the suspension (90 ml). The suspension was dispensed in flasks for cell incubation (T150 for adhered cells, IWAKI GLASS) by 30 ml each, and incubated at 37° C. in the presence of 5% CO 2 . 5-6 hours after starting incubation, media were removed and flask walls were washed with the phosphate buffer (15 ml). The washing was removed and the washing operation was carried out again. Then, the phosphate buffer was removed, and FBS-containing media (30 ml) was added to flasks and incubated at 37° C. in the presence of 5% CO 2 . 1 or 2 days after starting incubation, media were removed and flask walls were washed with the phosphate buffer (15 ml) once. Then, to the flask was added tripsin-ethylene diamine tetracetic acid (referred to as tripsin-EDTA hereinafter) solution (0.05% tripsin, 0.53 mM EDTA.4Na, GIBCO, Inc.) so that cells were soaked, and the mixture was incubated at 37° C. for 5 minutes. Then, thereto were added FBS-containing media in about tenfold amounts of tripsin-EDTA solution, and the cell suspension was obtained. 
     The cell suspension was diluted by the addition of FBS-containing media so that the number of cells in the cell suspension was determined by a counting chamber to be 1.4×10 5  cells/ml. The resulting diluent was dispensed in 48 well plate (for incubation of adherent cells, IWAKI GLASS) by 300 μl/well each, and incubated at 37° C. for 1-2 days in the presence of 5% CO 2 . Media were removed from each well of 48 well plate, and FBS-containing media (300 μl) containing 10 μg/ml insulin (Sigma), 0.25 μM dexamethazone (Wako Pure Chemical Industries, Ltd.), 0.5 mM 3-isobutyl-1-methyl-xanthin (Sigma) and 5 μM 15-deoxy-Δ 12,14 -prostaglandin J 2  (Cayman) were added to each well and incubated at 37° C. for 3 days in the presence of 5% CO 2 . Then, media in each well were removed, and FBS-containing media (300 μl) containing 10 μg/ml insulin and 5 μM 15-deoxy-Δ 12,14 -prostaglandin J 2  were added to each well and incubated for 2 days. Further, media in each well were removed, and FBS-containing media (300 μl) containing 10 μg/ml insulin and 5 μM 15-deoxy-Δ 12,14 -prostaglandin J 2  were added to each well and incubated for 2 days. 
     Media for adipocyte as differentiated above were changed to 0.2 ml of D-MEM media (GIBCO, Inc.) containing 100 nM [1,2- 3 H] cortisone (1 μCi/well, Muromati Yakuhin), 0.5% DMSO, test compound (DMSO only for test compound-addition districts and test compound additive-free districts). After incubation at 37° C. for 3 hours, all media were removed. As background districts, cell additive-free media were used. Media were combined with ethyl acetate (0.1 ml) in Eppendorf tube. The mixture was vortexed, and then centrifuged at 5,000 rpm×1 minute at room temperature to separate ethyl acetate (upper layer). Ethyl acetate (10 μl) was spotted on aluminum plate for thin-layer chromatography (silica gel 60 angstrom, Merck, referred to as TLC plate hereinafter). To a sealed vessel was added chloroform/methanol (90:10, v/v) as an eluent, and TLC plate was developed and then dried at room temperature. To the dried TLC plate was exposured an imaging plate (TR-2040, FUJIFILM) over 16 or more hours. After exposure, the imaging plate was analyzed by Bioimage analyzer (BAS2500, FUJIFILM), and [ 3 H] radioactivity of the spot corresponding to cortisol on TLC plate was determined Inhibitory activities of cortisone reducing activities of test compounds were calculated as below. 
       (Inhibitory activity (%))=100×((Test compound additive-free districts)−(Test compound-addition districts))/((Test compound additive-free districts)−(Background districts))
 
     IC 50  values were calculated by a linear regression of logarithmic values of analyte concentrations and inhibitory activity values using 2-point data wherein inhibitory activities indicated values around 50%. IC 50  values for mouse adipocyte cortisone reducing activities of the inventive compound usually exist within the range of 0.01-1000 nM. IC 50  values for mouse adipocyte cortisone reducing activities of the following inventive compounds were determined. The results are shown below. 
     
       
         
           
               
               
               
             
               
                   
                 TABLE 185 
               
               
                   
                   
               
               
                   
                 Example No. 
                 IC 50  (nM) 
               
               
                   
                   
               
             
            
               
                   
               
            
           
           
               
               
               
            
               
                 1 
                 51 
                 5.6 
               
               
                 2 
                 62 
                 47 
               
               
                 3 
                 64 
                 2.4 
               
               
                 4 
                 66 
                 0.6 
               
               
                 5 
                 74 
                 4.0 
               
               
                 6 
                 93 
                 1.5 
               
               
                 7 
                 96 
                 55 
               
               
                 8 
                 169 
                 4 
               
               
                 9 
                 A41 
                 &lt;10 
               
               
                 10 
                 Y9  
                 4.2 
               
               
                   
               
            
           
         
       
     
     The inventive compound has good properties as a medicinal product. The properties include solubility which may be measured according to methods of Experiments 5-1 and 5-2 or other known methods. 
     Experiment 5-1 (Elution Method) 
     1.75% aqueous disodium hydrogen phosphate solution was mixed with 5.53% aqueous citric acid solution with monitoring by pH indicator to prepare isotonic buffer solutions of pH=7.4 and 6.0. A buffer of pH=1.2 (Pharmacopeia Solution 1) was prepared according to Pharmacopeia. Then, a standard solution was prepared. A test compound (about 1 mg) was precisely weighed in 10 ml measuring flask and dissolved in HPLC carrier (0.1% TFA water/acetonitrile=1/1) to prepare 100 μg/ml standard solution. An elution condition for a test compound was set by the standard solution in ODS column (ChemcoPack Quicksorb: 4.6 mmφ×150 mm, 5 μm) at 5-10 min. Detection was carried out by UV at both 254 and 230 nm of wavelengths. Quantification was carried out on the basis of the former detected data, and in case of a low sensitibity, the latter detected data was adopted. Dissolution and analysis were carried out as follows. A test compound (about 1 mg) was weighed in 1 ml glass sample tube, and thereto was added each pH of isotonic buffer solution (0.4 ml) by PIPETMAN® and the mixture was shaken at room temperature for 1.5 hours (Conditions: RECIPRO SHAKER SR-1N manufactured by TAITEC, Speed=8). Then, the solution was transferred to 1.5 ml Eppendorf tube, and centrifuged by a compact high-speed centrifuge at 15.000 rpm for 5 minutes to separate an insoluble. The supernatant was analyzed by HPLC without any purification to calculate a concentration (solubility) by area ratios with a standard solution. 
     Experiment 5-2 (Dimethylsulfoxide (Abbreviated as DMSO Hereinafter) Deposition Method) 
     1.75% aqueous disodium hydrogen phosphate solution was mixed with 5.53% aqueous citric acid solution with monitoring by pH indicator to prepare each isotonic buffer solution of pH=7.4. A buffer of pH=1.2 (Pharmacopeia Solution 1) was prepared according to Pharmacopeia. Then, a standard solution was prepared. A test compound (2 μL, 10 mM DMSO solution) was dispensed in 96 well plate and diluted with 50% acetonitrile (198 μL). A HPLC analysis condition was determined by the standard solution. The analysis was carried out under HPLC (Column: ACQUITY HPLC BEH® C18 1.7 μm 2.1 mm×50 mm, Guard column: VanGuard® Pre-column 2.1×5 mm, Mobile phase: solution A; 0.1% TFA aqueous solution, solution B; 0.1% TFA acetonitrile solution, Gradient: 0.00 min-solution B: 5%, 2.00 min-solution B: 100%, 2.71 min-solution B: 5%, 3.50 min-stop, Column temperature: 40° C., flow rate: 0.4 mL/min, Detection wavelength: 254 or 230 nm, Sample injection: 5 μL), and a measurement wavelength and injection amounts of analysis were determined by the result. Dissolution and analysis were carried out as follows. Samples (10 mM DMSO solution) were dispensed in four Utube on 96 well rack by 15 μL, and evaporate to dryness by centrifugal evaporation at 40° C. for 90 minutes. Thereto was added DMSO (3 μL) to dissolve again, and then buffers of pH7.4 and 1.2 were added to 2 wells each in 300 μL each. After shaking at 25° C. at 110 rpm for 90 minutes, the mixture let stand for 16-20 hours and centrifuged at 2000 g for 15 minutes to separate an insoluble and collect a supernatant (100 μL) in 96 well plate. A test compound (2 μL, 10 mM DMSO solution) was dispensed in separate 96 well plate and diluted with 50% acetonitrile (198 μL) to prepare 100 μM standard solution. Additionally, 100 μM standard solution was tenfold diluted with 50% acetonitrile to prepare 10 μM standard solution. The sample for measuring solubility and two standard solutions were analyzed under the measurement condition determined in pre-investigation to calculate solubilities by area ratios with a standard solution. 
     INDUSTRIAL APPLICABILITY 
     The inventive compound is useful as a preventive and/or therapeutic agent for a disease including type II diabetes, abnormal glucose tolerance, hyperglycemia, insulin resistance, hypo-HDL-emia, hyper-LDL-emia, dyslipidemia, hyperlipidemia, hypertriglyceridemia, hypercholesterolemia, hypertension, arteriosclerosis, angiostenosis, atherosclerosis, obesity, cognitive disorder, glaucoma, retinopathy, dementia, Alzheimer disease, osteoporosis, immune disorder, syndrome X, depression, cardiovascular disease, neurodegenerative disease, etc.