4,7-DIHYDROPYRAZOLO(3,4-B)PYRIDINE DERIVATIVES

Abstract: Novel Ca-blockers, 4,7-dihydropyrazolo[3,4-b]pyridine derivatives having potent antihypertensive and coronary vaso­ dilating actions and useful in treatment for diseases in circula­ tory system, but without systole inhibitory action.

Description: 4,7-DIHYDROPYRAZOLO[3,4-b]PYRIDINE DERIVATIVES BACKGROUND OF THE INVENTION 1) Field of the Invention The compounds this invention provides are novel Cablocker-type cardiovascular agents having potent antihypertensive and coronary vasodilating effects, and useful in treatment for cardiovascular diseases such as angina pectoris, hypertension, cerebrovascular dysfunction, arrhythmia or the like. 2) Prior Art. Compounds having Ca-blocking effect have commonly been used for treatment of cardiovascular diseases such as angina pectoris, hypertention, cerebrovascular dysfunction, arrhythmia or the like, and have become well-known because of their high efficacy. In particular, a series of 1, 4dihydropyridine derivatives have been investigated extensively and developed as Ca-blocker. Examples of useful Ca-blockers are Nifedipine (U.S. Patent Nos. 3,485,847 and 3, 644, 627), Nisoldipine (Japanese Patent Publication No. 56-47185), 2amino-1,4-dihydropyridine derivatives (Jap.Pat.Pub. No. 5720306), Nicardipine (Jap.Unexamined Pat.Pub. No. 49-109384), 2-pyridyl-1,4-dihydropyridine derivatives (Jap. Unexam. Pat. Pub. No. 54-48796), 2-methyldihydropyridine derivatives (Jap. Unexam. Pat.Pub. No. 55-62065) and the like. Some examples of pyrazolodihydropyridine derivatives, the production thereof and their Ca-blocking action are disclosed in Jap.Pat. Application Nos. 57-176763 and 58-166258 by the present inventors. SUMMARY The present invention relates to novel 4,7dihydropyrazolo[3,4-b]pyridine derivatives and production thereof. More particularly it relates to 4,7dihydropyrazollo[3,4-b]pyridine derivatives represented by the formula: EMI2.1 wherein Rl is alkyl of 5 or lore carbons, cycloalkyl which say be snbstituted, cycloalkylalkyl, alkoxyalkyl, cycloalkyloxyalkyl, aryloxyalkyl, alkylthioalkyl, cycloalkylthioalkyl, phenylthioalkyl, (nono-or di-alkylaiino ) alkyl, tetrahydrofurylalkyl, aralkyl which may be substituted by one or two substituents, N-benzylpyrrolidinyl, or N-benzylpiperidinyl; R2 is alkyl; and R3 is cycloalkyl or cycloalkylalkyl; and a process for the production of 4,7dihydropyrazolo[3,4-b]pyridine derivatives represented by the formula: EMI3.1 wherein Rl, R2 and R3 each has the same meaning as defined above, which comprises reactingla compound represented by the formula: EMI3.2 wherein RI has the same meaning as defined above, with a compound represented by the formula: EMI3.3 wherein 22 and R3 each has the sale meaning as defined above. Incidentally, the compounds of this invention have the advantage that they have no systole inhibitory action as an adverse reaction usually seen in the use of the analogous known compounds. The objective conpounds(I) of this invention are prepared through the Michael addition between heterocyclic aries and a, B -unsaturated ketones accompanied by cyclization reaction. DESCRIPTION OF THE PREFERRED ENBODIMENT In the definition in the formula (I) - (m), alkyl of five or more carbons means straight or branched chain C5-C, alkyl, such as n-pentyl, iso-pentyl, sec-pentyl, neo-pentyl, tert-pentyl, n-hexyl, iso-hexyl, sec-hexyl, neo-hexyl, terthexyl, n-heptyl, iso-heptyl, sec-heptyl, neo-heptyl, tertheptyl, n-octyl, iso-octyl, sec-octyl and the like. Cycloalkyl which say be substituted means substituted or unsubstituted C,-C, cycloalkyl, wherein the substituent includes lower alkyls such as methyl, ethyl, n-propyl, isopropyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, n-pentyl, iso-pentyl, neo-pentyl, tert-pentyl and the like; for example, cyclobutyl, cyclopentyl, cyclohexyl, 2-iso-propyl-4-methyl- cyclohexyl and the like are exemplified as the cycloalkyl. Cycloalkylalkyl means Cl-C, alkyl substituted by C3-C, cycloalkyl, wherein C3 -C7 cycloalkyl includes cyclopropyl, cyclobutyl, cyclohexyl, cycloheptyl or the like, and C,-C, alkyl includes methyl, ethyl, propyl, butyl or the like. Alkoxyalkyl means Cl-C, alkyl substituted by Cl-C, alkoxy, wherein Cl-C, alkoxy includes methoxy, ethoxy, npropoxy, iso-propoxy, n-butoxy, iso-butoxy, tert-butoxy or the like, and C,-C, alkyl includes the same examples listed above. Cycloalkyloxyalkyl means Cl-C, alkyl substituted by C,-C, cycloalkyloxy, wherein C,-C, cycloalkyloxy includes cyclobutyloxy, cyclopentyloxy, cyclohexyloxy or the like, and Cl-C, alkyl includes the same as listed above. Aryloxyalkyl means Cl-C, alkyl substituted by aryloxy, particularly phenoxy, wherein C-C, alkyl includes the same as listed above. Alkylthioalkyl means Cl-C, alkyl substituted by C-C, alkylthio, wherein C,-C, alkylthio includes methylthio, ethylthio, n-propylthio, iso-propylthio, n-butylthio, isobutylthio, sec-butylthio, tert-butylthio or the like, and C1- C, alkyl includes the same as listed above. Cycloalkylthioalkyl means Cl-C, alkyl substituted by C,-C, cycloalkylthio, wherein C,-C, cycloalkylthio includes cyclobutylthio, cyclopentylthio, cyclohexylthio, cycloheptylthio or the like, and Cl-C, alkyl includes the same as listed above. Phenylthioalkyl means Cl-C, alkyl substituted by phenylthio, wherein C1-C4 alkyl includes the same as listed above. (Mono- or di-alkylamino)alkyl means C1-C4 alkyl substituted by C1-C4 mono-alkylamino or C2-C8 di-alkylamino, wherein C,-C, mono-alkylamino includes methylamino, ethylamino, n-propylamino, iso-propylamino, n-butylaaino, iso butylanino, sec-butylanino, tert-butylamino and the like; and C2-C8 dialkylamino includes dimethylamino, methylethylamino, methyl(n-propyl)amino, methyl(iso-propyl)amino, diethylamino, aethyl(n-butyl ) amino, aethyl ( iso-butyl )amino, methyl ( sec- butyl)amino, methyl(tert-butyl)amino, ethyl(n-propyl)amino, ethyl(iso-propyl)aiino, ethyl(n-butyl)amino, ethyl(isobutyl)amino, ethyl(sec-butyl)amino, ethyl(tert-butyl)amino, dipropylamino, n-propyl(n-butyl)amino, n-propyl(iso butyl)amino, n-propyl( sec-butyl)anino, n-propyl(tertbutyl)amino, iso-propyl(n-butyl)amino, iso-propyl(isobutyl)amino, iso-propyl(sec-butyl)amino, iso-propyl(tertbutyl)amino, dibutyla ino and the like, and C1-C4 alkyl includes the same as listed above. Tetrahydrofurylalkyl means 2-tetrahydrofuryl(C,-C,)alkyl or 3-tetrahydrofuryl C,-C, alkyl, wherein C-C, alkyl includes the same as listed above. Aralkyl which may be substituted by one or two substituents means substituted or unsubstituted C,-C, aralkyl, wherein the substituents include halogens such as fluoro, chloro, bromo and iodo; and C,-C, alkoxy listed above. More specifically, benzyl, phenetyl, 3phenylpropyl, tolylmethyl, 4-fluorophenethyl, 4-chlorophenethyl, 4-bromophenethyl, 4iodophenethyl, 3,4-dimethoxyphenethyl, 1-methoxy-2-phenethyl and the like are exemplified as the aralkyl. In the definition of R2, alkyl means C-C, alkyl as exemplified above, and in that of R3, cycloalkyl means C,-Cs cycloalkyl, which includes cyclobutyl, cyclopentyl, cyclohexyl and the like. The compound (I) of the present'invention can, as shown in the following scheme, be readily produced by the reaction of &alpha;, ss -unsaturated ketone reagent (E ) with a 5aminopyrazole (m), EMI7.1 wherein R1, R2 and R3 each has the same meaning as identified above. The reaction may be accomplished in the absence or presence of any solvent. Such a solvent as employed for this reaction includes alcohols such as methanol, ethanol, isopropanol, tert-butanol, ethylene glycol and the like; hydrocarbons such as benzene, toluene, xylene and the like; ethers such as ether, tetrahydrofuran, dioxane, glyme, diglyme and the like; halogeno hydrocarbons such as dichloro ethane, chloroforu, dichloroethane, carbon tetrachloride and the like; esters such as ethyl acetate; acetic acid; dimethylformaminde; pyridine; and the like. An acid, an organic base or the like is employed as a catalyst, if necessary. Such an acid includes inorganic acids e.g., sulfuric acid, hydrochloric acid, phosphoric acid and the like; para-toluenesulfonic acid, acetic acid, formic acid and the like as an organic acid; and boron trifluoride, zinc chloride, aluminium chloride, magnesium chloride, tin chloride and the like as a Lewis acid. Such a base includes organic base catalysts e.g., triethylamine, pyridine, pyrrolidine, piperidine and the like. The reaction is completed after a few hours or a few days at room temperaturel - 30-C) or under heating (30 100 C). The starting compounds, 5-aminopyrazole and a, . ss- unsaturated ketone reagents, both of which are employed in the reaction, say be prepared in the manners as shown below, respectively. (i) Preparation of 5-ainopyrazole (M): A 5-aminopyrazole(N) can be produced according to the reaction sequence as shown below. In other words, it can be prepared in a high yield by the cyclization of a hydrazine(N) with a ss -ketonitrile(V ). Processes for the production of the compounds(N) are disclosed in the Jap. Pat. Application Nos. 57-176763 and 58166258 by the present inventors. EMI9.1 wherein R2 and R3 each has the same meaning as defined above, R represents halogen or an ester residue, and M represents an alkali metal. The ss -ketonitriles(V ) are prepared through the reaction of an acid chloride or an ester with an alkali metal salt of acetonitrile. (ii) Preparation of &alpha;, ss -unsaturated ketone reagents(I ): a , ss -Unsaturated ketone reagents( U ) are prepared, as shown in the following scheme, by the condensation reaction of an aldehyde (N) with an acetoacetic ester (IX): the manner of the reaction is desclosed in j. Chem Soc., 81, 1212 (1902): Che7 Ber., 29, 172 (1896): Ann., 218, 170 (1883)! J. Ches Soc., 3092 (1962). EMI10.1 wherein Rl has the sae meaning as defined above. The acetoacetic esters are prepared, in the presence of an acid-(hydrochloric acid, sulfuric acid, phospholic acid and the like) or base-(pyridine, pyrrolidine, piperidine and the like) catalyst, through the reaction of a diketene(X ) with an alcohol(XI). The compounds of the present invention, which are prepared by the reaction of the above-obtained &alpha;, , ss ss- unsaturated ketone reagents( I) with a 5-aminopyrazole(N ), are listed below. (1) 2-Methoxyethyl=3-cyclopentyl-1,6-dimethyl-4-(2nitrophenyl)-4,7-dihydropyrazolo[3,4-b]pyridine-5-carboxylate, (2) 2-Methoxyethyl=3-cyclopentyl-1,6-dimethyl-4-(3 nitrophenyl) -4, 7-dihydropyrazolo[ 3,4-b] pyridine-5-carboxylate, (3) 2-Methoxyethyl=3-cyclohexyl-1,6-dimethyl-4-(2- nitrophenyl)-4,7-dihydropyrazolo[3,4-b]pyridine-5-carboxylate, (4) 2-Methoxyethyl=3-cyclopentylmethyl-1,6-dimethyl-4-(2nitrophenyl)-4,7-dihydropyrazolo[3,4-b]pyridine-5-carboxylate, (5) 2-Isopropoxypropyl=3-cyclopentyl-1,6-dimethyl-4-(2nitrophenyl)-4,7-dihydropyrazolo[3,4-b]pyridine-5-carboxylate, (6) 2-Cyclopentyloxyethyl=3-cyclopentyl-1,6-dimethyl-4-(2 nitrophenyl)-4,7-dihydropyrazolo[3, 4-b] pyridine-5- carboxylate, (7) 2-Cyclohexyloxyethyl=3-cyclopentyl-1,6-dimethyl-4-(2- nitrophenyl)-4,7-dihydropyrazolo[3, 4-b]pyridine-5carboxylate, (8) 2-Tetrahydrofurylmethyl=3-cyclopentyl-1,6-dimethyl-4- (2-nitrophenyl)-4, 7-dihydropyrazolo[3, 4-b]pyridine-5- carboxylate, (9) 2-Phenoxyethyl=3-cyclopentyl-l, 6-dimethyl-4-(2nitrophenyl)-4, 7-dihydropyrazolo[3, 4-b] pyridine-5- carboxylate, (10) 2-Phenoxyethyl=3-cyclopentyl-l, 6-dimethyl-4-(3nitrophenyl)-4, 7-dihydropyrazolo[3, 4-b]pyridine-5- carboxylate, (11) 2-Phenoxyethyl=3-cyclohexyl-l, 6-dimethyl-4-(2nitrophenyl)-4, 7-dihydropyrazolo[3, 4-b]pyridine-5- carboxylate, (12) 2-Methoxyethyl=3-cyclopentyl-1,6-dimethyl-4-(2nitrophenyl)-4,7-dihydropyrazolo[3,4-b]pyridine-5 carboxylate, (13) 2-dimethylaminopropyl=3-cyclopentyl-1,6-dimethyl-4-(2nitrophenyl)-4,7-dihydropyrazolo[3,4-b]pyridine-5carboxylate, (14) N-Benzylpyrrolidin-3-yl=3-cyclopentyl-1,6-dimethyl-4 (2-nitrophenyl)-4,7-dihydropyrazolo[3,4-b]pyridine-5carboxylate, (15) N-Benzylpyrrolidin-4-yl=3-cyclopentyl-1,6-dimethyl-4 (2-nitrophenyl)-4,7-dihydropyrazolo[3,4-b]pyridine-5carboxylate, (16) n-Pentyl=3-cyclopentyl-1,6-dimethyl-4-(2-nitrophenyl)4,7-dihydropyrazolo[3,4-b]pyridine-5-carboxylate, (17) Phenethyl=3-cyclopentyl-1,6-dixethyl-4-(2-nitrophenyl)- 4,7-dihydropyrazolo[3,4-b]pyridine-5-carboxylate, (18) 4-Chlorphenethyl=3-cyclopentyl-1,6-dimethyl-4-(2nitrophenyl)-4,7-dihydropyrazolo[3,4-b]pyridine-5carboxylate, (19) 3,4-Dimethoxyphenethyl=3-cyclopentyl-1,6-dimethyl-4-(2nitrophenyl)-4, 7-dihydropyrazolo[3, 4-b]pyridine-5- carboxylate, (20) 1-Methoxy-2-phenylethyl=3-cyclopentyl-1,6-dimethyl-4 (3-nitrophenyl)-4,7-dihydropyrazolo[3,4-b]pyridine-5carboxylate, (21) 2-Isopropyl-4-methylcyclohexyl=3-cyclopentyl-1, 6dimethyl-4-(3-nitrophenyl)-4, 7-dihydropyrazolo[3, 4-b]- pyridine-5-carboxylate, (22) 2-Phenylthioethyl=3-cyclopentyl-1, 6-dimethyl-4-(2nitrophenyl)-4, 7-dihydropyrazolo[3, 4-b]pyridine-5- carboxylate, (23) 2-Isopropylthioethyl=3-cyclopentyl-1,6-dimethyl-4-(2nitrophenyl)-4,7-dihydropyrazolo[3,4-b]pyridine-5carboxylate, (24) 2-Cyclopetnylthioethyl=3-cyclopentyl-1,6-dimethyl-4 (2-nitrophenyl)-4, 7-dihydropyrazolo[3, 4-b]pyridine-5- carboxylate, (25) 2-Cyclopentylethyl=3-cyclopentyl-1, 6-dimethyl-4-(2nitrophenyl)-4, 7-dihydropyrazolo[3, 4-b]pyridine-5- carboxylate, (25) Cyclohexylmethyl=3-cyclopentyl-1,6-dimethyl-4-(2nitrophenyl)-4, 7-dihydropyrazolo[ 3, 4-b]pyridine-5- carboxylate, (27) Cyclopentyl=3-cyclopentyl-1, 6-dimethyl-4-(2 nitrophenyl) -4, 7-dihydropyrazolo[3, 4-b]pyridine-5- carboxylate, (28) Cyclohexyl=3-cyclopentyl-1, 6-dimethyl-4-(2nitrophenyl)-4, 7-dihydropyrazolo[3, 4-b]pyridine-5- carboxylate. In addition, the acid addition salts, which can be obtained froa the above-listed compounds, can be used as an active ingredient in this invention. Some examples of the acids capable to form such salts are inorganic acids such as hydrohalogenic acid (hydrochloric acid, hydrobromic acid or the like), sulfuric acid, nitric acid, phospholic acid or the like: and organic acids such as acetic acid, propionic acid, oxalic acid, salonic acid, succinic acid, glutaric acid, adipic acid, salic acid, saleic acid, fumaric acid, citric acid, benzoic acid, siethanesulfonic acid or the like. (Effect and Use) The novel compounds of the present invention have the advantage that they have excellent antihypertensive and coronary vasodilating actions derived from Ca-blocking action, but have no systole inhibitory action which is one of adverse reactions and have been a defect of the conventional Cablockers. The biological tests of the following compounds were perforeed as explained below. (Compounds Tested) (A): Nifedipine (B): 2-Methoxyethyl=3-cyclopentyl-1,6-dimethyl-4-(2- nitrophenyl)-4,7-dihydropyrazolo[3,4-b]pyridine-5-carboxylate (C): 2-Methoxyethyl=3-cyclopentyl-1,6-dimethyl-4-(3- nitrophenyl)-4,7-dihydropyrazolo[3,4-b]pyridine-5-carboxylate (D) 2-Methoxyethyl=3-cyclopentyl-1,6-dimethyl-4-(2nitrophenyl)-4,7-dihydropyrazolo[3,4-b]pyridine-5-carboxylate (E): 2-Methoxyethyl=3-cyclopentylmethyl-1,6-dimethyl-4-(2nitrophenyl)-4,7-dihydropyrazolo[3,4-b]pyridine-5-carboxylate (F): 3-Isopropoxypropyl=3-cyclopentyl-1,6-dimethyl-4-(2nitrophenyl)-4,7-dihydropyrazolo[3,4-b]pyridine-5-carboxylate (G): 2-Cyclopentyloxyethyl=3-cyclopentyl-1,6-dimethyl-4-(2- nitrophenyl)-4,7-dihydropyrazolo[3,4-b]pyridine-5-carboxylate (H): 2-Tetrahydrofurylmethyl=3-cyclopentyl-1,6-dimethyl-4 (2-nitrophenyl)-4,7-dihydropyrazolo[3,4-b]pyridine-5carboxylate (I): 2-Phenoxyethyl=3-cyclopentyl-1,6-dimethyl-4-(2- nitrophenyl)-4,7-dihydropyrazolo[3,4-b]pyridine-5-carboxylate (J): 2-Methylthioethyl=3-cyclopentyl-1,6-dimethyl-4-(2nitrophenyl)-4,7-dihydropyrazolo[3,4-b]pyridine-5-carboxylate (K): Phenethyl=3-cyclopentyl-1,6-dimethyl-4-(2-nitrophenyl)4,7-dihydropyrazolo[3,4-b]pyridine-5-carboxylate (L): 4-Chlorophenethyl=3-cyclopentyl-1,6-dimethyl-4-(3- nitrophenyl)-4,7-dihydropyrazolo[3,4-b]pyridine-5-carboxylate (M) 3,4-Dimethoxyphenethyl=3-cyclopentyl-1,6-dimethyl-4-(3nitrophenyl)-4,7-dihydropyrazolo[3,4-b]pyridine-5-carboxylate (Test Method) (1) Antihypertensive Action: Female Spontaneously Hypertensive Rats(hereinafter referred to as SHR) with 160 mmHg of systolic pressure were employed without anaesthetization. The systolic pressure was, after SHRs were kept warm at 50 C for 2 - 3 minutes, bloodlessly measured by the tail-cuff method (Japan J. Pharmacol, 28, 617 (1978)] using a Physiograph and an Electrosphygiosanometer (DMP-4B, PE-300, Narco Biosystens, Inc., Houston). Each compound was interaperitoneally administered to SHR at a dose of 3 Mg per kilograms. (2) Coronary Vasodilating Action and Systole Inhibitory Action: Guinea pigs with 400 - 800g of body weight were strongly hit on their heads and the cartoid artery of each Guinea pigs was cut down in order to sake them bloodless. The heart was isolated and perfused with at a constant pressure (50 cm H2O) by the Langendorff method [Basic Pharmacology & BR< Therapeutics, 9(4), 181 (1981) ]. Krebs-Ringer bicarbonate solution (27 ) containing 0.5Z defibrinated blood was employed as a perfusate, into which a mixed gas of 95X oxygen and 5% carbon dioxide was continuously introduced. The flowing perfusate was led into a drop counter, and the changes of the flow & i.e. increase and decrease are regarded as the respective indications for coronary vasodilation and vasoconstriction. The isomeric contraction of apex and the number of drops of the coronary perfusate were recorded on a Recticorder (RJG 3006, Nihon Koden) by way of an F-D Pick-up (SB-1T, Nihon Koden). Each of the test compounds at a dose of 0.1 g g was administered through the short rubber tube connecting the aorta and the cannula. (Results) Antihypertensive action is shown in a maximal decrease of blood pressure, i.e., a maximum difference between systolic pressures after and before the administration of the test compound; along with which the duration period is also shown. Coronary vasodilating action is shown in changes of the quantiy of the perfusate, and systole inhibitory action is shown in those of inotropic tension. Table 1 Antihypertensive action, coronary vasodilating action and systole inhibitory action: EMI17.1 <tb> <SEP> Maximum <SEP> Duration <SEP> of <SEP> Perfusion <SEP> Change <SEP> of <SEP> Contrac <tb> Compounds <SEP> Hypertension <SEP> Effect <SEP> Flow <SEP> Change <SEP> tile <SEP> Tention <tb> <SEP> (mmHg) <SEP> (hours) <SEP> (%) <SEP> (%) <SEP> <tb> <SEP> (A) <SEP> 45 <SEP> 6 <SEP> +38 <SEP> -15 <tb> <SEP> (B) <SEP> 45 <SEP> 6 <SEP> +28 <SEP> 0 <tb> <SEP> (C) <SEP> 36 <SEP> 6 <SEP> +15 <SEP> 0 <tb> <SEP> (D) <SEP> 65 <SEP> 6 <SEP> +32 <SEP> 0 <tb> <SEP> (E) <SEP> 26 <SEP> 6 <SEP> +20 <SEP> 0 <tb> <SEP> (F) <SEP> 53 <SEP> 6 <SEP> +65 <SEP> 0 <tb> <SEP> (G) <SEP> 53 <SEP> 6 <SEP> +67 <SEP> 0 <tb> <SEP> -(H) <SEP> 0 <SEP> - <SEP> <SEP> µ34 <SEP> 0 <tb> <SEP> (I) <SEP> 74 <SEP> 6 <SEP> +43 <SEP> 0 <tb> <SEP> (J) <SEP> 20 <SEP> 6 <SEP> +68 <SEP> 0 <tb> <SEP> (K) <SEP> 75 <SEP> 6 <SEP> +63 <SEP> 0 <tb> <SEP> (L) <SEP> 74 <SEP> 6 <tb> <SEP> (H) <SEP> 86 <SEP> 6 <tb> Since the compounds of this invention, as clearly seen from the above-listed results, show the highly antihypertensive and coronary vasodilating actions but no systole inhibitory action, they can be used as a cardiovascular agent with lesser adverse reactions to human or anjials. The compounds of this invention and the acid addition salts thereof can orally or pareterally be administered to human or animals and can be manufactured in various foriulations in compliance with the usage. They, for instance, can be in a forailation of-tablets, capsules, pills, granules, fine granules, aqueous solutions, emulsions or the like. In the course of the formulation, conventional carriers or diluents such as lactose, sucrose, starch, cellulose, talc, magnesium stearate, magnesium oxide, calcium sulfate, powdered gac arabic, gelatin, sodium arginate, sodium benzoate, stearic acid and the like are employed. Injections used may be in a formulation of a solution with distilled water, saline solution, Ringer solution or the like, or 9 suspension in sesame oil. The compounds of this invention may be administered to an adult orally at a dose of about 1 - 50 mg a day, or intravenously at about 0.5 - 20 ig a day. The present invention is further described in the following Examples and Preparations. EXAMPLE 1 Preparation of 2-methoxyethyl=3-cyclopentyl-1 ,6-dimethyl-4-(2- nitrophenyl)-4,7-dihydropyrazolol3,4-b]pyridine-5-carboxylate 3. EMI19.1 In 6 ml of tert-butÅanol are dissolved 0.90 g (3.05 mMol.) of 2-methoxyethyl=2-nitrobenzylideneacetoacetate 1 and 0.50 g (3.05 mMol.) of 3-cyclopentyl-5-amino-1-methylpyrazole 2, and the solution is allowed to react at 80O for 3 hours, then evaporated under reduced pressure. The resulting residue is crystallized from ether, filtered and washed with a small amount of ether to give the 1.15 g of the titled compound 3. This is recrystallized from ethanol to give 0.92 g of yellow prises in 59.6X yield, mp. 196-1980C. Elementary Analysis: Calcd. (%) for C23H25N4O5: C, 62.71; H, 6.41; N, 12.72. Found (X): C, 62.69; H, 6.20; N, 12.82. IR(Nujol) # max: 3260(NH), 1690(C=O), 1360(NIO2) cm-1. NMR(CDCl3) 8 pp : 0.97-2.03 (8H, m), 2.33, 3.27, 3.63 (3H x 3, s), 2.92 (1H, m), 3.51 (28, m), 4.13 (2H, m), 5.92 (1H, s), 6.677 (1H, br, s), 7.00-7.73 (4H, m). EXAMPLES 2 - 33 EMI20.1 wherein R', Rê and RS each has the same meaning as defined above. A solution of compounds (I ) and (II) in a solvent is allowed to react in nitrogen atmosphere at room temperature or under heating and then evaporated. The residue is crystallized from ether, or chromatographed on silica gel to give the objective compound (I). This, if needed, is purified by recrystallization. The objective compounds of the present invention can, which are listed in the following Table 2, be prepared in the manner commonly described above. Details of the reaction conditions are summarized in Table 3. Additionally, recrystallization solvents, appearance (crystal form, color), molecular formula and the result by elemental analysis in each compound or the acid addition salt are summarized in Table 4; and the IR- and NMR-spectrum data are shown in Table 5. EMI22.1 Table 2 (No. 1) EMI22.2 <tb> rarpl <SEP> RI <SEP> R2 <SEP> R3 <SEP> Position <SEP> Yield <tb> <SEP> No. <SEP> of <SEP> -NOa <SEP> (%) <tb> <SEP> 3 <SEP> -CE2CE20CE3 <SEP> 1 <SEP> 1 <SEP> 2 <SEP> 72.1 <tb> <SEP> 4 <SEP> 1. <SEP> -CH2-a <SEP> 51.5 <tb> <SEP> 5 <SEP> 2CE2C820C <SEP> % <SEP> 3 <SEP> w <SEP> < <SEP> 75.4 <tb> <SEP> 6a) <SEP> H2CK2O <SEP> '1 <SEP> 1 <SEP> 1 <SEP> 77-0 <tb> <SEP> 7a) <SEP> -CK2CE20 <SEP> 4 <SEP> 78.9 <tb> 8 <SEP> ¯CE2 <SEP> I <SEP> * <SEP> 1 <SEP> 81-5 <tb> <SEP> gb) <SEP> CE2CH20 <SEP> 4 <SEP> w <SEP> . <SEP> 81.9 <tb> <SEP> lOa) <SEP> w <SEP> I <SEP> - <SEP> 3 <SEP> 89.7 <tb> <SEP> l7a) <SEP> I <SEP> w <SEP> < <SEP> 2 <SEP> 81.7 <tb> <SEP> 12b) <SEP> 2 <SEP> 2 <SEP> 3 <SEP> 31.5 <tb> <SEP> cH <SEP> 42.3 <tb> <SEP> 13b) <SEP> -CE2C <SEP> 2 <SEP> 2 <SEP> < <SEP> 3 <SEP> w <tb> <SEP> 3 <tb> 14 <SEP> < <SEP> -C2 <SEP> 1 <SEP> 1 <SEP> w <SEP> 60.7 <tb> <SEP> 15b) <SEP> CkCR-" <SEP> I <SEP> 4 <SEP> 54.7 <tb> <SEP> 16a) <SEP> -(CE2)i-CE3 <SEP> w <SEP> w <SEP> 1 <SEP> 72-8 <tb> <SEP> 17 <SEP> 2 <SEP> 2 <SEP> 4 <SEP> -CHaCR2-11 <SEP> 67.2 <tb> Table 2 (No.2) EMI23.1 <tb> Example <SEP> R1 <SEP> R2 <SEP> R3 <SEP> Position <SEP> Yield <tb> <SEP> No. <SEP> . <SEP> of <SEP> -N02 <SEP> (%) <tb> <SEP> ôt) <SEP> -CH2cH2 <SEP> Cl <SEP> -cH <SEP> 2 <SEP> 76. <SEP> O <tb> <SEP> ) <SEP> -c2cH2R3 <SEP> ml <SEP> u <SEP> 74.8 <tb> <SEP> 1 <SEP> 3 <tb> <SEP> OCR <tb> <SEP> 20 <SEP> CRCR32 <SEP> 'S <SEP> U <SEP> 3 <SEP> 96.2 <tb> <SEP> 21a) <SEP> oH3 <SEP> n <SEP> n <SEP> n <SEP> 75 <SEP> 6 <SEP> 9 <tb> <SEP> cE3 <tb> <SEP> 22a) <SEP> cR2cR2s <SEP> U <SEP> 2 <SEP> 2 <SEP> 71.4 <tb> <SEP> 23d) <SEP> -CH2CH2S-Cf3 <SEP> I <SEP> w <SEP> n <SEP> 77.5 <tb> <SEP> 3 <tb> <SEP> 24) <SEP> CH2CH2S"a <SEP> n <SEP> n <SEP> n <SEP> 77.8 <tb> <SEP> 23a) <SEP> -ci2ar2 <SEP> U <SEP> U <SEP> 72.8 <tb> <SEP> 26a) <SEP> CH20 <SEP> n <SEP> n <SEP> n <SEP> 76.8 <tb> <SEP> 27'so <SEP> U <SEP> {I <SEP> n <SEP> n <SEP> 67.0 <tb> <SEP> 28t) <SEP> ¯0 <SEP> 64.3 <tb> a): Hydrochloride b): Oxalate Table 2 (No. 3) EMI24.1 Example <SEP> R1 <SEP> Rê <SEP> R <SEP> Position <SEP> Yield <tb> No. <SEP> of <SEP> -NO2 <SEP> (%) <tb> 29a) <SEP> ###-Cl <SEP> " <SEP> " <SEP> 3 <SEP> 73.2 <tb> 30a) <SEP> ###-OMe <SEP> " <SEP> " <SEP> " <SEP> 56.6 <tb> <SEP> OMe <tb> 31a) <SEP> ###-Cl <SEP> " <SEP> " <SEP> " <SEP> 58.2 <tb> <SEP> Cl <tb> 32a) <SEP> ###-Br <SEP> " <SEP> " <SEP> " <SEP> 70.8 <tb> 33a) <SEP> ### <SEP> " <SEP> " <SEP> " <SEP> 67.8 <tb> <SEP> CF3 <tb> EMI25.1 Table 3 (No. 1) EMI25.2 <tb> <SEP> Amount <SEP> used <SEP> g <SEP> (mmol) <SEP> Solvent <SEP> Reaction <SEP> Reaction <tb> Example <SEP> Temp. <SEP> Time <tb> <SEP> No. <SEP> (ml) <SEP> ( C) <SEP> (hrs.) <tb> <SEP> Compd. <SEP> (II) <SEP> Compd.(III) <tb> <SEP> 2 <SEP> 0.88(3.01) <SEP> 0.50(3.05) <SEP> t-butanol <SEP> (5) <SEP> 80 <SEP> 3 <tb> <SEP> 3 <SEP> 0.88(3.01) <SEP> 0.54(3.01) <SEP> " <SEP> (6) <SEP> 80 <SEP> 3 <tb> <SEP> 4 <SEP> 0.88(3.01) <SEP> 0.54(3.01) <SEP> i-isopropanol <SEP> (2) <SEP> 70 <SEP> 72 <tb> <SEP> 5 <SEP> 0.67(2.0) <SEP> 0.33(2.0) <SEP> " <SEP> (2) <SEP> 80 <SEP> 15 <tb> <SEP> 6 <SEP> 0.57(1.64) <SEP> 0.27(1.64) <SEP> " <SEP> (2) <SEP> 80 <SEP> 24 <tb> <SEP> 7 <SEP> 1.04(2.87) <SEP> 0.47(2.87) <SEP> " <SEP> (10) <SEP> 80 <SEP> 20 <tb> <SEP> 8 <SEP> 0.64(2.0) <SEP> 0.33(2.0) <SEP> " <SEP> (2) <SEP> 80 <SEP> 24 <tb> <SEP> 9 <SEP> 0.71(2.0) <SEP> 0.33(2.0) <SEP> " <SEP> (2) <SEP> 80 <SEP> 24 <tb> <SEP> 10 <SEP> 1.00(2.81) <SEP> 0.47(2.87) <SEP> " <SEP> (10) <SEP> 80 <SEP> 3 <tb> <SEP> 11 <SEP> 0.90(2.53) <SEP> 0.45(2.53) <SEP> " <SEP> (9) <SEP> 80 <SEP> 20 <tb> <SEP> 12 <SEP> 0.62(2.0) <SEP> 0.33(2.0) <SEP> " <SEP> (2) <SEP> 80 <SEP> 24 <tb> <SEP> 13 <SEP> 0.64(2.0) <SEP> 0.33(2.0) <SEP> " <SEP> (4) <SEP> 80 <SEP> 18 <tb> <SEP> 14 <SEP> 2.01(5.08) <SEP> 0.84(5.09) <SEP> " <SEP> (5) <SEP> 80 <SEP> 17 <tb> <SEP> 15 <SEP> 1.01(2.46) <SEP> 0.41(2.48) <SEP> " <SEP> (15) <SEP> 80 <SEP> 19 <tb> <SEP> 16 <SEP> 0.89(2.92) <SEP> 0.48(2.92) <SEP> " <SEP> (9) <SEP> 80 <SEP> 19 <tb> <SEP> 17 <SEP> 0.68(2.0) <SEP> 0.33(2.0) <SEP> " <SEP> (2) <SEP> 80 <SEP> 16 <tb> <SEP> 18 <SEP> 0.95(2.54 <SEP> 0.42(2.54) <SEP> " <SEP> (10) <SEP> 80 <SEP> 20 <tb> Table 3 (No.2) EMI26.1 <tb> <SEP> Amount <SEP> g <SEP> (mmol) <SEP> Solvent <SEP> Reaction <SEP> Reaction <tb> Example <SEP> Used <SEP> Temp. <SEP> Time <tb> <SEP> No. <SEP> (ml) <SEP> ( C) <SEP> (hrs.) <tb> <SEP> Compd. <SEP> (II) <SEP> Compd.(III) <tb> <SEP> 19 <SEP> 1.13(2.82) <SEP> 0.47(2.82) <SEP> i-propanol <SEP> (10) <SEP> 80 <SEP> 20 <tb> <SEP> 20 <SEP> 3.39(9.19) <SEP> 1.52(9.19) <SEP> t-butanol <SEP> (10) <SEP> 80 <SEP> 2 <tb> <SEP> 21 <SEP> 4.09(10.9) <SEP> 1.81(10.9) <SEP> " <SEP> (15) <SEP> 80 <SEP> 3 <tb> <SEP> 22 <SEP> 1.0 <SEP> (2.7) <SEP> 0.45(2.7) <SEP> " <SEP> (5) <SEP> 80 <SEP> 16 <tb> <SEP> 23 <SEP> 0.92(2.72) <SEP> 0.45(2.7) <SEP> i-propanol <SEP> (5) <SEP> 80 <SEP> 20 <tb> <SEP> 24 <SEP> 1.08(2.96) <SEP> 0.49(2.96) <SEP> " <SEP> (5) <SEP> 80 <SEP> 20 <tb> <SEP> 25 <SEP> 1.05(3.15) <SEP> 0.52(3.15) <SEP> " <SEP> (5) <SEP> 80 <SEP> 20 <tb> <SEP> 26 <SEP> 1.33(4.0) <SEP> 0.66(4.0) <SEP> t-butanol <SEP> (10) <SEP> 80 <SEP> 20 <tb> <SEP> 27 <SEP> 1.02(3.34) <SEP> 0.55(3.34) <SEP> i-propanol <SEP> (5) <SEP> 80 <SEP> 20 <tb> <SEP> 28 <SEP> 1.01(3.19) <SEP> 0.53(3.19) <SEP> " <SEP> (5) <SEP> 80 <SEP> 19 <tb> Table 3 (No. 3) EMI27.1 Example <SEP> Amount <SEP> used <SEP> g <SEP> (mmol) <SEP> Solvent <SEP> Reaction <SEP> Reaction <tb> <SEP> Temp. <SEP> Time <tb> No. <SEP> Compd. <SEP> (II) <SEP> Compd.(III) <SEP> (ml) <SEP> ( C) <SEP> (hrs.) <tb> 29 <SEP> 1.07(2.86) <SEP> 0.47(2.86) <SEP> " <SEP> (8) <SEP> 80 <SEP> 2.5 <tb> 30 <SEP> 1.00(2.51) <SEP> 0.42(2.51) <SEP> " <SEP> (6) <SEP> 80 <SEP> 3 <tb> 31 <SEP> 2.00(4.9) <SEP> 0.81(4.9) <SEP> " <SEP> (10) <SEP> 80 <SEP> 24 <tb> 32 <SEP> 1.67(4.0) <SEP> 0.66(4.0) <SEP> " <SEP> (10) <SEP> 70 <SEP> 48 <tb> 33 <SEP> 1.22(3.0) <SEP> 0.50(3.0) <SEP> " <SEP> (10) <SEP> 70 <SEP> 48 <tb> EMI28.1 Table 4 (No. 1) EMI28.2 <SEP> Elementary <SEP> Analysis <SEP> (%) <tb> <SEP> o) <SEP> Solvent <SEP> Molecular <tb> Example <SEP> Appear- <SEP> for <SEP> m.p. <SEP> ( C) <SEP> Formula <SEP> Calcd. <SEP> Found <tb> No. <SEP> ance <SEP> Recrystallizat <SEP> ion <SEP> C <SEP> H <SEP> N <SEP> O <SEP> H <SEP> N <tb> 2a) <SEP> YP <SEP> ethanol <SEP> 167 <SEP> - <SEP> 173 <SEP> C23H29ClN4O5 <SEP> 57.92 <SEP> 6.13 <SEP> 11.75 <SEP> 57.84 <SEP> 6.18 <SEP> 11.65 <tb> 3 <SEP> YP <SEP> ethanol <SEP> 200 <SEP> - <SEP> 202 <SEP> C24H30N4O5 <SEP> 63.42 <SEP> 6.65 <SEP> 12.33 <SEP> 63.26 <SEP> 6.41 <SEP> 12.36 <tb> 4 <SEP> YP <SEP> i-propyl <SEP> ether <SEP> 148 <SEP> - <SEP> 149 <SEP> C24H30N4O5 <SEP> 63.42 <SEP> 6.65 <SEP> 12.33 <SEP> 63.37 <SEP> 6.57 <SEP> 12.39 <tb> 5 <SEP> YP <SEP> i-propyl <SEP> ether <SEP> 101 <SEP> - <SEP> 103 <SEP> C26H30N4O5 <SEP> 64.71 <SEP> 7.10 <SEP> 11.61 <SEP> 64.89 <SEP> 7.07 <SEP> 11.53 <tb> 6a) <SEP> YP <SEP> acetone <SEP> 119 <SEP> - <SEP> 121a) <SEP> C27H35ClN4O5#H2O <SEP> 59.06 <SEP> 6.79 <SEP> 10.20 <SEP> 59.15 <SEP> 6.55 <SEP> 10.08 <tb> 7a) <SEP> YP <SEP> acetone/ether <SEP> 115 <SEP> - <SEP> 118a) <SEP> C28H37ClN4O5 <SEP> 61.70 <SEP> 6.84 <SEP> 10.28 <SEP> 61.61 <SEP> 6.85 <SEP> 10.01 <tb> 8 <SEP> YP <SEP> i-propanol <SEP> 153 <SEP> - <SEP> 154 <SEP> C25H30N4O5 <SEP> 64.36 <SEP> 6.48 <SEP> 12.01 <SEP> 64.25 <SEP> 6.47 <SEP> 11.90 <tb> 9b) <SEP> YP <SEP> methylene <SEP> 171 <SEP> - <SEP> 173b) <SEP> C30H32N4O9#H2O <SEP> 59.01 <SEP> 5.61 <SEP> 9.18 <SEP> 58.59 <SEP> 5.20 <SEP> 8.74 <tb> 10a) <SEP> P <SEP> acetone <SEP> 145 <SEP> - <SEP> 150a) <SEP> C28H31ClN4O5 <SEP> 62.39 <SEP> 5.80 <SEP> 10.39 <SEP> 62.17 <SEP> 5.81 <SEP> 10.33 <tb> 11a) <SEP> YP <SEP> acetone <SEP> 125 <SEP> - <SEP> 130a) <SEP> C29H35ClN4O5#H2O <SEP> 61.00 <SEP> 6.18 <SEP> 9.81 <SEP> 60.59 <SEP> 5.99 <SEP> 9.66 <tb> 12 <SEP> YP <SEP> i-propyl <SEP> ether <SEP> 124 <SEP> - <SEP> 126b) <SEP> C25H30N4O85#1/2H2O <SEP> 54.04 <SEP> 5.62 <SEP> 10.08 <SEP> 54.28 <SEP> 5.36 <SEP> 10.05 <tb> 13b) <SEP> YP <SEP> acetone <SEP> 134 <SEP> - <SEP> 136b) <SEP> C27H35N5#2H2O <SEP> 54.63 <SEP> 6.62 <SEP> 11.80 <SEP> 54.73 <SEP> 6.21 <SEP> 11.87 <tb> Table 4 (No. 2) continued from No. 1 EMI29.1 <SEP> Elementary <SEP> Analysis <SEP> (%) <tb> <SEP> o) <SEP> Solvent <SEP> Molecular <tb> Example <SEP> Appear- <SEP> for <SEP> m.p. <SEP> ( C) <SEP> Formula <SEP> Calcd. <SEP> Found <tb> No. <SEP> ance <SEP> Recrystallizat <SEP> ion <SEP> C <SEP> H <SEP> N <SEP> O <SEP> H <SEP> N <tb> 14 <SEP> YA <SEP> - <SEP> - <SEP> C33H37N5O8 <tb> 15b) <SEP> YP <SEP> methanol <SEP> 180 <SEP> - <SEP> 182b) <SEP> C34H39N5O8#1/2H2O <SEP> 62.37 <SEP> 6.16 <SEP> 10.70 <SEP> 62.23 <SEP> 6.15 <SEP> 10.71 <tb> 16a) <SEP> YP <SEP> ethyl <SEP> acetate <SEP> 110 <SEP> - <SEP> 113a) <SEP> C24H33ClN4O4 <SEP> 60.44 <SEP> 6.97 <SEP> 11.75 <SEP> 60.01 <SEP> 6.97 <SEP> 11.45 <tb> 17b) <SEP> YN <SEP> acetone <SEP> 180 <SEP> - <SEP> 182b) <SEP> C30H32N4O8#H2O <SEP> 60.60 <SEP> 5.76 <SEP> 9.42 <SEP> 60.60 <SEP> 5.44 <SEP> 9.33 <tb> 18a) <SEP> YP <SEP> acetone <SEP> 166 <SEP> - <SEP> 170a) <SEP> C28H30Cl2N4O4 <SEP> 60.33 <SEP> 5.42 <SEP> 10.05 <SEP> 60.10 <SEP> 5.52 <SEP> 9.85 <tb> 19a) <SEP> YP <SEP> acetone <SEP> 128 <SEP> - <SEP> 130a) <SEP> C30H35ClN4O6#1/2H2O <SEP> 60.86 <SEP> 6.13 <SEP> 9.46 <SEP> 61.02 <SEP> 6.20 <SEP> 9.12 <tb> 20 <SEP> YA <SEP> - <SEP> - <SEP> C29H32N4O5 <SEP> 67.42 <SEP> 6.24 <SEP> 10.85 <tb> 21 <SEP> P1 <SEP> acetone <SEP> 164 <SEP> - <SEP> 170a) <SEP> C30H41Cl2N4O4 <SEP> 64.68 <SEP> 7.42 <SEP> 10.06 <SEP> 64.61 <SEP> 7.41 <SEP> 9.98 <tb> 22a) <SEP> YN <SEP> acetone <SEP> 125 <SEP> - <SEP> 127a) <SEP> C28H31Cl2N4O4 <SEP> 60.58 <SEP> 5.63 <SEP> 10.09 <SEP> 60.60 <SEP> 5.91 <SEP> 9.63 <tb> 23a) <SEP> YP <SEP> acetone <SEP> 152 <SEP> - <SEP> 155a) <SEP> C25H33Cl2N4O4S <SEP> 57.63 <SEP> 6.38 <SEP> 10.75 <SEP> 57.43 <SEP> 6.43 <SEP> 10.63 <tb> 24a) <SEP> YP <SEP> acetone <SEP> 148 <SEP> - <SEP> 150a) <SEP> C27H35Cl2N4O4S <SEP> 59.28 <SEP> 6.45 <SEP> 10.24 <SEP> 59.30 <SEP> 6.66 <SEP> 10.21 <tb> 25a) <SEP> YP <SEP> acetone <SEP> 145 <SEP> - <SEP> 150a) <SEP> C27H35Cl2N4O4 <SEP> 62.97 <SEP> 6.85 <SEP> 10.88 <SEP> 62.64 <SEP> 6.97 <SEP> 10.80 <tb> 26a) <SEP> YP <SEP> ethanol <SEP> 179 <SEP> - <SEP> 184a) <SEP> C27H35Cl2N4O4 <SEP> 62.96 <SEP> 6.85 <SEP> 10.88 <SEP> 62.78 <SEP> 9.81 <SEP> 10.73 <tb> 27a) <SEP> YP <SEP> acetone <SEP> 141 <SEP> - <SEP> 150a) <SEP> C25H31Cl2N4O4 <SEP> 61.66 <SEP> 6.42 <SEP> 11.50 <SEP> 61.21 <SEP> 6.31 <SEP> 11.30 <tb> 28a) <SEP> YP <SEP> acetone <SEP> 150 <SEP> - <SEP> 155a) <SEP> C26H33Cl2N4O4 <SEP> 62.33 <SEP> 6.64 <SEP> 11.18 <SEP> 62.10 <SEP> 6.46 <SEP> 11.25 <tb> a) : Hydrochloride, b): Oxalate c) YP = Yellow ; YN = Yellow ; YA = Yellow ; P = Colorless ; P1 = Colorless prism Needless Amorphous Prisma Plates Table 4 (No. 3) EMI30.1 <SEP> Elementary <SEP> Analysis <SEP> (%) <tb> <SEP> o) <SEP> Solvent <SEP> Molecular <tb> Example <SEP> Appear- <SEP> for <SEP> m.p. <SEP> ( C) <SEP> Formula <SEP> Calcd. <SEP> Found <tb> No. <SEP> ance <SEP> Recrystallizat <SEP> ion <SEP> C <SEP> H <SEP> N <SEP> O <SEP> H <SEP> N <tb> 29a) <SEP> YP <SEP> " <SEP> 137 <SEP> - <SEP> 140a <SEP> C28H30ClN4O4 <SEP> 60.32 <SEP> 5.42 <SEP> 10.05 <SEP> 60.20 <SEP> 5.65 <SEP> 9.68 <tb> 30a) <SEP> YP <SEP> ethanol <SEP> 150 <SEP> - <SEP> 152a <SEP> C30H35ClN4O6 <SEP> 61.80 <SEP> 6.05 <SEP> 9.61 <SEP> 61.77 <SEP> 5.95 <SEP> 9.54 <tb> 31a) <SEP> YN <SEP> " <SEP> 124 <SEP> - <SEP> 126a <SEP> C28H29ClN4O4 <SEP> 1/3H2O <SEP> 56.23 <SEP> 5.02 <SEP> 9.36 <SEP> 56.66 <SEP> 5.42 <SEP> 8.90 <tb> 32a) <SEP> YP <SEP> " <SEP> 197 <SEP> - <SEP> 200a <SEP> C28H30BrClN4O4 <SEP> 55.82 <SEP> 4.98 <SEP> 9.30 <SEP> 55.62 <SEP> 4.90 <SEP> 9.30 <tb> 33a) <SEP> CP <SEP> " <SEP> 147 <SEP> - <SEP> 149a <SEP> C29H30ClF3N4O4 <SEP> 58.88 <SEP> 5.07 <SEP> 9.47 <SEP> 58.78 <SEP> 4.96 <SEP> 9.40 <tb> a) : Hydrochloride, b): Oxalate c) YP = Yellow ; YN = Yellow ; YA = Yellow ; P = Colorless ; P1 = Colorless prism Needless Amorphous Prisma Plates Table 5 (No. 1) EMI31.1 <SEP> IR <SEP> (#maxcm-1) <SEP> NMR <SEP> (#ppmCDCl3)* <tb> Example <tb> No. <SEP> NH <SEP> CO <SEP> NO2 <tb> 2 <SEP> 3440 <SEP> 1690 <SEP> 1350 <SEP> 1.25-1.92(8H,m), <SEP> 2.38, <SEP> 3.32, <SEP> 3.63(3H <SEP> x <SEP> 3,s), <SEP> 2.58(1H,m), <SEP> 3.51(2H,m), <SEP> 4.14(2H,m), <tb> <SEP> 5.25(1H,s), <SEP> 7.13-8.08(5H,m) <tb> 3 <SEP> 3270 <SEP> 1695 <SEP> 1360 <SEP> 0.77-2.32(10H,m), <SEP> 2.35, <SEP> 3.28, <SEP> 3.65(3H <SEP> x <SEP> 3, <SEP> s), <SEP> 2.50(1H,m), <SEP> 3.50(2H,m), <SEP> 4.13(2H,m), <tb> <SEP> 5.95(1H,s), <SEP> 7.00(1H,br,s), <SEP> 7.13-7.80(4H,m) <tb> 4 <SEP> 3270 <SEP> 1698 <SEP> 1378 <SEP> 0.83-1.77(9H,m), <SEP> 2.72-2.48(2H,m), <SEP> 2.38, <SEP> 3.30, <SEP> 3.67(3H <SEP> x <SEP> 3,s), <SEP> 3.45(2H,t), <tb> <SEP> 4.10(2H,t), <SEP> 5.90(1H,s), <SEP> 6.25(1H,br,s), <SEP> 7.07-7.77(4H,m) <tb> 5 <SEP> 3240 <SEP> 1692 <SEP> 1355 <SEP> 0.95-2.03(10H,m), <SEP> 1.06(6H,d), <SEP> 2.37, <SEP> 3.67(3H <SEP> x <SEP> 2,s), <SEP> 2.89(1H,m), <SEP> 3.33(3H,m), <tb> <SEP> 4.04(2H,t), <SEP> 5.90(1H,s), <SEP> 6.68(1H,br,s), <SEP> 7.10-7.77(4H,m) <tb> 6 <SEP> 3430 <SEP> 1690 <SEP> 1355 <SEP> 1.01-2.13(16H,m), <SEP> 2.36, <SEP> 3.66(3H <SEP> x <SEP> 2,s), <SEP> 2.58-3.20(1H,m), <SEP> 3.28-4.33(3H,m), <tb> <SEP> 5.91(1H,s), <SEP> 6.26(1H,br,s), <SEP> 7.03-7.77(4H,m) <tb> 7 <SEP> 2570- <SEP> 1685 <SEP> 1365a) <SEP> 1.01-3.37(20H,m), <SEP> 2.33, <SEP> 3.65(3H <SEP> x <SEP> 2,s), <SEP> 3.50(2H,t), <SEP> 3.80-4.33(2H,m), <SEP> 5.92(1H,s), <tb> <SEP> 2690 <SEP> 6.90(1H,br,s), <SEP> 7.07-7.73(4H,m) <tb> 8 <SEP> 3250 <SEP> 1688 <SEP> 1360 <SEP> 0.93-2.17(12H,m), <SEP> 2.33, <SEP> 3.68(3H <SEP> x <SEP> 2,s), <SEP> 2.67-3.13(1H,m), <SEP> 3.47-4.27(5H,m), <tb> <SEP> 5.93(1H,s), <SEP> 7.00-7.87(5H,m) <tb> 9 <SEP> 2300 <SEP> 1730 <SEP> 1378b) <SEP> 1.05-1.93(8H,m), <SEP> 2.33, <SEP> 3.63(3H <SEP> x <SEP> 2,s), <SEP> 2.63-3.12(1H,m), <SEP> 3.77-4.47(4H,m), <tb> <SEP> 1700 <SEP> 5.95(1H,s), <SEP> 6.70-7.78(4H,m) <tb> Table 5 (No. 2) EMI32.1 <SEP> IR <SEP> (#maxcm-1) <SEP> NMR <SEP> (#ppmCDCl3)* <tb> Example <tb> No. <SEP> NH <SEP> CO <SEP> NO2 <tb> 10 <SEP> 2530 <SEP> 1700 <SEP> 1360a) <SEP> 1.22-2.80(9H,m), <SEP> 2.42, <SEP> 3.67(3H <SEP> x <SEP> 2,s), <SEP> 4.07, <SEP> 4.37(2H <SEP> x <SEP> 2,m), <SEP> 5.27(1H,s), <tb> <SEP> 7.05(1H,br,s), <SEP> 7.05-8.08(9H,m) <tb> 11 <SEP> 2530- <SEP> 1679 <SEP> 1357a) <SEP> 0.83-2.77(11H,m), <SEP> 2.35, <SEP> 3.63(3H <SEP> x <SEP> 2,s), <SEP> 3.92-4.08(2H,m), <SEP> 4.17-4.50(2H,m), <tb> <SEP> 2650 <SEP> 3.91(1H,s), <SEP> 6.90(1H,br,s), <SEP> 6.75-7.70(9H,m) <tb> 12 <SEP> 2300 <SEP> 1702 <SEP> 1378b) <SEP> 1.00-3.20(1H,m), <SEP> 2.07, <SEP> 2.35, <SEP> 3-65(3H <SEP> x <SEP> 3,s), <SEP> 3.83-4.33(2H,m), <SEP> 5.90(1H,s), <tb> <SEP> 7.00-8.03(4H,m) <tb> 13 <SEP> 3430 <SEP> 1690 <SEP> 1355 <SEP> 1.10-2.58(11H,m), <SEP> 2.22(6H,s), <SEP> 2.38, <SEP> 3.70(3H <SEP> x <SEP> 2,s), <SEP> 2.72-3.83(2H,m), <tb> <SEP> 3.57-4.30(2H,m), <SEP> 5.91(1H,s), <SEP> 6.95-7.81(4H,m) <tb> 14 <SEP> 3430 <SEP> 1685 <SEP> 1350 <SEP> 1.08-3.03(15H,m), <SEP> 2.30, <SEP> 3.58(3H <SEP> x <SEP> 2,s), <SEP> 3.50(2H,s), <SEP> 4.87-5.20(1H,m), <SEP> 6.02(1H,s), <tb> <SEP> 7.01-7.85(10H,m) <tb> 15 <SEP> 3430 <SEP> 1680 <SEP> 1350 <SEP> 1.12-3.00(17H,m), <SEP> 2.32, <SEP> 3.63(3H <SEP> x <SEP> 2,s), <SEP> 4.43-4.90(1H,m), <SEP> 6.21(1H,s), <tb> <SEP> 7.10-7.86(9H,m) <tb> 16 <SEP> 2570- <SEP> 1697 <SEP> 1357a) <SEP> 0.77-3.16(18H,m), <SEP> 2.34, <SEP> 3.63(3H <SEP> x <SEP> 2,s), <SEP> 3.75-4.07(2H,m), <SEP> 5.92(1H,s), <SEP> 6.98 <tb> <SEP> 2675 <SEP> (1H,br,s), <SEP> 7.07-7.73(4H,m) <tb> 17 <SEP> 2300 <SEP> 1733 <SEP> 1375b) <SEP> 1.10-2.00(8H,m), <SEP> 2.27, <SEP> 3.62(3H <SEP> x <SEP> 2,s), <SEP> 2.57-3.27(3H,m), <SEP> 3.87-4.50(2H,m), <tb> <SEP> 1700 <SEP> 5.93(1H,s), <SEP> 7.00-8.27(9H,m) <tb> Table 5 (No.3) EMI33.1 <SEP> IR <SEP> (#maxcm-1) <SEP> NMR <SEP> (#ppmCDCl3)* <tb> Example <tb> No. <SEP> NH <SEP> CO <SEP> NO2 <tb> 18 <SEP> 2370 <SEP> 1705 <SEP> 1360a) <SEP> 1.10-3.20(9H,m), <SEP> 2.29, <SEP> 3.67(3H <SEP> x <SEP> 3,s), <SEP> 2.73(2H,t), <SEP> 3.90-4.37(2H,m), <SEP> 5.88(1H,s), <tb> <SEP> 6.74(1H,br,s), <SEP> 6.99-7.73(8H,m) <tb> 19 <SEP> 2360 <SEP> 1699 <SEP> 1348a) <SEP> 1.11-3.18(9H,m), <SEP> 3.30, <SEP> 3.64(3H <SEP> x <SEP> 2,s), <SEP> 2.70(2H,t), <SEP> 3.82(6H,s), <SEP> 3.93-4.29(2H,m), <tb> <SEP> 5.90(1H,s), <SEP> 6.72(3H,s), <SEP> 6.83(1H,br,s), <SEP> 7.07-7.73(4H,m) <tb> 20 <SEP> 3430 <SEP> 1690 <SEP> 1350 <SEP> 1.10-2.77(9H,m), <SEP> 2.37, <SEP> 3.20, <SEP> 3.24, <SEP> 3.66(3H <SEP> x <SEP> 4,s), <SEP> 3.97-4.50(3H,m), <SEP> 5.22(1H,s) <tb> <SEP> 6.92(1H,br,s), <SEP> 7.12-8.08(9H,m) <tb> 21 <SEP> 3425 <SEP> 1675 <SEP> 1340 <SEP> 0.37-2.70(27H,m), <SEP> 4.67(1H,m), <SEP> 2.38, <SEP> 2.45, <SEP> 3.66(3H <SEP> x <SEP> 3,s), <SEP> 5.20, <SEP> 5.27(1H,2s), <SEP> 6.80, <tb> <SEP> 6.93(1H,2 <SEP> br,s), <SEP> 7.20-8.12(4H,m). <tb> 22 <SEP> 2700 <SEP> 1694 <SEP> 1352a) <SEP> 1.0-1.93(8H,m), <SEP> 2.3(3H,s), <SEP> 2.67-3.23(3H,m), <SEP> 3.6(3H,s), <SEP> 3.85-4.33(2H,m), <SEP> 5.85(1H,s) <tb> <SEP> 6.87-8.03(9H,m) <tb> 23 <SEP> 2670 <SEP> 1705 <SEP> 1363a) <SEP> 1.0-3.20(9H,m), <SEP> 1.23(3H <SEP> x <SEP> 2,d), <SEP> 2.37, <SEP> 3.67(3H <SEP> x <SEP> 2,s), <SEP> 2.56(2H,t), <SEP> 2.93(3H,sep), <tb> <SEP> 3.83-4.30(2H,m), <SEP> 5.90(1H,s), <SEP> 7.0(1H,br,s), <SEP> 7.12-7.77(4H,m) <tb> 24 <SEP> 2480 <SEP> 1701 <SEP> 1359a) <SEP> 1.03-3.30(18H,m), <SEP> 2.38, <SEP> 3.68(3H <SEP> x <SEP> 2,s), <SEP> 2.58(2H,t), <SEP> 3.87-4.33(2H,m), <SEP> 5.91(1H,s), <tb> <SEP> 6.88(1H,br,s), <SEP> 7.13-7.77(4H,m) <tb> 25 <SEP> 2320 <SEP> 1700 <SEP> 1358a) <SEP> 0.77-3.10(20H,m), <SEP> 2.33, <SEP> 3.62(3H <SEP> x <SEP> 2,s), <SEP> 3.73-4.17(2H,m), <SEP> 5.90(1h,s), <SEP> 6.83 <tb> <SEP> (1H,br,s), <SEP> 7.07-7.73(4H,m) <tb> Tanble 5 (No. 4) EMI34.1 <SEP> IR <SEP> (#maxcm-1) <SEP> NMR <SEP> (#ppmCDCl3)* <tb> Example <tb> No. <SEP> NH <SEP> CO <SEP> NO2 <tb> 26 <SEP> 2450 <SEP> 1701 <SEP> 1355a) <SEP> 0.53-2.30(19H,m), <SEP> 2.38(3H,s), <SEP> 2.71-3.20(1H,m), <SEP> 3.50-4.28(2H,m), <SEP> 3.68(3H,s), <tb> <SEP> 5.94(1H,s), <SEP> 6.52(1H,br,s), <SEP> 7.10-0.81(4H,m) <tb> 27 <SEP> 2530 <SEP> 1683 <SEP> 1358 <SEP> 1.03-3.17(17H,m), <SEP> 2.32, <SEP> 3.62(3H <SEP> x <SEP> 2,s), <SEP> 5.03(1H,m), <SEP> 6.03(1H,s), <SEP> 6.90(1H,br,s), <tb> <SEP> 7.10-7.82(4H,m) <tb> 28 <SEP> 2525 <SEP> 1702 <SEP> 1355a) <SEP> 0.9-3.13(19H,m), <SEP> 2.36, <SEP> 3.63(3H <SEP> x <SEP> 2,s), <SEP> 4.62(1H,m), <SEP> 6.03(1H,s), <SEP> 6.82(1H,br,s), <tb> <SEP> 7.10-7.84(4H,m) <tb> a): Hydrochloride, b): Oxalate o: Data of NMR are shown as those on free bases. Table 5 (No. 5) EMI35.1 Example <SEP> IR <SEP> (&gamma;maxcm-1) <SEP> NMR(#ppmCDCl3)* <tb> <SEP> No. <SEP> NH <SEP> CO <SEP> NO2 <tb> <SEP> 3420 <SEP> 1.15-2.0(8H,m), <SEP> 2.35(3H,m), <SEP> 2.60(1H,m), <SEP> 2.70-2.93(2H,m), <SEP> 3.66(3H,s), <SEP> 4.04-4.37 <tb> <SEP> 29 <SEP> 3270 <SEP> 1685 <SEP> 1350 <SEP> (2H,m), <SEP> 5.12(1H,s), <SEP> 6.35(1H,s), <SEP> 6.99-8.01(8H,m) <tb> <SEP> 3420 <SEP> 1.15-1.72(8H,m), <SEP> 2.36(3H,s), <SEP> 2.58(1H,m), <SEP> 2.83(2H,m), <SEP> 3.67(3H,s), <SEP> 3.85(6H,s), <tb> <SEP> 30 <SEP> 3280 <SEP> 1685 <SEP> 1350 <SEP> 4.24(2H,m), <SEP> 5.20(1H,s), <SEP> 6.65-8.05(8H,m) <tb> <SEP> 31 <SEP> 2670 <SEP> 1700 <SEP> 1375a) <SEP> 1.07-3.32(9H,m), <SEP> 2.30(3H,s), <SEP> 2.75(2H,t), <SEP> 3.67(3H,a), <SEP> 4.17(2H,t), <SEP> 5.90(1H,s), <tb> <SEP> 6.83-7.80(4H,m), <SEP> 8.27(1H,s) <tb> <SEP> 32 <SEP> 2380 <SEP> 1713 <SEP> 1355a) <SEP> 1.07-2.0(8H,m), <SEP> 2.27(3H,s), <SEP> 2.72(2H,t), <SEP> 2.72-3.18(1H,m), <SEP> 3.62(3H,s), <SEP> 5.87(1H,s), <tb> <SEP> 6.83-7.83(8H,m) <tb> <SEP> 33 <SEP> 2680 <SEP> 1715 <SEP> 1338a) <SEP> 1.07-2.13(8H,m), <SEP> 2.25(3H,s), <SEP> 2.55-3.20(1H,m), <SEP> 2.83(2H,t), <SEP> 3.62(3H,s), <SEP> 4.17(2H,t), <tb> <SEP> 5.87(1H,s), <SEP> 6.97-7.83(8H,m) <tb> EXAMPLE 34 Components for tablet Phenethyl=3-cyclopentyl-1,6-dimethyl-4-(2-nitrophenyl)-4, 7-dihydropyrazolo[3,4-b]pyridine-5-carboxylate 10 mg Corn starch 50 mg Gelatis 7.5 mg Avicel ---------------- 25 Mg Magnesium stearate 2.5 mg Total 95 mg These substances are formulated into a tablet. PREPARATION 1 Preparation of 2-methoxyethyl=2-nitrobenzylideneacetoacetate 6 EMI36.1 A solution of 4.80 g (30.0 mMol) of methoxyethylacetoacetate 5, 4.53 g (30.0 mMol) of 2-nitrobenzaldehyde 4, 1.0 al of acetic acid and 0.3 ml of piperidine in 25 ml of benzene is stirred at room temperature for 17 hours, and the mixture is ref fluxed for 2 hours in a condition of azeotropic distillation. The reaction mixture is washed with water, dried over magnesium sulfate, filtered, and evaporated. The residue is chromatographed on silica gel for purification to give 7.93 g (90.2X yield) of the titled compound 6 as an yellow oil [from the eluate with dichloromethane/ethyl acetate (95/5)]. NMR(CDC13) # Gppm: 2.23, 2.48(3H, 2s), 3.17-3.80(2H, m), 3.22, 3.40(3H, 2s), 4.08-4.53(2H, m), 7.33-8.33(5H, m). PREPARATIONs 2-30 EMI37.1 wherein R1 has the same meaning as defined above. A solution of the compound (ME) and a compound (M) in a solvent is allowed to react in the presence of an organic base at room temperature or under heating, and then ref fluxed if needed. The reaction fixture is washed with water, dried, filtered, and evaporated. According to the requisition, the resulting residue is subjected to recrystallization or chromatography on silica gel in order to purify. Each of the compounds (I ) listed in the following Table 6 can be prepared in the above-depicted manner The yield for a compound (I ) is listed in Table 6. The Process for production of the starting substances (IX) is depicted over the top of Table 6, the yield of which is also listed in Table 6. In addition, the detailes of the reaction conditions for the above reaction (Preparations 2-25) are summarized i Table 7. Data of pelting point and NMR spectrum on each of the compounds (I ) and the starting substances (IX) are summarized in Table 8. EMI39.1 Table 6 (No.1.) (VIII) EMI39.2 <tb> )repn. <SEP> Yield <SEP> of <SEP> Position <SEP> Yield <SEP> of <SEP> I <tb> <SEP> repn. <SEP> RZ <SEP> (X) <SEP> (%) <SEP> of <SEP> (ff) <SEP> ( <SEP> % <SEP> ) <tb> <SEP> -N02 <tb> <SEP> 2 <SEP> -CH2CH20CH3 <SEP> Compd. <SEP> '3 <SEP> 88.4 <tb> <SEP> marketed <tb> <SEP> 3 <SEP> CH2CH2CH20CIf3 <SEP> 72-7 <SEP> 2 <SEP> 50-7 <tb> <SEP> 3 <tb> <SEP> 4 <SEP> -CBZCRZO-a <SEP> 68.1 <SEP> n <SEP> 84.0 <tb> <SEP> l <tb> <SEP> 5 <SEP> g <SEP> -CH2CH20--0 <SEP> zo <SEP> 94.1 <SEP> . <SEP> 91.6 <tb> <SEP> I <tb> <SEP> 6 <SEP> -CH21 <SEP> 74.6 <SEP> n <SEP> 794 <tb> <SEP> 7 <SEP> -C2CHiO- <SEP> 865 <SEP> n <SEP> 94.4 <tb> <SEP> g <SEP> -CH2CH2SCH3 <SEP> 25.1 <SEP> 2 <SEP> 86.7 <tb> <SEP> 10 <SEP> | <SEP> CE2CE2CK2NEE3 <SEP> 79.0 <SEP> 53.1 <tb> <SEP> 3 <tb> <SEP> 11 <SEP> zoN-CH2 <SEP> 4 <SEP> 95.0 <SEP> n <SEP> 84.6 <tb> <SEP> 12 <SEP> 4 <SEP> -CH2 <SEP> 4 <SEP> 81.0 <SEP> n <SEP> 62.2 <tb> <SEP> u <tb> <SEP> 13 <SEP> 1 <SEP> ¯(Cz2)4Cz3 <SEP> 77.0 <SEP> a9.O <tb> <SEP> 14 <SEP> -CH2CH2- <SEP> 89.3 <SEP> n <SEP> n <SEP> 1 <SEP> 88.2 <tb> <SEP> 15 <SEP> -CH2CH2--C1 <SEP> 958 <SEP> " <SEP> 93.8 <tb> <SEP> - <SEP> $1.0 <tb> Table 6 (No.2) EMI40.1 Propn <SEP> R' <SEP> Yield <SEP> of <SEP> Position <SEP> Yield <SEP> of <tb> <SEP> No. <SEP> (IX) <SEP> (%) <SEP> of <SEP> (II) <SEP> (%) <tb> <SEP> NO2 <tb> <SEP> 16 <SEP> -CH2CH2-#-OCH3 <SEP> <SEP> 92.9 <SEP> 2 <SEP> 96.8 <tb> <SEP> OCH3 <tb> <SEP> 17 <SEP> -CHCH2-# <SEP> <SEP> 89.6 <SEP> 3 <SEP> 87.5 <tb> <SEP> 18 <SEP> -#-CH3 <SEP> <SEP> 89.4 <SEP> 3 <SEP> 71.2 <tb> <SEP> 19 <SEP> -CH2CH2S-# <SEP> 99.6 <SEP> 2 <SEP> 84.2 <tb> <SEP> CH3 <tb> <SEP> 20 <SEP> -CH2CH2S-CH <SEP> 96.6 <SEP> " <SEP> 93.2 <tb> <SEP> CH3 <tb> <SEP> 21 <SEP> -CH2CH2-S-# <SEP> 92.1 <SEP> " <SEP> 92.4 <tb> <SEP> 22 <SEP> -CH2CH2-# <SEP> <SEP> 96.6 <SEP> " <SEP> 97.4 <tb> 23 <SEP> -CH2-# <SEP> <SEP> 94.5 <SEP> " <SEP> 85.5 <tb> <SEP> 24 <SEP> -# <SEP> <SEP> 92.9 <SEP> " <SEP> 97.7 <tb> <SEP> 25 <SEP> -# <SEP> <SEP> 93.5 <SEP> " <SEP> 97.3 <tb> Disclosed in (IX)-18: F.Korts, F.Yuesten, Liebigs Ann., 647, 18(1961) # Material for (IX)-II EMI40.2 Disclosed in E.Jaeger, J.H.Biel, J.Org. Chem. 30, 740 (1965) Ph=Phenyl Table 6 (No.3) EMI41.1 Prepn. <SEP> RÚ <SEP> Yield <SEP> of <SEP> Position <SEP> Yield <SEP> of <tb> <SEP> No. <SEP> (IX) <SEP> (%) <SEP> of <SEP> (II) <SEP> (%) <tb> <SEP> -NO2 <tb> <SEP> 26 <SEP> ##-Cl <SEP> vide <SEP> supra <SEP> 3 <SEP> 98.0 <tb> <SEP> 27 <SEP> ##-OMe <SEP> vide <SEP> supra <SEP> 3 <SEP> 90.4 <tb> <SEP> OMe <tb> <SEP> 28 <SEP> ##-Cl <SEP> 90.6 <SEP> 2 <SEP> 93.1 <tb> <SEP> Cl <tb> <SEP> 29 <SEP> ##-Br <SEP> 98.1 <SEP> 2 <SEP> 76.5 <tb> <SEP> 30 <SEP> ## <SEP> 97.2 <SEP> 2 <SEP> 54.1 <tb> <SEP> CF3 <tb> EMI42.1 # EMI42.2 Prepn. <SEP> Amoundt <SEP> used <SEP> g <SEP> (mmol.) <SEP> Solvent <SEP> Reation <SEP> Reaction <tb> <SEP> No. <SEP> Compd.(VII) <SEP> Compd.(IX) <SEP> (ml) <SEP> Temp. <SEP> Time <tb> <SEP> ( C) <SEP> (hrs.) <tb> <SEP> 2 <SEP> 4.53(30.0) <SEP> 4.80(30.0) <SEP> benzene <SEP> (25) <SEP> r.t. <SEP> 21 <tb> <SEP> F(0.1), <SEP> AcOH(0.3) <tb> 3 <SEP> 2.04(13.5) <SEP> 2.72(13.4) <SEP> benzene <SEP> (5) <SEP> r.t. <SEP> 100 <tb> <SEP> F(0.1), <SEP> AcOH(0.2) <SEP> reflux <SEP> 1 <tb> <SEP> 4 <SEP> 0.30(1.96) <SEP> 0.42(1.96) <SEP> benzene <SEP> (2) <SEP> r.t. <SEP> 72 <tb> <SEP> F(0.004), <SEP> AcOH(0.01) <SEP> reflux <SEP> 2 <tb> <SEP> 5 <SEP> 1.51(10.0) <SEP> 2.28(10.0) <SEP> benzene <SEP> (5) <SEP> r.t. <SEP> 72 <tb> <SEP> F(0.05), <SEP> AcOH(0.2) <SEP> reflux <SEP> 3 <tb> <SEP> 6 <SEP> 4.53(30.0) <SEP> 5.58(30.0) <SEP> benzene <SEP> (10) <SEP> r.t. <SEP> 72 <tb> <SEP> F(0.1), <SEP> AcOH(0.4) <tb> <SEP> 7 <SEP> 4.76(31.5) <SEP> 7.0(31.5) <SEP> benzene <SEP> (10) <SEP> 40 <SEP> 100 <tb> <SEP> F(0.05), <SEP> AcOH(0.2) <SEP> reflux <SEP> 2 <tb> <SEP> 8 <SEP> " <SEP> " <SEP> " <SEP> " <SEP> " <tb> <SEP> 9 <SEP> 3.78(25.0) <SEP> 4.4(25.0) <SEP> benzene <SEP> (5) <SEP> r.t. <SEP> 72 <tb> <SEP> F(0.1), <SEP> AcOH(0.4) <tb> <SEP> 10 <SEP> 4.53(30.0) <SEP> 5.62(30.0) <SEP> benzene <SEP> (10) <SEP> r.t. <SEP> 72 <tb> <SEP> F(0.1), <SEP> AcOH(0.4) <tb> <SEP> 11 <SEP> 0.91(6.01) <SEP> 1.57(6.01) <SEP> benzene <SEP> (3) <SEP> r.t. <SEP> 48 <tb> <SEP> F(0.01), <SEP> AcOH(0.04) <SEP> reflux <SEP> 1 <tb> <SEP> 12 <SEP> 1.14(7.57) <SEP> 2.08(7.57) <SEP> benzene <SEP> (4) <SEP> reflux <SEP> 4 <tb> F(0.01), <SEP> AcOH(0.04) <tb> <SEP> 13 <SEP> 6.14(40.6) <SEP> 7.00(40.6) <SEP> benzene <SEP> (10) <SEP> 40 <SEP> 100 <tb> <SEP> F(0.05), <SEP> AcOH(0.2) <SEP> reflux <SEP> 2 <tb> 14 <SEP> 4.53(30.0) <SEP> 6.18(30.0) <SEP> benzene <SEP> (10) <SEP> r.t. <SEP> 72 <tb> <SEP> F(0.1), <SEP> AcOH(0.4) <SEP> reflux <SEP> 3 <tb> Table 7 (No.2) EMI43.1 Prepn. <SEP> Amoundt <SEP> used <SEP> g <SEP> (mmol.) <SEP> Solvent <SEP> Reation <SEP> Reaction <tb> <SEP> No. <SEP> Compd.(VII) <SEP> Compd.(IX) <SEP> (ml) <SEP> Temp. <SEP> Time <tb> <SEP> ( C) <SEP> (hrs.) <tb> <SEP> 15 <SEP> 1.51(10.0) <SEP> 2.41(10.0) <SEP> benzene <SEP> (5) <SEP> r.t. <SEP> 72 <tb> <SEP> P(0.05), <SEP> AcOH(0.2) <SEP> reflux <SEP> 2 <tb> <SEP> 16 <SEP> 1.51(10.0) <SEP> 2.66(10.0) <SEP> benzene <SEP> (5) <SEP> r.t. <SEP> 72 <tb> <SEP> P(0.05), <SEP> AcOH(0.2) <SEP> reflux <SEP> 3 <tb> <SEP> 17 <SEP> 1.62(10.7) <SEP> 2.53(10.7) <SEP> benzene <SEP> (2) <SEP> r.t. <SEP> 72 <tb> <SEP> P(0.02), <SEP> AcOH(0.1) <SEP> reflux <SEP> 7 <tb> <SEP> 18 <SEP> 4.0(26.5) <SEP> 6.38(26.5) <SEP> benzene <SEP> (10) <SEP> r.t. <SEP> 72 <tb> <SEP> P(0.05), <SEP> AcOH(0.2) <SEP> reflux <SEP> 7 <tb> <SEP> 19 <SEP> 3.0(20.0) <SEP> 4.76(20.0) <SEP> benzene <SEP> (20) <SEP> r.t. <SEP> 16 <tb> <SEP> P(0.1), <SEP> AcOH(0.2) <SEP> reflux <SEP> 2 <tb> <SEP> 20 <SEP> 4.89(32.3) <SEP> 6.6(32.3) <SEP> benzene <SEP> (20) <SEP> r.t. <SEP> 16 <tb> <SEP> P(0.15), <SEP> AcOH(0.3) <SEP> reflux <SEP> 1 <tb> <SEP> 21 <SEP> 4.34(29.1) <SEP> 6.7(29.1) <SEP> benzene <SEP> (20) <SEP> r.t. <SEP> 16 <tb> <SEP> P(0.15), <SEP> AcOH(0.3) <SEP> reflux <SEP> 1 <tb> <SEP> 22 <SEP> 3.58(23.7) <SEP> 4.7(23.7) <SEP> benzene <SEP> (20) <SEP> r.t. <SEP> 16 <tb> <SEP> P(0.3), <SEP> AcOH(0.6) <SEP> reflux <SEP> 1 <tb> <SEP> 23 <SEP> 4.53(30.0) <SEP> 5.95(30.0) <SEP> benzene <SEP> (10) <SEP> r.t. <SEP> 16 <tb> <SEP> P(0.3), <SEP> AcOH(0.6) <SEP> reflux <SEP> 1 <tb> <SEP> 24 <SEP> 2.66(17.6) <SEP> 3.0(17.6) <SEP> benzene <SEP> (6) <SEP> r.t. <SEP> 16 <tb> <SEP> P(0.05), <SEP> AcOH(0.2) <SEP> reflux <SEP> 2 <tb> <SEP> 25 <SEP> 2.46(16.3) <SEP> 3.0(16.3) <SEP> benzene <SEP> (6) <SEP> r.t. <SEP> 16 <tb> <SEP> P(0.05), <SEP> AcOH(0.2) <SEP> reflux <SEP> 2 <tb> Table 7 (No.3) EMI44.1 Prepn. <SEP> Amount <SEP> used <SEP> g(mmol.) <SEP> Solvent <SEP> Reaction <SEP> Reaction <tb> <SEP> No. <SEP> Compd. <SEP> Compd. <SEP> (ml) <SEP> Temp. <SEP> Time <tb> <SEP> (VIII) <SEP> (IX) <SEP> ( C) <SEP> (hrs.) <tb> <SEP> 26 <SEP> 2.78(18.38) <SEP> 4.42(18.37) <SEP> benzene <SEP> (9) <SEP> r.t. <SEP> 96 <tb> <SEP> P(0.036), <SEP> AcOH(0.1) <SEP> reflux <SEP> 2 <tb> <SEP> 27 <SEP> 1.0(6.64) <SEP> 1.77(6.64) <SEP> benzene <SEP> (4) <SEP> r.t. <SEP> 96 <tb> <SEP> P(0.013), <SEP> AcOH(0.038) <SEP> reflux <SEP> 2 <tb> <SEP> 28 <SEP> 1.51(10.0) <SEP> 2.75(10.0) <SEP> benzene <SEP> (10) <SEP> r.t. <SEP> 20 <tb> <SEP> P(0.1), <SEP> AcOH(1.0) <SEP> reflux <SEP> 2 <tb> <SEP> 29 <SEP> 1.51(10.0) <SEP> 2.85(10.0) <SEP> benzene <SEP> (10) <SEP> r.t. <SEP> 20 <tb> <SEP> P(0.1), <SEP> AcOH(1.0) <SEP> reflux <SEP> 2 <tb> <SEP> 30 <SEP> 1.51(10.0) <SEP> 2.74(10.0) <SEP> benzene <SEP> (10) <SEP> r.t. <SEP> 20 <tb> <SEP> P(0.1), <SEP> AcOH(1.0) <SEP> reflux <SEP> 2 <tb> *P: Piperidine, AcOH: Acetic acid, r.t.: room temperature Table 8(No.1) CH3COCH2COORÚ (IX) EMI45.1 Prepn. <SEP> Boiling <SEP> point <SEP> NMR <SEP> (#ppmCDCl3) <tb> <SEP> No. <SEP> C <SEP> (mmHg) <tb> (IX)-3 <SEP> 90-91 <SEP> (0.6) <SEP> 1.12(6H,d), <SEP> 1.93(2H,m), <SEP> 2.55(3H,s), <SEP> 3.33-4.02(3H,m), <SEP> 3.45(2H,s), <SEP> 4.23(2H,t) <tb> <SEP> 4 <SEP> 96-100 <SEP> (0,1) <SEP> 1.15-1.90(8H,m), <SEP> 2.27(3H,s), <SEP> 3.36-4.47(5H,m), <SEP> 3.47(2H,s) <tb> <SEP> 5 <SEP> 118-120 <SEP> (0.4) <SEP> 1.15-2.07(10H,m). <SEP> 2.26(3H,s), <SEP> 3.25(1H,m), <SEP> 3.45(2H,s), <SEP> 3.63, <SEP> 4.26(2H <SEP> x <SEP> 2,s) <tb> <SEP> 6 <SEP> 95-100 <SEP> (0.9) <SEP> 1.33-2.17(4H,m), <SEP> 2.27(3H,s), <SEP> 3.50(2H,s), <SEP> 3.53-4.33(4H,m) <tb> <SEP> 7,8 <SEP> 140-143 <SEP> (0.7) <SEP> 2.20(3H,s), <SEP> 3.43(2H,s), <SEP> 4.03-4.60(4H,m), <SEP> 6.73-7.43(5H,m) <tb> <SEP> 9 <SEP> 160-162 <SEP> (25) <SEP> 2.13, <SEP> 2.27(3H <SEP> x <SEP> 2,s), <SEP> 2.72(2H,t), <SEP> 3.45(2H,s), <SEP> 4.28(2H,t) <tb> <SEP> 10 <SEP> 138-141 <SEP> (23) <SEP> 1.40-2.98(4H,m), <SEP> 2.20(6H,s), <SEP> 2.23(3H,s), <SEP> 3.45(2H,s), <SEP> 4.18(2H,t) <tb> <SEP> 11 <SEP> oil <SEP> 1.63-2.98(6H,m), <SEP> 2.23(3H,s), <SEP> 3.42, <SEP> 3.63(2H <SEP> x <SEP> 2,s), <SEP> 5.24(1H,m), <SEP> 7.31(5H,s) <tb> <SEP> 12 <SEP> oil <SEP> 1.48-2.82(8H,m), <SEP> 2.23(3H,s), <SEP> 3.40, <SEP> 3.47(2H <SEP> x <SEP> 2,s), <SEP> 4.83(1H,m), <SEP> 7.27(5H,s) <tb> Table 8 (No.2) EMI46.1 Prepn. <SEP> Boiling <SEP> point <SEP> NMR <SEP> (#ppmCDCl3) <tb> <SEP> No. <SEP> C <SEP> (mmHg) <tb> (IX)-13 <SEP> 105-111 <SEP> (8) <SEP> 0.67-2.17(9H,m), <SEP> 2.27(3H,s), <SEP> 3.45(2H,s), <SEP> 4.13(2H,t) <tb> <SEP> 14 <SEP> 110-115 <SEP> (0.8) <SEP> 2.15(3H,s), <SEP> 2.93(2H,t), <SEP> 3.38(2H,s), <SEP> 4.33(2H,t), <SEP> 7.23(5H,s) <tb> <SEP> 15 <SEP> 155-158 <SEP> (0.7) <SEP> 1.18(3H,s), <SEP> 2.90(2H,t), <SEP> 3.39(2H,s), <SEP> 4.30(2H,t), <SEP> 7.10, <SEP> 7.26(2H <SEP> x <SEP> 2,d) <tb> <SEP> 16 <SEP> 182-185 <SEP> (0.8) <SEP> 2.19, <SEP> 3.82, <SEP> 3.85(3H <SEP> x <SEP> 3,s), <SEP> 2.88(2H,t), <SEP> 3.40(2H,s), <SEP> 3.42(2H,t), <SEP> 6.75(3H,m) <tb> <SEP> 17 <SEP> oil <SEP> 2.23, <SEP> 3.23(3H <SEP> x <SEP> 2,s), <SEP> 3.46(2H,s), <SEP> 4.37(3H,m), <SEP> 7.28(5H,s) <tb> <SEP> 18 <SEP> 95-101 <SEP> (0.3) <SEP> 0.62-2.35(18H,m), <SEP> 4.73(1H,m), <SEP> 2.35(3H,s), <SEP> 3.42(2H,s) <tb> <SEP> 19 <SEP> oil <SEP> 2.18(3H,s), <SEP> 3.08(2H,t), <SEP> 3.33(3H,s), <SEP> 4.20(2H,t), <SEP> 6.97-7.37(5H,m) <tb> <SEP> 20 <SEP> oil <SEP> 1.25(3H <SEP> x <SEP> 2,d), <SEP> 2.27(3H,s), <SEP> 2.75(2H,t), <SEP> 3.02(1H,q), <SEP> 3.43(2H,s), <SEP> 4.23(2H,t) <tb> <SEP> 21 <SEP> oil <SEP> 1.13-2.23(8H,m), <SEP> 2.47(3H,s), <SEP> 3.73(2H,t), <SEP> 2.93-3.27(1H,m), <SEP> 3.43(2H,s), <SEP> 4,23(2H,t) <tb> <SEP> 22 <SEP> oil <SEP> 1.03-2.0(11H,m), <SEP> 2.23(3H,s), <SEP> 3.4(2H,s), <SEP> 4.3(2H,t) <tb> Table 8 (No.3) EMI47.1 Prepn. <SEP> C <SEP> (mmHg) <SEP> NMR <SEP> (#ppmCDCl3) <tb> <SEP> No. <SEP> Boiling <SEP> point <tb> (IX)-23 <SEP> oil <SEP> 0.67-2.03(11H,m), <SEP> 2.2(3H,s), <SEP> 3.40(2H,s), <SEP> 3.95(2H,d) <tb> <SEP> 24 <SEP> 103-106 <SEP> (6) <SEP> 0.96-2.10(8H,m), <SEP> 2.28(3H,s), <SEP> 3.43(2H,s), <SEP> 5.25(1H,m) <tb> <SEP> 25 <SEP> 116-119 <SEP> (6) <SEP> 0.97-2.04(10H,m), <SEP> 2.25(3H,s), <SEP> 3.42(2H,s), <SEP> 4.82(1H,m) <tb> Table 8 (No.4) EMI48.1 Prepn. <SEP> Boiling <SEP> point <SEP> NMR <SEP> (#ppmCDCl3) <tb> <SEP> No. <SEP> C <SEP> (mmHg) <tb> (IX)-26 <SEP> vide <SEP> supra <SEP> vide <SEP> supra <tb> <SEP> 27 <SEP> vide <SEP> supra <SEP> vide <SEP> supra <tb> <SEP> 28 <SEP> oil <SEP> 2.18(3H,m), <SEP> 2.90(2H,t), <SEP> 3.40(2H,s), <SEP> 4.30(2H,t), <SEP> 6.90-7.43(3H,m) <tb> <SEP> 29 <SEP> oil <SEP> 2.18(3H,s), <SEP> 2.88(2H,t), <SEP> 3.40(2H,s), <SEP> 4.32(2H,t), <SEP> 6.93-7.53(4H,m) <tb> <SEP> 30 <SEP> oil <SEP> 2.20(3H,s), <SEP> 3.02(2H,t), <SEP> 3.42(2H,s), <SEP> 4.37(2H,t), <SEP> 7.43(4H,s) <tb> EMI49.1 Table 8 (No.5) EMI49.2 Prepn. <SEP> Boiling <SEP> point <SEP> NMR <SEP> (#ppmCDCl3) <tb> <SEP> No. <SEP> ( C) <tb> (II)-2 <SEP> mp.73-45 C <SEP> 2.43, <SEP> 6.28(3H <SEP> x <SEP> 2,s), <SEP> 3.50-3.75(2H,m), <SEP> 4.30-4.55(2H,m), <SEP> 7.33-8.33(5H,m) <tb> <SEP> 3 <SEP> oil <SEP> 1.08(6H,d), <SEP> 4.52-2.07(2H,m), <SEP> 2.47(3H,s), <SEP> 3.12-4.48(5H,m), <SEP> 7.27-8.25(5H,m) <tb> <SEP> 4 <SEP> oil <SEP> 1.07-1.84(8H,m), <SEP> 2.23, <SEP> 2.49(3H,2s), <SEP> 3.17-4.47(5H,m), <SEP> 7.36-8.31(5H,m) <tb> <SEP> 5 <SEP> oil <SEP> 0.77-2.10(10H,m), <SEP> 2.22, <SEP> 2.47(3H,2s), <SEP> 3.17(1H,m), <SEP> 3.43, <SEP> 3.72(2H,2t), <SEP> 4.17, <SEP> 4.42 <tb> <SEP> (2H,2t), <SEP> 7.27-8.30(5H,m) <tb> <SEP> 6 <SEP> oil <SEP> 1.03-2.17(4H,m), <SEP> 2.23, <SEP> 2.47(3H,2s), <SEP> 3.47-4.37(5H,m), <SEP> 7.23-8.36(5H,m) <tb> <SEP> 7 <SEP> oil <SEP> 2.18, <SEP> 2.42(3H,2s), <SEP> 3.70-4.70(4H,m), <SEP> 6.60-8.23(10H,m) <tb> <SEP> 8 <SEP> mp.127-161 C <SEP> 2.44(3H,s), <SEP> 4.18, <SEP> 4.65(2H <SEP> x <SEP> 2,t), <SEP> 6.72-8.33(10H,m) <tb> Table 8 (No.6) EMI50.1 Prepn. <SEP> melting <SEP> point <SEP> NMR <SEP> (#ppmCDCl3) <tb> <SEP> No. <SEP> ( C) <tb> (II)- <SEP> 9 <SEP> oil <SEP> 2.00, <SEP> 2.17(3H,2s), <SEP> 2.22, <SEP> 2.48(3H,2s), <SEP> 2.45, <SEP> 2.83(2H,2t), <SEP> 4.17, <SEP> 4.45(2H,2t) <tb> <SEP> 7.20-8.55(5H,m) <tb> <SEP> 10 <SEP> oil <SEP> 1.38-2.33(4H,m), <SEP> 2.13(6H,s), <SEP> 2.47(3H,s), <SEP> 4.05, <SEP> 4.33(2H,2t), <SEP> 7.25-8.33(5H,m) <tb> <SEP> 11 <SEP> oil <SEP> 1.36-3.06(6H,m), <SEP> 2.20, <SEP> 2.45(3H,2s), <SEP> 3.50, <SEP> 3.65(2H,2s), <SEP> 4.99-5.48(1H,m), <tb> <SEP> 7.16-8.27(10H,m) <tb> <SEP> 12 <SEP> oil <SEP> 1.09-2.85(8H,m), <SEP> 2.18, <SEP> 2.46(3H,2s), <SEP> 3.39, <SEP> 3.51(2H,2s), <SEP> 4.62-5.25(1H,m), <tb> <SEP> 7.07-8.41(10H,m) <tb> <SEP> 13 <SEP> oil <SEP> 0.63-2.02(9H,m), <SEP> 2.20, <SEP> 2.47(3H,2s), <SEP> 3.98, <SEP> 4.27(2H,2t), <SEP> 7.35-8.27(5H,m) <tb> <SEP> 14 <SEP> oil <SEP> 2.12, <SEP> 2.40(3H,2s), <SEP> 2.68, <SEP> 3.00(2H,2t), <SEP> 4.22, <SEP> 4.47(2H,2t), <SEP> 6.83-8.23(10H,m) <tb> <SEP> 15 <SEP> oil <SEP> 2.10, <SEP> 2.43(3H,2s), <SEP> 2.68, <SEP> 3.00(2H,2t), <SEP> 4.20, <SEP> 4.48(2H,2t), <SEP> 6.87-8.30(9H,m) <tb> <SEP> 16 <SEP> oil <SEP> 2.08, <SEP> 2.40(3H,2s), <SEP> 2.62, <SEP> 2.93(2H,2t), <SEP> 3.78, <SEP> 3.83, <SEP> 3.85(6H,3s), <SEP> 4.18, <SEP> 4.45(2H,2s) <tb> <SEP> 6.43-8.30(8H,m) <tb> Table 8 (NO.7) EMI51.1 Prepn. <SEP> melting <SEP> point <SEP> NMR <SEP> (#ppmCDCl3) <tb> <SEP> No. <SEP> ( C) <tb> (II)-17 <SEP> oil <SEP> 2.33, <SEP> 2.41(3H,2s), <SEP> 3.20, <SEP> 3.31(3H,2s), <SEP> 4.43(3H,m), <SEP> 7.28-8.27(10H,m) <tb> <SEP> 18 <SEP> oil <SEP> 0.48-2.48(16H,m), <SEP> 4.90(1H,m), <SEP> 2.38(3H,s), <SEP> 7.38-8.35(5H,m) <tb> <SEP> 19 <SEP> oil <SEP> 2.17, <SEP> 2.42(3H,s), <SEP> 2.82, <SEP> 3.18(2H,t), <SEP> 4.12, <SEP> 4.37(2H,t), <SEP> 7.0-8.23(10H,m), <tb> <SEP> 20 <SEP> oil <SEP> 1.2, <SEP> 1.32(3H <SEP> x <SEP> 2,d), <SEP> 2.23, <SEP> 2.5(3H,s), <SEP> 2.5, <SEP> 2.87(2H,t), <SEP> 2.77-3.17(1H,m), <SEP> 4.15, <tb> <SEP> 4.42(2H,t), <SEP> 7.23-8.33(5H,m) <tb> <SEP> 21 <SEP> oil <SEP> 1.07-2.11(8H,m), <SEP> 2.23, <SEP> 2.48(3H,s), <SEP> 2.52, <SEP> 2.87(2H,t), <SEP> 2.73-3.33(1H,m), <SEP> 4.17 <tb> <SEP> 4.4(2H,t), <SEP> 7.27-8.37(5H,m) <tb> <SEP> 22 <SEP> oil <SEP> 0.67-2.0(11H,m), <SEP> 2.2, <SEP> 2.45(3H,s), <SEP> 3.98, <SEP> 4.27(2H,t), <SEP> 7.23-8.3(5H,m) <tb> <SEP> 23 <SEP> oil <SEP> 0.5-2.0(11H,m), <SEP> 2.2, <SEP> 2.43(3H,s), <SEP> 3.8, <SEP> 4.07(2H,d), <SEP> 7.27-8.33(5H,m) <tb> <SEP> 24 <SEP> oil <SEP> 1.17-2.07(8H,m), <SEP> 2.20, <SEP> 2.47(3H,s), <SEP> 5.0-5.50(1H,m), <SEP> 7.30-8.29(4H,m) <tb> <SEP> 25 <SEP> oil <SEP> 0.83-2.17(10H,m), <SEP> 2.22, <SEP> 2.47(3H,s), <SEP> 4.57-5.17(1H,m), <SEP> 7.30-8.28(5H,m) <tb> Table 8 (No.8) EMI52.1 Prepn. <SEP> melting <SEP> point <SEP> NMR <SEP> (#ppmCDCl3) <tb> <SEP> No. <SEP> ( C) <tb> (II)-26 <SEP> oil <SEP> 2.25, <SEP> 2.37(3H,s), <SEP> 2.80-3.09(2H,m), <SEP> 4.35-4.57(2H,m), <SEP> 6.91-6.29(9H,m) <tb> <SEP> 27 <SEP> oil <SEP> 2.27, <SEP> 2.38(3H,s), <SEP> 2.78-3.04(2H,m), <SEP> 3.77, <SEP> 3.80(3H,s), <SEP> 3.83, <SEP> 3.87(3H), <SEP> 4.35-4.57(2H,m) <tb> <SEP> 6.59-8.28(8H,m) <tb> <SEP> 28 <SEP> oil <SEP> 2.12, <SEP> 2.43(3H,s), <SEP> 2.67, <SEP> 2.97(2H,t), <SEP> 4.20, <SEP> 4.45(2H,t), <SEP> 6.72-8.27(7H,m) <tb> <SEP> 29 <SEP> oil <SEP> 2.12, <SEP> 2.40(3H,s), <SEP> 2.69, <SEP> 2.95(2H,t), <SEP> 4.18, <SEP> 4.43(2H,t), <SEP> 6.73-8.27(9H,m) <tb> <SEP> 30 <SEP> oil <SEP> 2.10, <SEP> 2.40(3H,m), <SEP> 2.77, <SEP> 3.08(2H,t), <SEP> 4.23, <SEP> 4.48(2H,t), <SEP> 7.10-8.27(9H,m) <tb> PREPARATION 31 (i) Preparation of 3-cyclopentylcarbonylacetonitrile 9 EMI53.1 To 20 ml of tetrahydrofuran is added 15.6 ml (26 mMol) of butyl lithium in an atmosphere at -78µC, and 1.3 g (32 mMol) of acetonitrile is dropwisely added to the mixture over the period of 40 minutes. Two hours later, 3.43 g (25.9 mMol) of cyclopentylcarbonyl chloride 7 is further added dropwisely over a period of 40 minutes. The reaction mixture is, after being stirred for 2 hours, neutralized with 10 x hydrochloric acid and extracted with ether. The extract solution is dried over magnesium sulfate, filtered, and then evaporated. The resulting residue is subjected to column chromatography to give 2.91 g (80.8 % yield) of the titled compound 9 as an oil (from the chloroform layer). NMR(CDC1,) # Gppm: 1.43-2.2 (8H, m), 2.7-3.33 (1H, m), 3.53 (2H, s). Preparation of 5-amino-3-cyclopentyl-1-methylpyrazole II EMI54.1 To a solution of 13.21 g (96.3 mMol) of 3cyclopentylcarbonylacetonitrile 9 in 10 ml of dioxane is added 4.44 g (96.3 atfol) of methyldrazine 10 under ice-cooling, and the Mixture is stirred at room temperature for 17 hours. The reaction fixture is evaporated. The resulting residue is recrystallized fro. ethyl acetate/hexane (5/2) to give 12.9 g (80.8 X yield) of the titled compound 11 as colorless needles, mp. 149-150 C NMR(CDCl3) #ppm: 1.33-2.20(8H,m), 2.60-3.10(1H,m), 3.57 (5H, s), 5.32 (iR, s). PREPARATlONS 32 and 33 EMI54.2 wherein R2 and R3 have the same meanings as defined above respectively. A solution of compounds (N) and (V ) in a solvent is allowed to react at room temperature, then evaporated, and the resulting residue is purified by recrystallization, if needed. In the above-depicted manner, the compounds (m) can be prepared. Details of the reaction conditions are summarized in Table 9, and data such as yield, melting points, and NMR spectrum on the compounds are in Table 10. Table 9 EMI56.1 EMI56.2 Prepn. <SEP> Rê <SEP> R <SEP> Amount <SEP> used <SEP> g <SEP> (mmol.) <SEP> Solvent <SEP> Reaction <tb> <SEP> No. <SEP> Compd. <SEP> (IV) <SEP> Compd. <SEP> (V) <SEP> (ml) <SEP> Time <tb> <SEP> (hrs.) <tb> <SEP> 32 <SEP> CH3 <SEP> -# <SEP> 1.90(41.3) <SEP> 6.05(40.0) <SEP> ethanol <SEP> 24 <tb> <SEP> (10) <tb> <SEP> 33 <SEP> CH3 <SEP> -CH2-# <SEP> 1.43(31.0) <SEP> 4.60(30.4) <SEP> ethanol <SEP> 15 <tb> <SEP> (8) <tb> Table 10 EMI57.1 Prepn. <SEP> RÚ <SEP> R <SEP> Yield <SEP> Melting <SEP> Point <SEP> NMR: <SEP> #ppmCDCl3 <tb> <SEP> No. <SEP> (%) <SEP> ( C) <tb> <SEP> -CH3 <SEP> 71.7 <SEP> 173#174 <SEP> 0.90#277(11H,m), <tb> <SEP> 32 <SEP> -# <SEP> 3.43(2H,br,s), <tb> <SEP> 3.57(3H,s), <tb> <SEP> 5.32(1H,s) <tb> <SEP> -CH3 <SEP> 64.9 <SEP> 106#107 <SEP> 0.93#2.32(9H,m), <tb> <SEP> -CH2-# <SEP> 2.47(2H,m), <tb> <SEP> 33 <SEP> 3.51(3H,s), <tb> <SEP> 3.60(2H,br,s), <tb> <SEP> 5.28(1H,s) <tb>

Claims: What is claimed is: 1. A 4,7-dihydropyrazolo[3,4-b]pyridine derivative represented by the formula: EMI58.1 wherein Rl is alkyl of 5 or sore carbons, cycloalkyl which may be substituted, cycloalkylalkyl, alkoxyalkyl, cycloalkyloxyalkyl, aryloxyalkyl, alkylthioalkyl, cycloalkylthioalkyl, phenylthioalkyl, (cono- or di-alkylamino)alkyl, tetrahydrofurylalkyl, aralkyl which say be substituted by one or two substituents, N-benzylpyrrolidinyl, or N-benzylpiperidinyl : R2 is alkyl; and R3 is cycloalkyl or cycloalkylalkyl; and the acid addition salts thereof. 2. A compound claimed in dais 1, (3-thienyl)ethyl=3-cyclopentyl-1,6-dimethyl-4-(2-nitrophenyl)-4,7-dihydropyrazolo[3, 4-bjppridine-5-carboxylate. 3. A compound claimed in clain 1, isopropylthioethyl=3 cyclopentyl- 1, 6-diraethyl-4-(2-nitrophenyl)-4, 7dihydropyrazolo[3,4-b]pyridine-5-carboxylate. 4. A compound claimed in claim 1, cyclopentyloxyethyl=3 cyclopentyl- 1, 6-dimethyl-4-(2-nitrophenyl)-4, 7dihydropyrazolo[3, 4-b]pyridine-5-carboxylate. 5. A compound claimed in claim 1, methylthioethyl=3cyclopentyl-l, 6-dimethyl-4-(2-nitrophenyl)-4, 7dihydropyrazolo[3, 4-b] pyridine-S-carboxylate. 6. A compound claimed in claim 1, phenoxyethyl=3cyclopentyl-1, 6-dimethyl-4-(2-nitrophenyl)-4, 7dihydropyrazolo[3, 4-b]pyridine-5-carboxylate. 7. A compound claimed in claim 1, phenethyl=3-cyclopentyl1, 6-dimethyl-4-(2-nitrophenyl)-4, 7-dihydropyrazolo[3, 4-b]- pyridine-5-carboxylate. 8. A compound claimed in claim 1, methoxyethyl=3cyclohexyl-l, 6-dimethyl-4-(2-nitrophenyl)-4, 7dihydropyrazolo[3, 4-b]pyridine-5-carboxylate. 9. A compound claimed in claim 1, 2-tetrahydrofurylmethyl=3-cyclopentyl-1, 6-dimethyl-4-(2-nitrophenyl)-4, 7 dihydropyrazolo [ 3, 4-b] pyridine-S-carboxylate. 10. A compound claimed in claim 1, phenylthioethyl=3cyclopentyl-l, 6-dimethyl-4-(2-nitrophenyl)-4, 7dihydropyrazolo[3, 4-b]pyridine-5-carboxylate. 11. A compound claimed in claim 1, n-pentyl=3-cyclopentyl-1, 6-dimethyl-4-(2-nitrophenyl)-4, 7-dihydropyrazolo[3, 4-b]- pyridine-5-carboxylate. 12. A compound claimed in claim 1, cyclopentylthioethyl=3 Cyclopentyl-1, 6-dimethyl-4-(2-nitrophenyl)-4,7dihydropyrazolo[3, 4-b]pyridine-5-carboxylate. 13. A compound claimed in claim 1, cyclopentylethyl=3cyclopentyl-1, 6-dimethyl-4-(2-nitrophenyl)-4, 7dihydropyrazolo[3, 4-b]pyridine-5-carboxylate. 14. A process for production of 4,7-dihydropyrazolo[3,4-b]pyridine derivatives represented by the formula: EMI60.1 wherein Rt, R2 and R3 have the same meanings as defined above, respectively, which comprises reacting a compound represented by the formula: EMI60.2 wherein R1 has the same meaning as defined above, with a compound represented by the formula: EMI61.1 wherein R2 and R3 have the same meanings as defined above, respectively. 15. An agent for treating cardiovascular diseases, comprising at least one substance selected from 4,7dihydropyrazolo[3,4-b]pyridine derivatives represented by the formula: EMI61.2 wherein Rl, R2 and R3 have the same meanings as defined above, respectively, and the pharmaceutically acceptable acid addition salts thereof.

Inventors: ADACHI, IKUO, UEDA, MOTOHIKO, YAMAMORI, TERUO
Applicants: SHIONOGI & CO., LTD.
Application year: 1985
Main classification: C07D471
IPC codes: C07D471, A61P3, A61K31, A61P9, C07D211