PYRIMIDINE DERIVATIVES HAVING ANTITUMOR EFFECT

Abstract: A compound represented by the formula (I): wherein, for example, R 1 , R 2 , R 3 , and R 4 are each independently hydrogen atom, alkyl, and the like, R 5 and R 6 are each independently hydrogen atom, alkyl, and the like, R B and R C are each independently hydrogen atom, alkyl, and the like, X is -O-, -S-, and the like, Y is 5- membered heteroaryl-diyl and the like, Z is optionally substituted aryl and the like, their pharmaceutically acceptable salts, or their solvates.

Description: Technical Field The present invention relates to a novel pyrimidine derivative having an antitumor activity, a cytostatic activity, and an inhibitory activity against a signal derived from Ras oncogene products. Background Art The oncogene "ras" such as H-ras, K-ras, and N-ras is mutated and activated in many of neoplasms. The "Ras", the products of ras oncogene, strongly concerns tumorigenesis caused by acceleration of cell cycle and induction of expression of many of genes associated with a malignant conversion such as a vascular endothelial growth factor and type-IV collagenase. Especially, it is found that there is highly frequent ras mutation in solid tumor such as pancreatic cancer (> 80%), colon cancer (> 40%), and lung cancer (> 20%) which are difficult to be cured by using existing chemotherapeutics. Therefore, it is considered that Ras is one of the most important target molecules in the development of the chemotherapeutics against them. A farnesyl-protein-transferase (FPT) inhibitor (FPTI) is known as chemotherapeutics of which target are Ras (WO95/13059, WO95/25086, WO95/25092, WO95/34535, US5608067, and JP-A-7-112930). In the cells expressing activated Ras, the excess signals reach cell nucleus through some signaling pathways and some signal transmitter molecules such as MAPK (Mitogen Activated Protein Kinase) and PI3K (Phosphatidylinositol-3-Kinase). The signals activate the transcription factors such as AP1 (Activator Protein-1) and ETS (E26 transformation specific) in the cell nucleus and then they induce the expression of many genes related to malignant features through transcription activation element such as Ras Responsive Element (RRE). Therefore, it is possible to repress the malignant conversion of the cancer cells, when the signal transmission (a signal derived from ras oncogene products) is inhibited. Inhibitors of a signal derived from Ras oncogene products, of which basic structure is similar to that of the compounds of the present invention, are described in WO00/04014. Disclosure of Invention In the above situation, the inventors of the present invention have studied on the antitumor agent having an inhibitory activity against a signal derived from Ras oncogene products. The activation of gene expression through RRE is in proportion to a signal derived from Ras and the signal can be measured by the amount of its expression. The inventors of the present invention artificially made cells having activated Ras wherein expression of firefly luciferase gene, reporter gene, is regulated by RRE and carried out a screening of the inhibitors taking luciferase activity shown by the cells as an index of signals through Ras. As a result, the inventors of the present invention found that a series of pyrimidine derivatives have a strong inhibitory activity against a signal derived from Ras oncogene products. The present invention relates to I) a compound represented by the formula (I): wherein R 1 , R 2 , R 3 , and R 4 are each independently hydrogen atom, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted aralkyl, an optionally substituted non-aromatic heterocyclic group, acyl, optionally substituted amino, alkyloxy, hydroxy, cyano, or nitro; or R 1 and R 2 , R 3 and R 4 , and R 2 and R 3 each taken together with the adjacent nitrogen atom form the same or different 3- to 7- membered ring optionally containing O, N, or S, provided that R 1 and R 2 , and R 3 and R 4 do not form a ring when R 2 and R 3 taken together form a ring; R 5 and R 6 are each independently hydrogen atom, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted alkyloxy, alkylthio, optionally substituted alkyloxycarbonyl, optionally substituted aryl, optionally substituted heteroaryl, halogen, hydroxy, mercapto, optionally substituted amino, carboxy, cyano, or nitro; R B and R C are each independently hydrogen atom, alkyl, or alkyloxy; provided that in the case of both of R B and R C are hydrogen atom, R 1 is hydrogen atom or alkyl, R 2 is optionally substituted amino, alkyloxy, hydroxy, cyano, or nitro; and R 3 and R 4 are each independently hydrogen atom, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted aralkyl, optionally substituted non-aromatic heterocyclic group, acyl, optionally substituted amino, alkyloxy, hydroxy, cyano, or nitro; or R 3 and R 4 each taken together with the adjacent nitrogen atom form the same or different 3- to 7- membered ring optionally containing O, N, or S; X is -N(R 7 )-, -NH-NH-, -O-, or -S- wherein R 7 is hydrogen atom or optionally substituted alkyl; Y is optionally substituted 5- membered non-aromatic heterocycle-diyl or optionally substituted 5- membered heteroaryl-diyl; Z is optionally substituted aryl or optionally substituted heteroaryl; its optical active compound, its prodrug thereof, or their pharmaceutically acceptable salt, or their solvate. In more detail, the present invention relates to II)-XVI): II) a compound described in I), represented by the formula (II) : wherein R 8 , R 9 , R 10 , and R 11 are each independently hydrogen atom, optionally substituted alkyl, alkenyl, alkynyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted aralkyl, a non-aromatic heterocyclic group, acyl, optionally substituted amino, alkyloxy, hydroxy, cyano, or nitro; R B and R C are each independently hydrogen atom, alkyl, or alkyloxy; provided that in the case of both of R B and R C are hydrogen atom, R 8 is hydrogen atom or alkyl, R 9 is substituted amino, alkyloxy, hydroxy, cyano, or nitro; and R 10 and R 11 are each independently hydrogen atom, optionally substituted alkyl, alkenyl, alkynyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted aralkyl, non-aromatic heterocyclic group, acyl, optionally substituted amino, alkyloxy, hydroxy, cyano, or nitro; W is -O-, -S-, or -N(R A )- wherein R A is hydrogen atom or optionally substituted alkyl; R 5 , R 6 , X, and Z are as defined above mentioned I); its optical active compound, its prodrug thereof, or their pharmaceutically acceptable salt, or their solvate. III) a compound described in I), represented by the formula (III) : wherein R 5 , R 6 , and Z are as defined above mentioned I); R 8 , R 9 , R 10 , R 11 , R B and R C are as defined above mentioned II); its optical active compound, its prodrug thereof, or their pharmaceutically acceptable salt, or their solvate. IV) a compound described in I), represented by the formula (IV) : wherein R 8 , R 9 , R 10 and R 11 are as defined above mentioned II); R 12 is hydrogen atom or alkyl; R D and R E are each independently hydrogen atom or alkyl; provided that in the case of both of R D and R E are hydrogen atom, R 8 is hydrogen atom or alkyl, R 9 is optionally substituted amino, alkyloxy, hydroxy, cyano, or nitro; and R 10 and R 11 are each independently hydrogen atom, optionally substituted alkyl, alkenyl, alkynyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted aralkyl, non-aromatic heterocyclic group, acyl, optionally substituted amino, alkyloxy, hydroxy, cyano, or nitro; V is optionally substituted aryl; its optical active compound, its prodrug thereof, or their pharmaceutically acceptable salt, or their solvate. V) a compound represented by the formula (V) : wherein R 5 and R 6 are each independently hydrogen atom, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted alkyloxy, alkylthio, optionally substituted alkyloxycarbonyl, optionally substituted aryl, optionally substituted heteroaryl, halogen atoms, hydroxy, mercapto, optionally substituted amino, carboxy, cyano, or nitro; R F and R G are each independently hydrogen atom, alkyl, or alkyloxy; X is -N(R 7 )-, -NH-NH-, -O-, or -S- wherein R 7 is hydrogen atom or optionally substituted alkyl; Y is optionally substituted 5- membered non-aromatic heterocycle-diyl or optionally substituted 5- membered heteroaryl-diyl; Z is optionally substituted aryl or optionally substituted heteroaryl; Q 1 is -NR 1 R 2 , -OR 1 , or -SR 1 , T 1 is -OR 3 or -SR 3 wherein R 1 , R 2 and R 3 are each independently hydrogen atom, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted aralkyl, optionally substituted non-aromatic heterocyclic group, acyl, optionally substituted amino, alkyloxy, hydroxy, cyano, or nitro; or R 1 and R 3 , and R 2 and R 3 each taken together with the adjacent heteroatom form 5- to 7- membered ring; its regioisomer, its optical active compound, its prodrug thereof, or their pharmaceutically acceptable salt, or their solvate. VI) a compound described in V), represented by the formula (VI) wherein Q 2 is -NR 8 R 9 , -OR 8 , or -SR 8 , T 2 is -OR 10 or -SR 10 wherein R 8 , R 9 and R 10 are each independently hydrogen atom, optionally substituted alkyl, alkenyl, alkynyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted aralkyl, optionally substituted non-aromatic heterocyclic group, acyl, optionally substituted amino, alkyloxy, hydroxy, cyano, or nitro; W is -O-, -S-, or -N(R A )- wherein R A is hydrogen atom or optionally substituted alkyl; R 5 , R 6 , R F , R G , X, and Z are as defined above mentioned V); its regioisomer, its optical active compound, its prodrug thereof, or their pharmaceutically acceptable salt, or their solvate. In the case of R 8 and R 10 are bonded directly with O or S, R 8 and R 10 peferably are each independently hydrogen atom, optionally substituted alkyl, alkenyl, alkynyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted aralkyl, non-aromatic heterocyclic group, or acyl; VII) a compound described in V), represented by the formula (VII) : wherein R 5 , R 6 , R F , R G , and Z are as defined above mentioned V); Q 2 and T 2 are as defined above mentioned VI) its regioisomer, its optical active compound, its prodrug thereof, or their pharmaceutically acceptable salt, or their solvate. VIII) a compound described in V), represented by the formula (VIII) : wherein R 12 is hydrogen or alkyl; R H and R J are each independently hydrogen atom or alkyl; V is optically substituted aryl; the other symbols are as defined above mentioned VI); its regioisomer, its optical active compound, its prodrug thereof, or their pharmaceutically acceptable salt, or their solvate. IX) a compound, its regioisomer, its optical active compound, its prodrug thereof, or their pharmaceutically acceptable salt, or their solvate as described in any one of the above I) to V), wherein R 1 , R 2 , R 3 , and R 4 are each independently hydrogen atom, optionally substituted alkyl, alkenyl, alkynyl, or acyl, X) a compound, its regioisomer, its optical active compound, its prodrug thereof, or their pharmaceutically acceptable salt, or their solvate as described in any one of the above VI) to VIII), wherein R 8 , R 9 , R 10 , and R 11 are each independently hydrogen atom, optionally substituted alkyl, alkenyl, alkynyl, or acyl, XI) a pharmaceutical composition which contains as active ingredient a compound as described in any one of I) to X), XII) a pharmaceutical composition for use as an antitumor agent which contains as active ingredient a compound as described in any one of I) to X), XIII) a pharmaceutical composition for use as a cytostatic agent which contains as described in any one of I) to X), XIV) a pharmaceutical composition for use as an inhibitor against a signal derived from Ras oncogene products which contains as active ingredient a compound as described in any one of I) to X), XV) use of a compound of any one of I) to X) for the preparation of a pharmaceutical composition for treating cancer, and XVI) a method of treating a mammal, including a human, to alleviate a pathological effect of cancer, which comprises administration to the mammal of a compound as described in any one of I) to X). The term "alkyl" employed alone or in combination with other terms in the present specification includes a straight or branched chain monovalent hydrocarbon group having 1 to 8 carbon atoms. Examples of the alkyl include methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, isopentyl, neopentyl, n-hexyl, isohexyl, n-heptyl, n-octyl and the like. Preferably, C1 to C6 alkyl is exemplified. More preferably, C1 to C3 alkyl is exemplified. The term "alkenyl" employed alone or in combination with other terms in the present specification includes a straight or branched chain monovalent hydrocarbon group having 2 to 8 carbon atoms and one or more double bonds. An example of the alkenyl includes vinyl, allyl, propenyl, crotonyl, prenyl, a variety of butenyl isomers and the like. Preferably, C2 to C6 alkenyl is exemplified. More preferably, C2 to C3 alkenyl is exemplified. The term "alkynyl" employed alone or in combination with other terms in the present specification includes a straight or branched chain monovalent hydrocarbon group having 2 to 8 carbon atoms and one or more triple bonds. The alkynyl may contain (a) double bond(s). An example of the alkenyl includes ethynyl, propynyl, 6-heptynyl, 7-octynyl, and the like. Preferably, C2 to C6 alkynyl is exemplified. More preferably, C2 to C3 alkynyl is exemplified. The term "aryl" employed alone or in combination with other terms in the present specification includes a monocyclic or condensed cyclic aromatic hydrocarbon. An example of the aryl includes phenyl, 1-naphthyl, 2-naphthyl, anthryl and the like. Preferably, phenyl, 1-naphthyl, and 2-naphthyl are exemplified. More preferably, phenyl is exemplified. The term "aralkyl" in the present specification includes a group wherein the above-mentioned "alkyl" is substituted with the above-mentioned "aryl". An example of aralkyl includes benzyl, phenethyl (e.g., 2-phenylethyl), phenylpropyl (e.g., 3-phenylpropyl), naphthylmethyl (e.g., 1-naphthylmethyl and 2-naphthylmethyl), anthrylmethyl (e.g., 9-anthrylmethyl) and the like. Preferably, benzyl and phenylethyl are exemplified. The term "heteroaryl" employed alone or in combination with other terms in the present specification includes a 5- to 6- membered aromatic cyclic group which contains one or more hetero atoms selected from the group consisting of oxygen, sulfur, and nitrogen atoms in the ring and may be fused with the above mentioned "aryl", the later mentioned "carbocyclic group", and "non-aromatic heterocyclic group", or "heteroaryl". Heteroaryl is bonded at any possible position when the heteroaryl is a condensed ring. Examples of the heteroaryl are pyrrolyl (e.g., 1-pyrrolyl), indolyl (e.g., 3-indolyl), carbazolyl (e.g., 3-carbazolyl), imidazolyl (e.g., 4- imidazolyl), pyrazolyl (e.g., 3-pyrazolyl and 5-pyrazolyl), benzimidazolyl (e.g., 2-benzimidazolyl), indazolyl (e.g., 3-indazolyl), indolizinyl (e.g., 6-indolizinyl), pyridyl (e.g., 3-pyridyl and 4-pyridyl), quinolyl (e.g., 5-quinolyl), isoquinolyl (e.g., 3-isoquinolyl), acridinyl (e.g., 1-acridinyl), phenanthridinyl (e.g., 2-phenanthridinyl), pyridazinyl (e.g., 3-pyridazinyl), pyrimidinyl (e.g., 4-pyrimidinyl), pyrazinyl (e.g., 2-pyrazinyl), cinnolinyl (e.g., 3-cinnolinyl), phthalazinyl (e.g., 2-phthalazinyl), quinazolinyl (e.g., 2-quinazolinyl), isoxazolyl (e.g., 3-isoxazolyl), benzisoxazolyl (e.g., 3-benzisoxazolyl), oxazolyl (e.g., 2-oxazolyl), benzoxazolyl (e.g., 2-benzoxazolyl), benzoxadiazolyl (e.g., 4-benzoxadiazolyl), isothiazolyl (e.g., 3-isothiazolyl), benzisothiazolyl (e.g., 2-benzisothiazolyl), thiazolyl (e.g., 4-thiazolyl), benzothiazolyl (e.g., 2-benzothiazolyl), furyl (e.g., 2-furyl and 3-furyl), benzofuryl (e.g., 3-benzofuryl), thienyl (e.g., 2-thienyl and 3-thienyl), benzothienyl (e.g., 2-benzothienyl), tetrazolyl, oxadiazolyl (e.g., 1,3,4-oxadiazolyl and 1,2,4-oxadiazolyl), oxazolyl, thiadiazolyl (e.g., 1,3,4-thiadiazolyl and 1,2,4-thiadiazolyl), 4H-1,2,4-triazolyl, quinoxalinyl, 2-pyridon-3-yl, and the like. Preferably, pyridyl, pyrazinyl, furyl, thienyl and the like are exemplified. The term "5- membered heteroaryl-diyl" herein used includes a 5- membered divalent group derived from above-mentioned "heteroaryl". Examples of the 5-membered heteroaryl-diyl are furan-2,5-diyl, thiophene-2,5-diyl, pyrrole-2,5-diyl, pyrazole-3,5-diyl, 1,3,4-oxadiazole-2,5-diyl, 1,2,4-oxadiazole3,5-diyl, oxazole-3,5-diyl, isoxazole-3,5-diyl, 1,3,4-thiadiazole-3,5-diyl, 1,2,4-thiadiazole-3,5-diyl, 4H-1,2,4-triazole-3,5-diyl, and the like. The term "non-aromatic heterocyclic group" employed alone or in combination with other terms in the present specification includes a 5- to 7- membered non-aromatic heterocyclic group which contains one or more hetero atoms selected from the group consisting of oxygen, sulfur, and nitrogen atoms in the ring and a cyclic group wherein two or more of the above-mentioned heterocyclic groups are fused. Examples of the heterocyclic group are pyrrolidinyl (e.g., 1-pyrrolidinyl), pyrazolidinyl (e.g., 1-pyrazolidinyl), piperidinyl (e.g., piperidino and 2-piperidinyl), piperazinyl (e.g., 1-piperazinyl), morpholinyl (e.g., morpholino and 3-morpholinyl), and the like. The term "5- membered non-aromatic heterocycle-diyl" herein used includes a 5-membered divalent group derived from the above-mentioned "non-aromatic heterocyclic group". Examples of the 5- membered non-aromatic heterocycle-diyl are pyrrolidindiyl (e.g., pyrrolidine-2,5-diyl) and the like. The term "carbocyclic group" herein used includes a 3- to 7- membered non-aromatic carbocyclic group. Examples of the carbocyclic group are cycloalkyl (e.g., cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, and cycloheptyl), cycloalkenyl (e.g., cyclopentenyl and cyclohexenyl), and the like. In this specification, examples of the ring represented by "R 1 and R 2 , and R 3 and R 4 each taken together with the adjacent nitrogen atom form the same or different 3- to 7-membered non-aromatic heterocyclic ring optionally containing O, N, or S" are aziridine, pyrrolidine, piperidine, piperazine, morpholine, imidazolidine, pyrazolidine, pyrrole, pyrimidine, triazine, azepine, perhydroazepine, and the like. In this specification, examples of the ring represented by "R 2 and R 3 each taken together with the adjacent nitrogen atom form the same or different 3- to 7- membered non-aromatic heterocyclic ring optionally containing O, N, or S" are imidazolidine, hexahydropyridine, and perhydro-1,3-diazepine the like. In this specification, examples of the ring represented by "R 1 and R 3 , or R 2 and R 3 each taken together with heteroatom form 5- to 7- membered non-aromatic heterocyclic ring optionally containing O, N, or S " are thiazolidine, perhydro-1,3-thiadine, oxazolidine, perhydro-1,3-oxadine, 1,3-dithiolane, 1,3-dithiane, 1,3-oxathiolane, 1,3-oxathiane, perhydro-1,3-oxazepine, perhydro-1,3-thiazepine, and the like. The term "acyl" employed alone or in combination with other terms in the present specification includes alkylcarbonyl of which alkyl part is the above-mentioned "alkyl" and arylcarbonyl of which aryl part is the above-mentioned "aryl". Examples of the acyl are acetyl, propanoyl, benzoyl, and the like. The term "halogen" herein used means fluoro, chloro, bromo, and iodo. Examples of "alkyloxy" herein used are methyloxy, ethyloxy, n-propyloxy, isopropyloxy, n-butyloxy, isobutyloxy, sec-butyloxy, tert-butyloxy, and the like. Preferably, methyloxy, ethyloxy, n-propyloxy, and isopropyloxy are exemplified. Examples of "alkylthio" herein used are methylthio, ethylthio, n-propylthio, isopropylthio, n-butylthio, isobutylthio, sec-butylthio, tert-butylthio, and the like. Preferably, methylthio, ethylthio, n-propylthio, and isopropylthio are exemplified. Examples of "alkyloxycarbonyl" herein used are methyloxycarbonyl, ethyloxycarbonyl, n-propyloxycarbonyl, and the like. The term "optionally substituted amino" herein used means amino substituted with one or two of the above-mentioned "alkyl", the above-mentioned "aralkyl", the above-mentioned "acyl", optionally substituted arylsulfonyl (e.g., alkyloxyphenylsulfonyl), arylalkylene (e.g., benzylidene), alkylsulfonyl, carbamoyl and the like or non-substituted amino. Examples of the optionally substituted amino are amino, methylamino, ethylamino, dimethylamino, ethylmethylamino, diethylamino, benzylamino, benzoylamino, acetylamino, propionylamino, tert-butyloxycarbonylamino, benzylidenamino, methylsulfonylamino, 4-methoxyphenylsulfonylamino, and the like. Preferably, amino, methylamino, dimethylamino, diethylamino, acetylamino are exemplified. Substituents on the aromatic ring of "optionally substituted aralkyl" are, for example, hydroxy, alkyloxy (e.g., methyloxy and ethyloxy), mercapto, alkylthio (e.g., methylthio), cycloalkyl (e.g., cyclopropyl, cyclobutyl, and cyclopentyl), halogen (e.g., fluoro, chloro, bromo, and iodo), carboxy, alkyloxycarbonyl (e.g., methyloxycarbonyl and ethyloxycarbonyl), nitro, cyano, haloalkyl (e.g., trifluoromethyl), aryloxy (e.g., phenyloxy), optionally substituted amino (e.g., amino, methylamino, dimethylamino, diethylamino, and benzylidenamino), alkyl (e.g., methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, isopentyl, and neopentyl), alkenyl (e.g., vinyl and propenyl), alkynyl (e.g., ethynyl and phenylethynyl), formyl, lower alkanoyl (e.g., acetyl and propionyl), acyloxy (e.g., acetyloxy), acylamino, alkylsulfonyl (e.g., methylsulfonyl), and the like. These substituents may be substituted at one or more possible position(s). Substituents of "optionally substituted alkyl", "optionally substituted alkyloxy", and "optionally substituted alkyloxycarbonyl" are, for example, hydroxy, alkyloxy (e.g., methyloxy and ethyloxy), mercapto, alkylthio (e.g., methylthio), cycloalkyl (e.g., cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl), halogen (e.g., fluoro, chloro, bromo, and iodo), carboxy, alkyloxycarbonyl (e.g., methyloxycarbonyl and ethyloxycarbonyl), nitro, cyano, haloalkyl (e.g., trifluoromethyl), optionally substituted amino (e.g., amino, methylamino, dimethylamino, carbamoylamino, and tert-butyloxycarbonylamino), acyloxy (e.g., acetyloxy), optionally substituted aralkyloxy (e.g., benzyloxy and 4-methyloxybenzyloxy), and the like. These substituents may be substituted at one or more possible position(s). Substituents of "optionally substituted alkenyl" and "optionally substituted alkynyl" are, for example, hydroxy, alkyloxy (e.g., methyloxy and ethyloxy), mercapto, alkylthio (e.g., methylthio), cycloalkyl (e.g., cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl), halogen (e.g., fluoro, chloro, bromo, and iodo), carboxy, alkyloxycarbonyl (e.g., methyloxycarbonyl and ethyloxycarbonyl), nitro, cyano, haloalkyl (e.g., trifluoromethyl), optionally substituted amino (e.g., amino, methylamino, dimethylamino, carbamoylamino, and tert-butyloxycarbonylamino), acyloxy (e.g., acetyloxy), optionally substituted aralkyloxy (e.g., benzyloxy and 4-methyloxybenzyloxy), optionally substituted aryl (e.g., phenyl), and the like. These substituents may be substituted at one or more possible position(s). The preferable examples of "optionally substituted alkyl" are methyl, ethyl, n-propyl, isopropyl, n-butyl, trifluoromethyl, 2,2,2-trifluoroethyl, hydroxymethyl, cyclohexylmethyl, carboxyethyl, acetyloxyethyl, and benzyloxymethyl. More preferably, methyl, ethyl, n-propyl, isopropyl, n-butyl, trifluoromethyl, 2,2,2-trifluoroethyl are exemplified. Substituents of "optionally substituted aryl", "optionally substituted heteroaryl", "optionally substituted 5- membered heteroaryl-diyl", "optionally substituted 5- membered non-aromatic heterocycle-diyl", and "an optionally substituted non-aromatic heterocyclic group" are, for example, hydroxy, optionally substituted alkyloxy (e.g., methyloxy, ethyloxy, n-propyloxy, isopropyloxy, ethyloxycarbonylmethyloxy, carboxymethyloxy and 4-methoxybenzyloxy), mercapto, alkylthio (e.g., methylthio), cycloalkyl (e.g., cyclopropyl, cyclobutyl, cyclopentyl), halogen (e.g., fluoro, chloro, bromo, and iodo), carboxy, alkyloxycarbonyl (e.g., methyloxycarbonyl, ethyloxycarbonyl, and tert-butyloxycarbonyl), nitro, cyano, haloalkyl (e.g., trifluoromethyl), aryloxy (e.g., phenyloxy), optionally substituted amino (e.g., amino, methylamino, dimethylamino, ethylamino, diethylamino, acetylmethylamino, benzylidenamino, 4-methoxyphenylsulfonylamino, methylsulfonylamino, benzoylamino, acetylamino, propionylamino, and tert-butyloxycarbonylamino), optionally substituted sulfamoyl (e.g., sulfamoyl), optionally substituted alkyl (e.g., methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, isopentyl, neopentyl, t-butyloxycarbonylaminomethyl, and aminomethyl), alkenyl (e.g., vinyl, propenyl, and prenyl), optionally substituted alkynyl (e.g., ethynyl and phenylethynyl), alkenyloxy (e.g., propenyloxy and prenyloxy), formyl, acyl (e.g., acetyl, propionyl, and benzoyl), acyloxy (e.g., acetyloxy), optionally substituted carbamoyl (e.g., carbamoyl and N,N-dimethylcarbamoyl), alkylsulfonyl (e.g., methylsulfonyl), aryl (e.g., phenyl), aralkyl (e.g., benzyl), carbothioamide, optionally substituted heterocyclic group (e.g., dioxolanyl, 2-methyl-1,3-dioxolan-2-yl, pyrrolidinyl, and piperidino), optionally substituted heteroaryl (e.g., 2-pyridyl, 3-pyridyl, 4-pyridyl, pyridine N-oxide-4-yl, 1-methyl-2-pyridon-4-yl, 1-pyrrolyl, 2-pyrrolyl, and 3-pyrrolyl), and the like. These substituents may be substituted at one or more possible position(s). Preferably, optionally substituted amino, halogen, nitro, alkyl, and alkyloxy are exemplified. Examples of "optionally substituted aryl" are phenyl, 2-aminophenyl, 3-aminophenyl, 4-aminophenyl, 2-acetylaminophenyl, 4-acetylaminophenyl, 2-benzoylaminophenyl, 4-benzoylaminophenyl, 2-methylsulfonylaminophenyl, 2-propionylaminophenyl, 2-methylaminophenyl, 4-methylaminophenyl, 2-dimethylaminophenyl, 4-dimethylaminophenyl, 2-ethylaminophenyl, 4-ethylaminophenyl, 4-diethylaminophenyl, 2- (4-methoxyphenylsulfonylamino)phenyl, 2-hydroxyphenyl, 4-hydroxyphenyl, 2-ethyloxycarbonylmethyloxyphenyl, 2-carboxymethyloxyphenyl, 2-chlorophenyl, 4-chlorophenyl, 4-bromophenyl, 4-iodophenyl, 4-trifluoromethylphenyl, 2-methylphenyl, 4-methylphenyl, 4-methyloxyphenyl, 4-ethyloxyphenyl, 4-n-propyloxyphenyl, 4-isopropyloxyphenyl, 4-tert-butyloxycarbonylphenyl, 4-prenyloxyphenyl, 2-nitrophenyl, 4-nitrophenyl, 4-(4-methoxybenzyloxy)phenyl, 4-methyloxycarbonylphenyl, 4-sulfamoylphenyl, 4-(N,N-dimethylcarbamoyl)phenyl, 4-carboxyphenyl, 4-biphenylyl, 4-benzoylphenyl, 4-pyrrolidinophenyl, 4-piperidinophenyl, 3-aminonaphthalen-2-yl, 2-amino-5-chlorophenyl, 2-amino-3-chlorophenyl, 2-amino-4-chlorophenyl, 2-amino-6-chlorophenyl, 4-amino-2-chlorophenyl, 2-amino-4-fluorophenyl, 2-amino-5-fluorophenyl, 2-amino-6-fluorophenyl, 4-amino-2-fluorophenyl, 2-amino-4,5-difluorophenyl, 2-amino-3-methylphenyl, 2-amino-4-methylphenyl, 2-amino-5-methylphenyl, 2-amino-6-methylphenyl, 4-amino-3-methylphenyl, 4-amino-3-methyloxyphenyl, 2-amino-4-nitrophenyl, 4-amino-3-hydroxyphenyl, 2-amino-4-carboxyphenyl, 2-amino-4-methyloxycarbonylphenyl, 4-amino-2-hydroxyphenyl, 4-amino-3-(4-methoxypbenzyloxy)phenyl, 2,4-diaminophenyl, 3,4-diaminophenyl, 2-acetylmethylaminophenyl, 2-acetylamino-4-fluorophenyl, 2-acetylamino-4-chlorophenyl, 2,3-dichlorophenyl, 2,4-dichlorophenyl, 4-amino-2-methylphenyl, 2-fluoro-4-nitrophenyl, 4-amino-2-methyloxyphenyl, 2-methyloxy-4-nitrophenyl, 4-fluoro-2-nitrophenyl, 4-amino-2-trifluoromethylphenyl, 4-amino-2-ethyloxyphenyl, 4-amino-2-trifluoromethyloxyphenyl, 2-chloro-4-nitrophenyl, 2-methyl-4-nitrophenyl, 4-nitro-2-trifluoromethyloxyphenyl, 4-nitro-2-trifluoromethylphenyl, 2-ethyloxy-4-nitrophenyl, and the like. Examples of "optionally substituted heteroaryl" are pyridin-3-yl, 2-aminopyridin-3-yl, 2-aminopyridin-5-yl, 3-aminopyrazin-2-yl, 3-aminopyrazol-4-yl, 4-amino-2-methylpyrimidin-5-yl, 2-aminothiophen-3-yl, 3-methylthiophen-2-yl, 5-methylthiophen-2-nyl, furan-2-yl, furan-3-yl, 2-methylfuran-3-yl, 2,5-dimethylfuran-3-yl, 5-bromofuran-2-yl, 2-nitrofuran-4-yl, 1-methyl-4-nitropyrazol-3-yl, 1-methyl-4-nitropyrazol-5-yl, 5-nitropyrazol-3-yl, 4-nitropyrazol-3-yl, 2-(3-pyridyl)thiazol-4-yl, 2-(4-pyridyl)thiazol-4-yl, 6-(1-pyrrolyl)pyridin-3-yl, N-methyl-2-pyridon-3-yl, and the like. Examples of "optionally substituted 5- membered heteroaryl-diyl" are furan-2,5-diyl, thiophene-2,5-diyl, pyrrole-2,5-diyl, pyrazole-3,5-diyl, 1,3,4-oxadiazole-2,5-diyl, 1,2,4-oxadiazole-3,5-diyl, oxazole-2,5-diyl, isooxazole-3,5-diyl, 1,3,4-thiadiazole-2,5-diyl, 1,2,4-thiadiazole-3,5-diyl, 4H-1,2,4-triazole-3,5-diyl, 1-methylpyrazole-3,5-diyl, and the like. Preferable examples of R 1 to R 6 , R B , R C , X, Y, and Z of the compound represented by the formula (I) are shown below as groups (a) to (t). R 1 and R 2 are (a) one is hydrogen atom, the other is optionally substituted amino, alkyloxy, hydroxy, cyano, or nitro. R 3 and R 4 are (b) each independently hydrogen atom, optionally substituted alkyl, alkenyl, alkynyl, optionally substituted amino, alkyloxy, hydroxy, cyano, or nitro; (c) each independently hydrogen atom, alkyl optionally substituted with halogen atom, alkenyl, or alkynyl, optionally substituted amino, alkyloxy, hydroxy, cyano, or nitro; and (d) one is hydrogen atom and the other is alkyl optionally substituted with halogen, alkenyl, or alkynyl, optionally substituted amino, alkyloxy, hydroxy; cyano, or nitro. R 5 is (e) hydrogen atom, alkyloxy, alkylthio, or optionally substituted alkyl; (f) hydrogen atom or alkyl; and (g) hydrogen atom or C1 to C2 alkyl. R 6 is (h) hydrogen atom or alkyl; and (i) hydrogen atom. X is (j) -O- or -S-; and (k) -S-. Y is (l) 5- membered heteroaryl-diyl; (m) 1,3,4-oxadiazole-2,5-diyl, 1,2,4-oxadiazole-3,5-diyl, 1,3,4-thiadiazole-2,5-diyl, or 1,2,4-thiadiazole-3,5-diyl; and (n) 1,3,4-oxadiazole-2,5-diyl. Z is (o) optionally substituted aryl or optionally substituted heteroaryl; (p) optionally substituted phenyl or optionally substituted monocyclic heteroaryl; and (q) phenyl, pyridyl, thienyl, or furyl, which are substituted with 1 to 3 substituents selected from the group consisting of optionally substituted amino, halogen, alkyl, alkyloxy, acyl, phenyl, alkyloxycarbonyl, hydroxy, nitro, or haloalkyl. A preferable example of R B and R C is (r) (R B , R C ) is (alkyl, hydrogen atom) or (hydrogen atom, hydrogen atom); and (s) (R B , R C ) is (hydrogen atom, hydrogen atom). A preferred group of compounds represented by the formula (I) is shown below. [(R 1 , R 2 ), (R 3 , R 4 ), R 5 , R 6 , X, Y, (R B , R C )]=[a, b, e, h, j, l, r], [a, b, e, h, j, l, s], [a, b, e, h, j, m, r], [a, b, e, h, j, m, s], [a, b, e, h, j, n, r], [a, b, e, h, j, n, s], [a, b, e, h, k, l, r], [a, b, e, h, k, l, s], [a, b, e, h, k, m, r], [a, b, e, h, k, m, s], [a, b, e, h, k, n, r], [a, b, e, h, k, n, s], [a, b, e, i, j, l, r], [a, b, e, i, j, l, s], [a, b, e, i, j, m, r], [a, b, e, i, j, m, s], [a, b, e, i, j, n, r], [a, b, e, i, j, n, s], [a, b, e, i, k, l, r], [a, b, e, i, k, l, s], [a, b, e, i, k, m, r], [a, b, e, i, k, m, s], [a, b, e, i, k, n, r], [a, b, e, i, k, n, s], [a, b, f, h, j, l, r], [a, b, f, h, j, l, s], [a, b, f, h, j, m, r], [a, b, f, h, j, m, s], [a, b, f, h, j, n, r], [a, b, f, h, j, n, s], [a, b, f, h, k, l, r], [a, b, f, h, k, l, s], [a, b, f, h, k, m, r], [a, b, f, h, k, m, s], [a, b, f, h, k, n, r], [a, b, f, h, k, n, s], [a, b, f, i, j, l, r], [a, b, f, i, j, l, s], [a, b, f, i, j, m, r], [a, b, f, i, j, m, s], [a, b, f, i, j, n, r], [a, b, f, i, j, n, s], [a, b, f, i, k, l, r], [a, b, f, i, k, l, s], [a, b, f, i, k, m, r], [a, b, f, i, k, m, s], [a, b, f, i, k, n, r], [a, b, f, i, k, n, s], [a, b, g, h, j, l, r], [a, b, g, h, j, l, s], [a, b, g, h, j, m, r], [a, b, g, h, j, m, s], [a, b, g, h, j, n, r], [a, b, g, h, j, n, s], [a, b, g, h, k, l, r], [a, b, g, h, k, l, s], [a, b, g, h, k, m, r], [a, b, g, h, k, m, s], [a, b, g, h, k, n, r], [a, b, g, h, k, n, s], [a, b, g, i, j, l, r], [a, b, g, i, j, l, s], [a, b, g, i, j, m, r], [a, b, g, i, j, m, s], [a, b, g, i, j, n, r], [a, b, g, i, j, n, s], [a, b, g, i, k, l, r], [a, b, g, i, k,l, s], [a, b, g, i, k, m, r], [a, b, g, i, k, m, s], [a, b, g, i, k, n, r], [a, b, g, i, k, n, s], [a, c, e, h, j, l, r], [a, c, e, h,j, l, s], [a, c, e, h, j, m, r], [a, c, e, h, j, m, s], [a, c, e, h, j, n, r], [a, c, e, h, j, n, s], [a, c, e, h, k, l, r], [a, c, e, h, k, l, s], [a, c, e, h, k, m, r], [a, c, e, h, k, m, s], [a, c, e, h, k, n, r], [a, c, e, h, k, n, s], [a, c, e, i, j, l, r], [a, c, e, i, j, 1, s], [a, c, e, i, j, m, r], [a, c, e, i, j, m, s], [a, c, e, i, j, n, r], [a, c, e, i, j, n, s], [a, c, e, i, k,l, r], [a, c, e, i, k, l, s], [a, c, e, i, k, m, r], [a, c, e, i, k, m, s], [a, c, e, i, k, n, r], [a, c, e, i, k, n, s], [a, c, f, h, j, l, r], [a, c, f, h, j, l, s], [a, c, f, h, j, m, r], [a, c, f, h, j, m, s], [a, c, f, h, j, n, r], [a, c, f, h, j, n, s], [a, c, f, h, k, l, r], [a, c, f, h, k, I, s], [a, c, f, h, k, m, r], [a, c, f, h, k, m, s], [a, c, f, h, k, n, r], [a, c, f, h, k, n, s], [a, c, f, i, j, l, r], [a, c, f, i, j, l, s], [a, c, f, i, j, m, r], [a, c, f, i, j, m, s], [a, c, f, i, j, n, r], [a, c, f, i, j, n, s], [a, c, f, i, k, l, r], [a, c, f, i, k, l, s], [a, c, f, i, k, m, r], [a, c, f, i, k, m, s], [a, c, f, i, k, n, r], [a, c, f, i, k, n, s], [a, c, g, h, j, l, r], [a, c, g, h, j, l, s], [a, c, g, h, j, m, r], [a, c, g, h, j, m, s], [a, c, g, h, j, n, r], [a, c, g, h, j, n, s], [a, c, g, h, k, l, r], [a, c, g, h, k, l, s], [a, c, g, h, k, m, r], [a, c, g, h, k, m, s], [a, c, g, h, k, n, r], [a, c, g, h, k, n, s], [a, c, g, i, j, l, r], [a, c, g, i, j, l, s], [a, c, g, i, j, m, r], [a, c, g, i, j, m, s], [a, c, g, i, j, n, r], [a, c, g, i, j, n, s], [a, c, g, i, k, l, r], [a, c, g, i, k, l, s], [a, c, g, i, k, m, r], [a, c, g, i, k, m, s], [a, c, g, i, k, n, r], [a, c, g, i, k, n, s], [a, d, e, h, j, l, r], [a, d, e, h, j, l, s], [a, d, e, h, j, m, r], [a, d, e, h, j, m, s], [a, d, e, h, j, n, r], [a, d, e, h, j, n, s], [a, d, e, h, k, l, r], [a, d, e, h, k, I, s], [a, d, e, h, k, m, r], [a, d, e, h, k, m, s], [a, d, e, h, k, n, r], [a, d, e, h, k, n, s], [a, d, e, i, j, l, r], [a, d, e, i, j, l, s], [a, d, e, i, j, m, r], [a, d, e, i, j, m, s], [a, d, e, i, j, n, r], [a, d, e, i, j, n, s], [a, d, e, i, k, l, r], [a, d, e, i, k, l, s], [a, d, e, i, k, m, r], [a, d, e, i, k, m, s], [a, d, e, i, k, n, r], [a, d, e, i, k, n, s], [a, d, f, h, j, l, r], [a, d, f, h, j, l, s], [a, d, f, h, j, m, r], [a, d, f, h, j, m, s], [a, d, f, h, j, n, r], [a, d, f, h, j, n, s], [a, d, f, h, k, I, r], [a, d, f, h, k, l, s], [a, d, f, h, k, m, r], [a, d, f, h, k, m, s], [a, d, f, h, k, n, r], [a, d, f, h, k, n, s], [a, d, f, i, j, l, r], [a, d, f, i, j, l, s], [a, d, f, i, j, m, r], [a, d, f, i, j, m, s], [a, d, f, i, j, n, r], [a, d, f, i, j, n, s], [a, d, f, i, k, l, r], [a, d, f, i, k, l, s], [a, d, f, i, k, m, r], [a, d, f, i, k, m, s], [a, d, f, i, k, n, r], [a, d, f, i, k, n, s], [a, d, g, h,j, l, r], [a, d, g, h,j, l, s], [a, d, g, h,j, m, r], [a, d, g, h,j, m, s], [a, d, g, h,j, n, r], [a, d, g, h,j, n, s], [a, d, g, h, k, l, r], [a, d, g, h, k, l, s], [a, d, g, h, k, m, r], [a, d, g, h, k, m, s], [a, d, g, h, k, n, r], [a, d, g, h, k, n, s], [a, d, g, i,j, l, r], [a, d, g, i, j, l, s], [a, d, g, i, j, m, r], [a, d, g, i, j, m, s], [a, d, g, i, j, n, r], [a, d, g, i, j, n, s], [a, d, g, i, k, l, r], [a, d, g, i, k, l, s], [a, d, g, i, k, m, r], [a, d, g, i, k, m, s], [a, d, g, i, k, n, r], [a, d, g, i, k, n, s] Preferred embodiments of this invention are compounds wherein Z is any one of (o) to (q) and [(R 1 , R 2 ), (R 3 , R 4 ), R 5 , R 6 , X, Y, (R B , R C )] is any one of the above combinations. Preferable examples of R 5 , R 6 , R F , R G , Q 1 , T 1 , X, Y, and Z of the compound represented by the formula (V) are shown below as groups (a) to (r). R 5 is (a) hydrogen atom, alkyloxy, alkylthio, or optionally substituted alkyl; (b) hydrogen atom or alkyl; and (c) hydrogen atom or C1 to C2 alkyl. R 3 is (d) hydrogen atom or alkyl; and (e) hydrogen atom. A preferable example of R F and R G is (f) (R B , R C ) is (hydrogen atom, hydrogen atom), (hydrogen atom, alkyl), (alkyl, alkyl), or (hydrogen atom, alkyloxy); and (g) is (hydrogen atom, hydrogen atom), (hydrogen atom, alkyl), or (alkyl, alkyl). Q 1 and T 1 are (h) Q 1 is -NR 1 R 2 or -SR 1 wherein R 1 and R 2 are each independently hydrogen atom, optionally substituted alkyl, alkenyl, or alkynyl, T 1 is -SR 3 wherein R 3 is hydrogen atom, optionally substituted alkyl, alkenyl, or alkynyl; (i) Q 1 is -NR 1 R 2 or -SR 1 wherein R 1 and R 2 are each independently hydrogen atom, alkyl optionally substituted with halogen, alkenyl, or alkynyl, T 1 is -SR 3 wherein R 3 is hydrogen atom, alkyl optionally substituted with halogen, alkenyl, or alkynyl; (j) Q 1 is -NR 1 R 2 or -SR 1 wherein R 1 and R 2 are one is hydrogen atom and the other is C1 to C3 alkyl optionally substituted with halogen, T 1 is -SR 3 wherein R 3 is hydrogen atom or alkyl optionally substituted with halogen. X is (k) -O- or -S-; and (l) -S-. Y is (m) 5- membered heteroaryl-diyl; (n) 1,3,4-oxadiazole-2,5-diyl, 1,2,4-oxadiazole-3,5-diyl, 1,3,4-thiadiazole-2,5-diyl, or 1,2,4-thiadiazole-3,5-diyl; and (o) 1,3,4-oxadiazole-2,5-diyl. Z is (p) optionally substituted aryl or optionally substituted heteroaryl; (q) optionally substituted phenyl or optionally substituted monocyclic heteroaryl; and (r) phenyl, pyridyl, thienyl, or furyl, which are substituted with 1 to 3 substituents selected from the group consisting of optionally substituted amino, halogen, alkyl, alkyloxy, acyl, phenyl, alkyloxycarbonyl, hydroxy, nitro, or haloalkyl. A preferred group of compounds represented by the formula (V) is shown below. [R 5 , R 6 , (R F , R G ), (Q 1 , T 1 ), X, Y]=[a, d, f, h, k, m], [a, d, f, h, k, n], [a, d, f, h, k, o], [a, d, f, h, l, m], [a, d, f, h, l, n], [a, d, f, h, l, o], [a, d, f, i, k, m], [a, d, f, i, k, n], [a, d, f, i, k, o], [a, d, f, i, l, m], [a, d, f, i, l, n], [a, d, f, i, l, o], [a, d, f, j, k, m], [a, d, f, j, k, n], [a, d, f, j, k, o], [a, d, f, j, l, m], [a, d, f, j, l, n], [a, d, f,j, l, o], [a, d, g, h, k, m], [a, d, g, h, k, n], [a, d, g, h, k, o], [a, d, g, h, l, m], [a, d, g, h, l, n], [a, d, g, h, l, o], [a, d, g, i, k, m], [a, d, g, i, k, n], [a, d, g, i, k, o], [a, d, g, i, l, m], [a, d, g, i, l, n], [a, d, g, i, l, o], [a, d, g, j, k, m], [a, d, g, j, k, n], [a, d, g, j, k, o], [a, d, g, j, l, m], [a, d, g, j, l, n], [a, d, g, j, l, o], [a, e, f, h, k, m], [a, e, f, h, k, n], [a, e, f, h, k, o], [a, e, f, h, I, m], [a, e, f, h, l, n], [a, e, f, h, l, o], [a, e, f, i, k, m], [a, e, f, i, k, n], [a, e, f, i, k, o], [a, e, f, i, l, m], [a, e, f, i, l, n], [a, e, f, i, l, o], [a, e, f, j, k, m], [a, e, f, j, k, n], [a, e, f, j, k, o], [a, e, f, j, I, m], [a, e, f, j, l, n], [a, e, f, j, l, o], [a, e, g, h, k, m], [a, e, g, h, k, n], [a, e, g, h, k, o], [a, e, g, h, I, m], [a, e, g, h, I, n], [a, e, g, h, l, o], [a, e, g, i, k, m], [a, e, g, i, k, n], [a, e, g, i, k, o], [a, e, g, i, l, m], [a, e, g, i, l, n], [a, e, g, i, l, o], [a, e, g, j, k, m], [a, e, g, j, k, n], [a, e, g, j, k, o], [a, e, g, j, l, m], [a, e, g, j, l, n], [a, e, g, j, l, o], [b, d, f, h, k, m], [b, d, f, h, k, n], [b, d, f, h, k, o], [b, d, f, h, l, m], [b, d, f, h, l, n], [b, d, f, h, l, o], [b, d, f, i, k, m], [b, d, f, i, k, n], [b, d, f, i, k, o], [b, d, f, i, l, m], [b, d, f, i, l, n], [b, d, f, i, l, o], [b, d, f, j, k, m], [b, d, f, j, k, n], [b, d, f, j, k, o], [b, d, f, j, l, m], [b, d, f, j, l, n], [b, d, f, j, I, o], [b, d, g, h, k, m], [b, d, g, h, k, n], [b, d, g, h, k, o], [b, d, g, h, l, m], [b, d, g, h, l, n], [b, d, g, h, l, o], [b, d, g, i, k, m], [b, d, g, i, k, n], [b, d, g, i, k, o], [b, d, g, i, l, m], [b, d, g, i, l, n], [b, d, g, i, l, o], [b, d, g, j, k, m], [b, d, g, j, k, n], [b, d, g, j, k, o], [b, d, g, j, l, m], [b, d, g, j, l, n], [b, d, g, j, l, o], [b, e, f, h, k, m], [b, e, f, h, k, n], [b, e, f, h, k, o], [b, e, f, h, l, m], [b, e, f, h, l, n], [b, e, f, h, l, o], [b, e, f, i, k, m], [b, e, f, i, k, n], [b, e, f, i, k, o], [b, e, f, i, ], m], [b, e, f, i, l, n], [b, e, f, i, l, o], [b, e, f, j, k, m], [b, e, f, j, k, n], [b, e, f, j, k, o], [b, e, f, j, l, m], [b, e, f, j, l, n], [b, e, f, j, l, o], [b, e, g, h, k, m], [b, e, g, h, k, n], [b, e, g, h, k, o], [b, e, g, h, l, m], [b, e, g, h, l, n], [b, e, g, h, l, o], [b, e, g, i, k, m], [b, e, g, i, k, n], [b, e, g, i, k, o], [b, e, g, i, l, m], [b, e, g, i, l, n], [b, e, g, i, l, o], [b, e, g, j, k, m], [b, e, g, j, k, n], [b, e, g, j, k, o], [b, e, g, j, l, m], [b, e, g, j, l, n], [b, e, g, j, I, o], [c, d, f, h, k, m], [c, d, f, h, k, n], [c, d, f, h, k, o], [c, d, f, h, l, m], [c, d, f, h, l, n], [c, d, f, h, l, o], [c, d, f, i, k, m], [c, d, f, i, k, n], [c, d, f, i, k, o], [c, d, f, i, I, m], [c, d, f, i, l, n], [c, d, f, i, l, o], [c, d, f, j, k, m], [c, d, f, j, k, n], [c, d, f, j, k, o], [c, d, f, j, l, m], [c, d, f, j, l, n], [c, d, f, j, l, o], [c, d, g, h, k, m], [c, d, g, h, k, n], [c, d, g, h, k, o], [c, d, g, h, l, m], [c, d, g, h, l, n], [c, d, g, h, l, o], [c, d, g, i, k, m], [c, d, g, i, k, n], [c, d, g, i, k, o], [c, d, g, i, l, m], [c, d, g, i, l, n], [c, d, g, i, l, o], [c, d, g, j, k, m], [c, d, g, j, k, n], [c, d, g, j, k, o], [c, d, g, j, l, m], [c, d, g, j, l, n], [c, d, g, j, l, o], [c, e, f, h, k, m], [c, e, f, h, k, n], [c, e, f, h, k, o], [c, e, f, h, I, m], [c, e, f, h, l, n], [c, e, f, h, I, o], [c, e, f, i, k, m], [c, e, f, i, k, n], [c, e, f, i, k, o], [c, e, f, i, I, m], [c, e, f, i, l, n], [c, e, f, i, I, o], [c, e, f, j, k, m], [c, e, f, j, k, n], [c, e, f, j, k, o], [c, e, f, j, l, m], [c, e, f, j, I, n], [c, e, f, j, l, o], [c, e, g, h, k, m], [c, e, g, h, k, n], [c, e, g, h, k, o], [c, e, g, h, l, m], [c, e, g, h, I, n], [c, e, g, h, l, o], [c, e, g, i, k, m], [c, e, g, i, k, n], [c, e, g, i, k, o], [c, e, g, i, l, m], [c, e, g, i, l, n], [c, e, g, i, I, o], [c, e, g, j, k, m], [c, e, g, j, k, n], [c, e, g, j, k, o], [c, e, g, j, l, m], [c, e, g, j, l, n], [c, e, g, j, l, o] Preferred embodiments of this invention are compounds wherein Z is any one of (p) to (r) and [R 5 , R 6 , (R F , R G ), (Q 1 , T 1 ), X, Y] is any one of the above combinations. In this specification, the compounds represented by the formula (I) may be represented by the below formula. The compounds represented by the formula (II), (III), and (IV) are as well as the above. In this specification, a compound of formula (I) wherein R 1 is hydrogen atom may be represented as an isomer of the formula (IX). wherein R 2 , R 3 , R 4 , R 5 , R 6 , R B , R C , X, Y, and Z are as defined above; R 1 is hydrogen atom. The compounds represented by the formula (II), (III), and (IV) are as well as the above. In this specification, a compound of formula (V) wherein T 1 is -SR 3 wherein R 3 is hydrogen atom may be represented as an isomer of the formula (X). The compounds wherein T 1 is -OR 3 wherein R 3 is hydrogen atom are as well as the above. wherein R 5 , R 6 , R F , R G , Q 1 , X, Y, and Z are as defined above; R 3 is hydrogen atom. The compounds represented by the formulae (VI), (VII), and (VIII) are as well as the above. In this specification, according to alkylation conditions for synthesis of the compounds (V) wherein T 1 is -SR 3 wherein R 3 is alkyl, the compounds represented by the formula (X) may be obtained. The compounds wherein T 1 is -OR 3 wherein R 3 is alkyl are as well as the above. wherein R 5 , R 6 , R F , R G , Q 1 , X, Y, and Z are as defined above; R 3 is alkyl. The compounds represented by the formulae (VI), (VII), and (VIII) are as well as the above. In this specification, the compounds of formula (I) wherein R B and R C are different, are represented as an optical active compound by the formulae (I') and (I"). wherein R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R B , R C , X, Y, and Z are as defined above. The compounds represented by the formulae (II), (III), (IV), (V), (VI), (VII), and (VIII) are as well as the above. Best Mode for Carrying Out the Invention The compounds of the present invention represented by the formulae (I), (V), or (XIII) can be synthesized by the well-known methods described in a literature of chemistry. A summary of the useful methods for synthesis of the compounds of the present invention is shown below. wherein R 5 , R 6 , R B , R C , X, Y, and Z are as defined above; R 13 is a protective group of a hydroxy group such as methyl, ethyl, trimethylsilyl, and tert-butyldimethylsilyl or hydrogen atom; Q 3 is -NR 1 R 2 , -OR 1 , or -SR 1 ; T 3 is -NR 3 R 4 , -OR 1 , or -SR 1 wherein R 1 , R 2 , R 3 , and R 4 are as defined above. The compound represented by the formula (XIII) can be synthesized by reacting Z-Y-XH (XI) with the pyrimidine derivatives (XII) mentioned later such as (XII-1) to (XII-4). The pyrimidine derivatives (XII) in a solvent such as water, acetic acid, and pyridine are treated with a hydrohalogenic acid such as hydrochloric acid and hydrobromic acid to give hydrogen halide salts of 5-halogenomethylpyrimidine. When R 13 is hydrogen atom, a halogenation agent such as thionyl halide and phosphorous halide can be used. The obtained salts and Z-Y-XH (XI) in a solvent such as water, methanol, ethanol, N,N-dimethylformamide, dimethylsulfoxide, and tetrahydrofuran are reacted with an appropriate base, for example an inorganic base such as sodium hydroxide, potassium butoxide, sodium hydride, potassium hydride, and potassium carbonate or an organic base such as triethylamine, pyridine, and diisopropylethylamine at -20 °C to 100 °C, preferably 0 °C to 30 °C for 1 min to 24 h, preferably 10 min to 12 h to give the aimed compound (XIII). Compound (XI) and compound (XII) can be synthesized by the methods A to I and the methods J to N as shown below. In the methods A to I, Z represents optionally substituted aryl or optionally substituted heteroaryl. The starting material of each method is commercially available or can be synthesized by well-know method from the compound which is commercially available. Method A: Synthetic method of the compound wherein Y is an oxadiazole ring and X is -S-. wherein Z is above defined. Compound (XIV) in a solvent such as ethanol and benzene is reacted with carbon disulfide and a base such as triethylamine, sodium hydroxide, and potassium carbonate at 0 °C to 100 °C, preferably 60 °C to 100 °C for 10 min to 24 h, preferably 2 h to 12 h to give compound (XV-1). Method B : Synthetic method of the compound wherein Y is an oxadiazole ring and X is -O-. wherein Z is above defined. To a solution of compound (XIV) in a solvent such as tetrahydrofuran and toluene, is added carbonyldiimidazole, and the mixture is reacted at 0 °C to 120 °C, preferably 60 °C to 120 °C for 10 min to 24 h, preferably 2 h to 12 h to give compound (XV-2). Method C : Synthetic method of the compound wherein Y is an oxadiazole ring and X is -N(R 7 )-. wherein Z is as defined above and R 7 is as defined above. To a solution of compound (XVI) in a solvent such as ethanol and tetrahydrofuran, is added mercury oxide, and the mixture is reacted at 0 °C to 120 °C, preferably 30 °C to 80 °C for 0.5 h to 24 h, preferably lh to 24 h to give compound (XV-3). Method D : Synthetic method of the compound wherein Y is a thiadiazole ring and X is -S-. wherein Z is as defined above. To a solution of compound (XIV) in a solvent such as ethanol and tetrahydrofuran are added carbon disulfide and a base such as triethylamine and sodium hydroxide and the mixture is reacted at 0 °C to 100 °C, preferably 20 °C to 60 °C for 0.5 h to 24 h, preferably 1 h to 12 h. After the solvent is removed, the residue is reacted with conc. sulfuric acid at -20 °C to 40 °C, preferably 0 °C to 20 °C for 1 min to 12 h, preferably 10 min to 1 h to give compound (XV-4). Method E : Synthetic method of the compound wherein Y is a furan ring and X is -S-. wherein Z is as defined above. (Step 1) Halogenated furan such as 2-bromofuran is reacted with compound (XVII) in a solvent such as N,N-dimethylformamide, toluene, xylene, benzene, tetrahydrofuran, and ethanol in the presence of palladium catalyst such as Pd(Ph 3 P) 4 and a base such as potassium carbonate, calcium carbonate, triethylamine, and sodium methoxide to give the aimed compound (XVIII) (Suzuki reaction). The reaction temperature is room temperature to 100 °C, preferably room temperature to 80 °C and the reaction time is 5 to 50 h, preferably 15 to 30 h. (Step 2) To a solution of compound (XVIII) in a solvent such as tetrahydrofuran, diethyl ether, and toluene is added a base such as n-butyllithium and sec-butyllithium, and the mixture is stirred at -100 °C to 50 °C, preferably -80 °C to 0 °C for 1 min to 24 h, preferably 10 min to 60 min. To the mixture is added sulfur, and the resulting mixture is reacted at -100 °C to 50 °C, preferably -80 °C to 0 °C for 1 h to 24 h, preferably 1 h to 12 h to give the aimed compound (XV-5). Method F: Synthetic method of the compound wherein Y is a thiophene ring and X is -S-. wherein Z is as defined above and Hal is halogen. The steps 1 and 2 can be carried out in a manner similar to those described in step 1 and 2 of Method E. Method G : Synthetic method of the compound wherein Y is an oxazole ring and X is -S-. wherein Z is as defined above. To a solution of compound (XX) in a solvent such as dichloromethane, toluene, and diethyl ether is added thiophosgene in the presence of a base such as triethylamine and sodium hydroxide and the mixture is reacted at -20 °C to 100 °C, preferably 0 °C to 40 °C for 1 h to 48 h, preferably 1 h to 24 h to give compound (XV-7). Method H : Synthetic method of the compound wherein Y is an oxazole ring and X is -O- or -S-. wherein Z is as defined above. (Step 1) Compound (XXI) in a solvent such as dichloromethane and acetonitrile is reacted with a coupling reagent such as dicyclohexylcarbodiimide at -20 °C to 50 °C, preferably 0 °C to 20 °C for 5 min to 24 h, preferably 10 min to 2 h to give compound (XV-8). (Step 2) To a solution of compound (XV-8) in a solvent such as toluene and dioxane is added Lawesson's reagent, and the mixture is reacted at 60 °C to 150 °C, preferably 80 °C to 120 °C for 1 h to 24 h, preferably 2 to 12 h to give compound (XV-9). Method I: Synthetic method of the compound wherein Y is an isoxazole ring and X is -O- or -S-. wherein Z is as defined above and R 14 is C1 to C3 alkyl. (Step 1) Compound (XXII) in a solvent such as methanol and tetrahydrofuran is reacted with hydroxylamine at 20 °C to 100°C, preferably 50 °C to 80 °C for 1 h to 24 h, preferably 2 h to 12 h to give compound (XV-10). (Step 2) Compound (XV-11) can be obtained in a manner similar to that described in step 2 of Method H. The compounds which are not concretely shown in the above methods can be synthesized by a combination of the above methods A to I and well-know methods. In the methods J to N, R 5 , R 6 , R 13 , Q 3 , and T 3 (wherein R 1 , R 2 , R 3 , and R 4 are as defined above) are as defined above. The starting material of each method is commercially available or can be synthesized by well-know methods from the compound which is commercially available. Methods J and K are processes for construction of a pyrimidine ring, and can be carried out in accordance with well-known methods (see Journal of Chemical Society, 1937, p-364, ibid., 1943, p-388 and J. Pharm. Soc. Japan 1954, p-742). Methods L to N are processes for introduction a guanidino group to the pyrimidine derivative obtained in the Method J and Method K, and can be carried out in accordance with well-known methods (see Journal of Chemical Society, 1948, p-581, ibid., 1946, p-1063 and Synthesis, 1988, p-460). Method J-1 : Synthesis of a pyrimidine ring wherein both R X and R Y are hydrogen atom. wherein R 5 , R 6 and R 13 are as defined above; and R X and R Y are hydrogen atom. (Step 1) Compound (XXIII) in a solvent such as ethanol, tetrahydrofuran, and N,N-dimethylformamide is reacted with R 5 -C(=S)-NH 2 in the presence of a base such as sodium ethylate and sodium hydroxide at 0 °C to 150 °C, preferably 60 °C to 100 °C for 0.5 h to 48 h, preferably 1 h to 12 h to give compound (XXIV). (Step 2) Compound (XXIV) in a solvent such as ether and tetrahydrofuran or in a mixed solvent such as ether-tetrahydrofuran is reacted with a reducing agent such as lithium aluminum hydride and lithium borohydride at -80 °C to 100 °C, preferably -20 °C to 40 °C for 0.5 h to 24 h, preferably 1 h to 12 h to give an alcohol derivative. The obtained alcohol derivative is protected by the method described in Protective Groups in Organic Synthesis, Theodora W Green (John Wiley & Sons) and the like, to give compound (XXV). Method J-2 : Synthesis of a pyrimidine ring wherein one of R X and R Y is hydrogen atom. wherein R 5 , R 6 and R 13 are as defined above; R X is alkyl; and R Y are hydrogen atom or alkyl. (Step 1) Compound (XXIV) in a solvent such as ether and tetrahydrofuran or in a mixed solvent such as ether-tetrahydrofuran is reacted with a reducing agent such as lithium aluminum hydride and lithium borohydride at -80 °C to 100 °C, preferably -20 °C to 40 °C for 0.5 h to 24 h, preferably 1 h to 12 h to give compound (XXVI). (Step 2) Compound (XXVI) in a solvent such as dichloromethane and chloroform is reacted with a oxidizing agent such as manganese dioxide, pyridinium dichromate, and pyridinium chlorochromate at -20 °C to 100 °C, preferably 0 °C to 40 °C for 0.5 h to 14 days, preferably 1 h to 7 days to give an aldehyde derivative. The obtained aldehyde derivative in a solvent such as ether and tetrahydrofuran or in a mixed solvent such as ether-tetrahydrofuran is reacted with Grignard reagent such as R X MgBr or organometallic reagent such as R X Li at -80 °C to 100 °C, preferably -20 °C to 40 °C for 0.5 h to 24 h, preferably 1 h to 12 h to give an alcohol derivative. The obtained alcohol derivative is protected by the method described in Protective Groups in Organic Synthesis, Theodora W Green (John Wiley & Sons) and the like, to give compound (XXV). Method J-3 : Synthesis of a pyrimidine ring wherein both of R X and R Y are not hydrogen atom. wherein R 5 , R 6 and R 13 are as defined above; R X and R Y are each independently alkyl or alkyloxy; R 15 is alkyl such as methyl and ethyl. (Step 1) Compound (XXVII) in a solvent such as ethanol, tetrahydrofuran, and N,N-dimethylformamide is reacted with R 5 -C(=N)-NH 2 in the presence of a base such as sodium ethylate and sodium hydroxide, at 0 °C to 150 °C, preferably 60 °C to 100 °C for 0.5 h to 48 h, preferably 1 h to 12 h to give compound (XXVIII). (Step 2) Compound (XXVIII) in a solvent such as ether and tetrahydrofuran or in a mixed solvent such as ether-tetrahydrofuran is reacted with Grignard reagent such as R X MgBr or organometallic reagent such as R X Li at -80 °C to 100 °C, preferably -20 °C to 40 °C for 0.5 h to 24 h, preferably 1 h to 12 h. To the mixture an acid aqueous solution such as hydrochloric acid and sulfuric acid is added, and then the resulting mixture is stirred at -20 °C to 100 °C, preferably 0 °C to 40 °C for 0.5 h to 24 h, preferably 1 h to 12 h to give compound (XXIX). (Step 3) Compound (XXIX) in a solvent such as ether and tetrahydrofuran or in a mixed solvent such as ether-tetrahydrofuran is reacted with Grignard reagent such as R X MgBr or organometallic reagent such as R X Li at -80 °C to 100 °C, preferably -20 °C to 40 °C for 0.5 h to 24 h, preferably 1 h to 12 h to give an alcohol derivative. The obtained alcohol derivative is protected by the method described in Protective Groups in Organic Synthesis, Theodora W Green (John Wiley & Sons) and the like, to give compound (XXX). Method J-4 : Synthesis of a pyrimidine ring wherein R X and R Y are same. wherein R 5 , R 6 and R 13 are as defined above; R X and R Y are same as alkyl or alkyloxy. (Step 1) Compound (XXIV) in a solvent such as ether and tetrahydrofuran or in a mixed solvent such as ether-tetrahydrofuran is reacted with Grignard reagent such as R X MgBr or organometallic reagent such as R X Li at -80 °C to 100 °C, preferably -20 °C to 40 °C for 0.5 h to 24 h, preferably 1 h to 12 h to give an alcohol derivative. The obtained alcohol derivative is protected by the method described in Protective Groups in Organic Synthesis, Theodora W Green (John Wiley & Sons) and the like to give compound (XXV). Method J-5 : Synthesis of a pyrimidine ring wherein one of R X and R Y is hydrogen atom. wherein R 5 , R 6 and R 13 are as defined above; one of R X and R Y is hydrogen atom and the other is hydrogen atom, alkyl or alkyloxy. (Step 1) Compound (XXVIII) in a solvent such as ether and tetrahydrofuran or a mixed in solvent such as ether-tetrahydrofuran is reacted with Grignard reagent such as R X MgBr or organometallic reagent such as R X Li at -80 °C to 100 °C, preferably -20 °C to 40 °C for 0.5 h to 24 h, preferably 1 h to 12 h. To the mixture an acid aqueous solution such as hydrochloric acid and sulfuric acid is added, and then the resulting mixture is stirred at -20 °C to 100 °C, preferably 0 °C to 40 °C for 0:5 h to 24 h, preferably 1 h to 12 h to give compound (XXIX). (Step 2) Compound (XXIX) in a solvent such as ether, tetrahydrofuran, methanol, and ethanol or their mixed solvent is reacted with a reducing agent such as sodium borohydride , lithium borohydride, and lithium aluminum hydride at -80 °C to 100 °C, preferably -20 °C to 40 °C for 0.5 h to 24 h, preferably 1 h to 12 h to give an alcohol derivative. The obtained alcohol derivative is protected by the method described in Protective Groups in Organic Synthesis, Theodora W Green (John Wiley & Sons) and the like to give compound (XXV). Method K : Synthesis of a pyrimidine ring. wherein R 1 , R 5 , R 6 and R 13 are as defined above. (Step 1) Compound (XXVI) in a solvent such as ethanol, tetrahydrofuran, and N,N-dimethylformamide is reacted with R 5 -C(=NH)-NH 2 or its salt in the presence of a base such as sodium ethylate and sodium hydroxide at 0 °C to 150 °C, preferably 60 °C to 100 °C for 0.5 h to 48 h, preferably 1 h to 12 h to give compound (XXVII) or its salt. (Step 2) Compound (XXVII) or its salt in a solvent such as toluene and dichloroethane or without solvent is reacted with a halogenating reagent such as thionyl chloride and phosphorus oxychloride at 0 °C to 150 °C, preferably 60 °C to 120 °C for 0.5 h to 12 h, preferably 1 h to 5 h to give a halogenated compound. The obtained halogenated compound in a solvent such as ethanol and tetrahydrofuran is reacted with R 1 NH 2 at -80 °C to 100 °C, preferably -20 °C to 30 °C for 0.5 h to 48 h, preferably 1 h to 12 h to give compound (XXVIII). (Step 3) This step can be carried out in a manner similar to that described in step 2 of Method J-1. Method L : Introduction of a guanidino group wherein R 1 , R 2 , R 3 , R 4 , R 5 , R 6 and R 13 are as defined above. (Step 1) Compound (XXV) in a solvent such as N,N-dimethylformamide, pyridine, and tetrahydrofuran is reacted with R 3 -NCS or R 3 R 4 NCS-Hal wherein Hal is halogen, in the presence or absence of a base such as sodium hydride at -20 °C to 120 °C, preferably 0 °C to 120 °C for 0.5 h to 48 h, preferably 1 h to 24 h to give compound (XXIX). (Step 2) To a solution of compound (XXIX) in a solvent such as methanol and tetrahydrofuran are added a heavy metal salt or heavy metal oxide such as HgO and R 1 R 2 NH, and the mixture is reacted at -20 °C to 100 °C, preferably 0 °C to 50 °C for 0.5 h to 48 h, preferably 1 h to 12 h to give compound (XII-1). Method M : Introduction of a guanidino group wherein R 1 , R 3 , R 4 , R 5 , R 6 and R 13 are as defined above. (Step 1) To a solution of compound (XXV) in a solvent such as N,N-dimethylformamide and tetrahydrofuran in the presence of a base such as sodium hydride and potassium butoxide added carbon disulfide and then alkylating reagent such as R 1 I and R 1 2 SO 4 , and the mixture is reacted at 0 °C to 100 °C, preferably 20 °C to 60 °C for 0.5 h to 48 h, preferably 1 h to 12 h to give compound (XII-2). (Step 2) Compound (XII-2) in a solvent such as methanol and N,N-dimethylformamide is reacted with R 3 R 4 NH at 0 °C to 150 °C, preferably 0 °C to 100 °C for 0.5 h to 48 h, preferably 1 h to 12 h to give compound (XII-3). (Step 3) Compound (XII-3) in a solvent such as methanol and N,N-dimethylformamide is reacted with R 1 R 2 NH at 20 °C to 150 °C, preferably 40 °C to 80 °C for 0.5 h to 48 h, preferably 4 h to 24 h to give compound (XII-4). Method N : Introduction of a guanidino group wherein R 1 is not hydrogen atom. wherein R 1 , R 2 , R 3 , R 4 , R 5 , R 6 and R 13 are as defined above. (Step 1) This step can be carried out in a manner similar to that described in step 1 of Method L. (Step 2) This step can be carried out in a manner similar to that described in step 2 of Method L. When a compound contains a functional group(s) possibly interfering the reaction such as hydroxy, mercapto, and amino group in the each step of Method A to Method N, it can previously be protected and deprotected at an appropriate stage by the method described Protective Groups in Organic Synthesis, Theodora W. Green (John Wiley & Sons). The term "the compounds of the present invention" herein used includes pharmaceutically acceptable salts and hydrates of the compounds. For example, salts with alkali metals (e.g., lithium, sodium, and potassium), alkaline earth metals (e.g., magnesium and calcium), ammonium, organic bases, amino acids, mineral acids (e.g., hydrochloric acid, hydrobromic acid, phosphoric acid, and sulfuric acid), or organic acids (e.g., acetic acid, citric acid, maleic acid, fumaric acid, benzenesulfonic acid, and p-toluenesulfonic acid) are exemplified. These salts can be formed by usual methods. The hydrates may coordinate with an arbitrary number of water molecule. The compounds of the present invention is not restricted to any particular isomers but includes all possible isomers and racemate. The compounds of the present invention have an inhibitory activity against a signal derived from Ras oncogene products as shown in the experimental examples below. Consequently, the compounds of the present invention can be used as a therapeutic agent for cancer, preferably solid tumor such as pancreatic cancer, colon cancer, and lung cancer. When the compounds of this invention is administered to a patient for the treatment of the above diseases, they can be administered by oral administration such as powder, granules, tablets, capsules, pilulae, liquid medicine, or the like , or by parenteral administration such as injections, suppository, percutaneous formulations, insufflation, or the like. An effective amount of the compound of this invention is formulated by being mixed with appropriate medicinal admixture such as excipient, binder, penetrant, disintegrators, lubricant, and the like, if necessary. When parenteral injection is prepared, the compound of this invention and an appropriate carrier are sterilized to formulate. An appropriate dosage varies with the conditions of the patients, an administration route, their age, and their body weight. In the case of oral administration to an adult, the dosage can generally be between 0.01 100 mg/kg/day, preferably 0.1 - 20 mg/kg/day. The following examples are provided to further illustrate the present invention and are not to be construed as limiting the scope thereof. In the examples, the following abbreviations are used. Me : methyl Et : ethyl Pr n-propyl i-Pr : isopropyl Bu : n-butyl DMF : dimethylformamide THF : tetrahydrofuran DMSO : dimethylsulfoxide TBS : tert-butyldimethylsilyl TBDPS ; tert-butyldiphenylsilyl In 1 H-NMR, the value of δ is represented by ppm, s is singlet, d is doublet, t is triplet, q is quartet, quit is quintet, sext is sextet, and br is broad. The value of J is represented by Hz. Example Example 1 Step 1 To a solution of potassium t-butoxide (8.05 g) in 60 ml of DMF was added dropwise a solution of compound 1 (10.0 g) which was obtained by well-known method (M. Tomita, S. Uyeo, A. Takamizawa and R. Maeda, Yakugakuzasshi, 74, 742 (1954)), in 29 ml of DMF with stirring at ice-cooling. The reaction mixture was allowed to room temperature and stirred for 1 h. To the resulting mixture was added a solution of methylisothiocyanate (5.25 g) in 7.5 ml of DMF at ice-cooling and stirred for 2 h at room temperature. After confirming the disappearance of compound 1, a solution of methyl iodide (12.7 g) in 1.5 ml of DMF was added to the mixture at ice-cooling. The mixture was stirred for 1 h at room temperature and DMF was removed under reduced pressure, and then water was added to the residue. The mixture was extracted with diethyl ether, washed with brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography to give 8.15 g of compound 2. 1 H-NMR(CDCl 3 ): 1.26(3H, t, J=6.9 Hz), 2.52(3H, s), 2.56(3H, s), 3.07(3H, d, J=5.3 Hz), 3.60(2H, q, J=6.9 Hz), 4.61(2H, s), 8.41(1H, s). Step 2 A solution of compound 2 (2.50 g) in 25 ml of 25% hydrobromic acid/acetic acid was reacted for 7 h at 70 °C. The solvent was removed under reduced pressure, and the residue was dissolved in 10 ml of DMF. The resulting mixture was added to a suspension of 2-(4-nitrophenyl)-5-mercapto-1,3,4-oxadiazole (2.41 g) which was obtained in similar to described (R. W. Young and K. H. Wood. J. Am. Chem. Soc., 77, 400 (1955)) and potassium carbonate (5.43 g) in 25 ml of DMF. The reaction mixture was stirred for 1 h at room temperature and added water. The appeared crystal was filtered to give 2.56 g of compound A-1 . The physical data was shown in Table 1. Example 2 to 17 Compounds A-2 to A-17 were synthesized in a manner similar to described in Example 1. The physical data were shown in Tables 1 to 2. Example 18 Step 1 To a solution of potassium t-butoxide (3.43 g) in 30 ml of DMF was added dropwise a solution of compound 1 (4.64 g) in 12 ml of DMF with stirring at ice-cooling. The reaction mixture was allowed to room temperature and stirred for 30 min. To the resulting mixture was added dropwise a solution of propylisothiocyanate (3.09 g) in 3 ml of DMF at ice-cooling and stirred for 1.5 h at room temperature. After confirming the disappearance of compound 1 , a solution of methyl iodide (5.91 g) in 3 ml of DMF was added to the mixture at ice-cooling. The mixture was stirred for 1 h at room temperature. DMF was removed under reduced pressure and added water. The resulting mixture was extracted with diethyl ether, washed with brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. To the residue was added hexane, the appeared crystal was filtered to give 2.25 g of compound 3 . 1 H-NMR(CDCl 3 ) :1.06(3H, t, J=7.3 Hz), 1.27(3H, t, J=7.3 Hz), 1.71(2H, sext, J=7.3 Hz), 2.51(3H, s), 2.55(3H, s), 3.35(2H, q, J=7.3 Hz), 3.60(2H, q, J=7.3 Hz), 4.61(2H, s), 8.41(1H, s), 11.31(1H, br). Step 2 A solution of compound 3 (0.10 g) and dimethylhydrazine (0.43 g) in 2 ml of ethanol was stirred for 3 days at 65 °C. The reaction mixture was concentrated under reduced pressure, and the residue was subjected to silica gel column chromatography to give 0.03 g of compound 4 . 1 H-NMR(CDCl 3 ): 0.96(3H, t, J=7.3 Hz), 1.26(3H, t, J=7.3 Hz), 1.62(2H, sext, J=7.3 Hz), 2.50(3H, s), 2.61(6H, s), 3.37(2H, q, J=7.3 Hz), 3.60(2H, q, J=7.3 Hz), 4.53(2H, s), 6.25(1H, br), 8.21(1H, s), 10.94(1H, br). Step 3 A solution of compound 4 (0.03 g) in 0.3 ml of 25% hydrobromic acid in acetic acid was reacted for 7 h at 70 °C. The solvent was removed under reduced pressure, and the residue was dissolved in 1 ml of DMF. The resulting mixture was added to a suspension of 2-(4-nitrophenyl)-5-mercapto-1,3,4-oxadiazole (0.03 g) and potassium carbonate (0.06 g) in 2 ml of DMF. The reaction mixture was stirred for 1 h at ice-cooling and added water. The appeared crystal was filtered and recrystalized from ethyl acetate/hexane to give 0.02 g of compound A-18 . The physical data were shown in Table 2. Example 19 Compounds A-19 was synthesized in a manner similar to described in Example 18. The physical data were shown in Table 3. Example 20 Step 1 To a solution of potassium t-butoxide (0.73 g) in 15 ml of DMF was added dropwise a solution of compound 1 (1.00 g) in 5 ml of DMF with stirring at ice-cooling. To the resulting mixture was added dropwise 3-t-butyldiphenylsilyloxypropylisothiocyanate (2.33 g) which was obtained easily from 3-amino-1-propanol by usual method and stirred for 17 h. To the reaction mixture was added water, and the mixture was extracted with diethyl ether, washed with brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography to give 1.10 g of compound 5 . 1 H-NMR(CDCl 3 ) : 1.05(9H, s), 1.36(3H, t, J=6.9 Hz), 1.98(2H, quint, J=6.6 Hz), 2.42(3H, s), 3.63(2H, q, J=6.9 Hz), 3.81(2H, t, J=6.6 Hz), 3.89(2H, q, J=6.6 Hz), 4.51(2H, s), 7.31 - 7.41(6H, m), 7.64 - 7.68(4H, m), 8.22(1H, s), 9.40(1H, br), 11.48(1H, br). Step 2 A solution of compound 5 (1.00 g) and p-toluenesulfonic acid monohydrate (0.76 g) in 5 ml of toluene was heated with stirring for 2 h under reflux. To the resulting mixture were added water and saturated sodium hygrogencarbonate aqueous solution. The mixture was extracted with ethyl acetate, washed with brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography to give 0.25 g of compound 6. 1 H-NMR(CDCl 3 ) 1.26(3H, t, J=6.9 Hz), 2.13 2.21(2H, m), 2.54(3H, s), 3.07 - 3.12(2H, m), 3.55 - 3.62(2H, m), 3.61(2H, q, J=6.9 Hz), 4.57(2H, s), 8.38(1H, s), 11.81(1H, br). Step 3 A solution of compound 6 (0.10 g) in 0.8 ml of 25% hydrobromic acid/acetic acid was reacted for 14 h at 70 °C. The solvent was removed under reduced pressure, and the residue was dissolved in 1 ml of DMF. The resulting mixture was added to a suspension of 2-(4-nitrophenyl)-5-mercapto-1,3,4-oxadiazole (0.09 g) and potassium carbonate (0.21 g) in 2 ml of DMF at ice-cooling. The reaction mixture was stirred for 1 h at ice-cooling and added water. The appeared crystal was filtered and recrystalized from dichloromethane/diethyl ether/hexane to give 0.07 g of compound A-20. The physical data were shown in Table 3. Example 21 Compounds A-21 was synthesized in a manner similar to described in Example 20. The physical data were shown in Table 3. Example 22 Step 1 To a suspension of lithium aluminum hydride (4.4 g) in 220ml of THF was added dropwise a solution of 4-amino-5-ethoxycarbonyl-2-methylpyrimidine 7 (22.0 g) which was obtained by the method described in literature (G. W. Kenner, B. Lythgoe, A. R. Todd and A. Topham. J. Chem. Soc., 388 (1943)) in 220 ml of THF with stirring at ice-cooling. The reaction mixture was allowed to room temperature and stirred for 2 h. To the mixture was added excess of ice and the stirring was continued for additional 2 h. To the reaction mixture was added anhydrous sodium sulfate, and the stirring was continued. The THF-insoluble material was filterd off and washed with methanol. The combined filtrate was concentrated completely under reduced pressure and added ethanol. The ethanol solution was heated and the insoluble material was filtered off. The ethanol-soluble filtrate was cooled and the appeared insoluble material was filtered off again. The filtrate was diluted with diethyl ether and the appeared crystals were filterd to give 14.5 g of compound 8 . Melting Point :191∼192°C, 1 H-NMR(DMSO-d 6 ) 2.28(3H, s), 4.30(2H, s), 7.90(1H, s). Step 2 To a solution of compound 8 (500 mg) in a combined solvent of 10 ml of dichloromethane and 5 ml of methanol was added active manganese dioxide (2.5 g), and stirred for 6 days at room temperature. The dichloromethane-insoluble material was filtered off and the solvent was removed under reduced pressure. The residue was subjected to silica gel column chromatography and crystalized from diethyl ether to give 284 mg of compound 9 . 1 H-NMR(CDCl 3 ): 2.58(3H, s), 5.84(1H, br), 8.13(1H, br), 8.57(1H, s), 9.86(1H, s). Step 3 A solution of compound 9 (280 mg) in 14 ml of THF was heated to dissolve and the mixture was allowed to ice-cooling. To the mixture was added dropwise 0.93 M solution of methylmagnesium bromide in THF (8.8 ml) with stirring at ice-cooling. The reaction mixture was stirred for 20 min at room temperature. Ice-water was added to the mixture, and the mixture was extracted with ethyl acetate. And the aqueous layer was rextracted with methyl ethyl ketone. The combined organic layer was concentrated under reduced pressure, and 10% solution of metanol in dichloromethane was added to the residue, then the insolble material was filtered off. The filtrate was subjected to silica gel column chromatography and then crystalized from diethyl ether/hexane to give 188 mg of compound 10. 1 H-NMR(CDCl 3 ): 1.57(3H, d, J=6.6 Hz), 2.13(1H, br), 2.48(3H, s), 4.86(1H, q, J=6.6 Hz), 5.55(2H, br), 7.94(1H, s). Step 4 A solution of compound 10 (188 mg) and imidazole (100 mg) in 10 ml of DMF was added a solution of t-butyldimethylchlorosilane (200 mg) in 2 ml of DMF with stirring at ice-cooling. The mixture was stirred at room temperatuer for 2 h, and then imidazole (50 mg) and t-butyldimethylchlorosilane (100 mg) were added again to the mixture. The reaction mixture was stirred overnight, and added ethyl acetate. The resulting mixture was washed with brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography to give 285 mg of compound 11 . 1 H-NMR(CDCl 3 ): 0.01(3H, s), 0.10(3H, s), 0.88(9H, s), 1.46(3H, d, J=6.6 Hz), 2.48(3H, s), 4.79(1H, q, J=6.6 Hz), 5.56(2H, br), 7.87(1H, s). Step 5 Potassium t-butoxide (140 m g) was added to a solution of compound 11 (285 mg) in 5.0 ml of DMF with stirring at ice-cooling. After stirring for 5 min, ethylisothiocyanate (0.11 ml) was added dropwise. The resulting mixture was stirred for 10 min at ice-cooling and methyl iodide (0.08 ml) was added, and stirred for additional 1 h. To the reaction mixture was added water, extracted with ethyl acetate, washed with brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography to give 176 mg of compound 12 . 1 H-NMR(CDCl 3 ) : -0.01(3H, s), 0.05(3H, s), 0.90(9H, s), 1.33(3H, t, J=7.3 Hz), 1.40(3H, d, J=6.3 Hz), 2.48(3H, s), 2.55(3H, s), 3.42(2H, dq, J=5.6 Hz, 7.3 Hz), 5.36(1H, q, J=6.3 Hz), 8.54(1H, s), 11.18(1H, br). Step 6 A solution of compound 12 (50 m g) in 1.0 ml of 25% hydrobromic acid/acetic acid was reacted for 15 h at 40 °C. The solvent was removed under reduced pressure, and the residue was dissolved in 1 ml of DMF. The resulting mixture was added to a suspension of 2-(4-nitrophenyl)-5-mercapto-1,3,4-oxadiazole (50 mg) and potassium carbonate (105 mg) in 2 ml of DMF at ice-cooling. The reaction mixture was stirried for 1 h at ice-cooling and added water. The reaction mixture was extracted with dichloromethane, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography and crystalized from diethyl ether to give 16.8 mg of compound A-22 . The physical data were shown in Table 3. Example 23 Step 1 To a solution of compound 12 (120 mg) in 3.0 ml of ethanol was added 70% ethylamine aqueous solution (0.27 ml), and the mixture was stirred for 5 h at 60 °C. An additional 70% ethylamine aqueous solution (0.54 ml) was added to the reaction mixture, stirred overnight at 80 °C. After cooling, the solvent was removed under reduced pressure to give 114 mg of compound 13 . 1 H-NMR(CDCl 3 ) -0.00(3H, s), 0.04(3H, s), 0.91(9H, s), 1.28(6H, t, J=7.2 Hz), 1.39(3H, d, J=6.2 Hz), 2.48(3H, s), 3.33(4H, br), 5.27(1H, q, J=6.2 Hz), 8.35(1H, s). Step 2 A solution of compound 13 (50 m g) in 1.0 ml of 25% hydrobromic acid/acetic acid was reacted for 15 h at 40 °C. The solvent was removed under reduced pressure, and the residue was dissolved in 1 ml of DMF. The resulting mixture was added to a suspension of 2-(4-nitrophenyl)-5-mercapto-1,3,4-oxadiazole (50 mg) and potassium carbonate (105 mg) in 2 ml of DMF at ice-cooling. The reaction mixture was stirred for 3 h at ice-cooling and added water. The mixture was extracted with dichloromethane and successively with 20% 2-propanol/dichlorometane, and the combined organic layer was dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography and crystalized from methanol to give 24.9 mg of compound A-23 . The physical data were shown in Table 3. Example 24 Step 1 To a solution of compound A-1 (100 mg) in a mixed solvent of dichoromethane (5.0 ml) and methanol(5.0 ml) was added silver(I) oxide (70 mg), and the reaction mixture was stirred for 4 h at room temperature. The dicholomethane-insoluble material was filtered off and the filtrate was concentrated under reduced pressure. The residue was subjected to silica gel column chromatography and recrystalized from diethyl ether to give 82.9 mg of compound A-24 . The physical data were shown in Table 3. Example 25 to 27 Compounds A-25 to A-27 were synthesized in a manner similar to described in Example 24. The physical data were shown in Table 3. Example 28 Step 1 To a solution of potassium t-butoxide (3.69 g) in 20 ml of DMF was added dropwise a solution of compound 1 (5.00 g) in 32 ml of DMF with stirring at ice-cooling. The reaction mixture was allowed at room temperature and stirred for 30 min. A solution of ethylisocyanate (2.34 g) in 6 ml of DMF was added dropwise to the mixture at ice-cooling, and the mixture was stirred for 1.5 h at room temperature. After removal of DMF under reduced pressure, water was added to the residure. The mixture was extracted with diethyl ether, washed with brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography to give 6.27 g of compound 14. 1 H-NMR(CDCl 3 ): 1.26(3H, t, J=7.3 Hz), 1.27(3H, t, J=7.3 Hz), 2.60(3H, s), 3.43(2H, dq, J=5.6 Hz, 7.3 Hz), 3.55(2H, q, J=7.3 Hz), 4.46(2H, s), 7.99(1H, br), 8.17(1H, s), 9.36(1H, br). Step 2 A solution of compound 14 (100 m g) in 2.5 ml of 25% hydrobromic acid in acetic acid was reacted for 5 h at 70 °C. The solvent was removed under reduced pressure, and the residue was dissolved in 2 ml of DMF. The resulting mixture was added to a suspension of 2-(4-nitrophenyl)-5-mercapto-1,3,4-oxadiazole (120 mg) and potassium carbonate (230 mg) in 3 ml of DMF at ice-cooling. The reaction mixture was stirred for 1 h at ice-cooling, then water was added to the reaction mixture. The insolble precipitate was filtered, dried, and subjected to silica gel column chromatography and crystalized from methanol to give 126 mg of compound B-1 . The physical data were shown in Table 5. Example 29 to 31 Compounds B-2 to B-4 were synthesized in a manner similar to described in Example 28. The physical data were shown in Table 5. Example 32 Step 1 A solution of compound 1 (2.24 g) in 30 ml of 25% hydrobromic acid/acetic acid was reacted for 15.5 h at 70 °C. The solvent was removed under reduced pressure, and the residue was dissolved in 10 ml of DMF. The resulting mixture was added to a suspension of 2-(4-nitrophenyl)-5-mercapto-1,3,4-oxadiazole (3.13 g) and potassium carbonate (7.14 g) in 35 ml of DMF at ice-cooling. The reaction mixture was stirred for 1 h at ice-cooling and added water. The appeared crystal was filtered to give 3.99 g of compound 15 . 1 H-NMR(DMSO-d 6 ): 2.28(3H, s), 4.37(2H, s), 7.09(2H, br), 7.67(2H, d, J=8.6 Hz), 7.98(2H, d, J=8.6 Hz), 8.06(1H, s). Step 2 To a solution of compound 15 (200 mg) in 10 ml of DMF was added potassium t-butoxide (70 mg) with stirring at colling with dryice/acetonitrile bath. The reaction mixture was stirred for 5 min and ethylisothiocyanate (0.06 ml) was added to the resulting mixture. The reaction mixture was stirred for 3 min and added acetic acid (0.05 ml). To the reaction mixture was added water at room temperature, extracted with dichloromethane, washed with brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography and crystalized from diethyl ether to give 16.3 mg of compound B-5 . The physical data were shown in Table 5. Example 33 Step 1 To a solution of compound 15 (200 mg) in 10 ml of DMF were added potassium t-butoxide (140 mg) and carbon disulfide (0.04 ml) with stirring at cooling with dryice/acetonitrile bath. After stirring for 5 min, ethyl iodide (0.1 ml) was added. The reaction mixture was stirred for additional 15 min and water was added at room temperature. The reaction mixture was extracted with ethyl acetate, washed with brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography to give a mixture of compounds B-6, B-7, and A-28. Crystals, which were appeared by addition of diethyl ether to obtaind mixture was filtered to give 4.7 mg of compound B-6. The physical data was shown in Table 5. The filtrate was subjected again to silica gel column chromatography to separate compounds B-7 and A-28, and then independently crystalized from diethyl ether/hexane to give 2.2 mg of B-7 and 6.1 mg of A-28, respectively. The physical data of compound B-7 and A-26 were shown in Table 5 and Table 3, respectively. Example 34 to 40 Compounds A-29 to A-35 were synthesized in a manner similar to described above. The physical data were shown in Table 4. Example 41 Step 1 To a suspension of sodium hydride (2.28 g) in 50 ml of DMF was added dropwise a solution of compound 19 (5.56 g) which was obtained by the method described in WO00/04014, and carbon disulfide (3.59 g) in 60 ml of DMF with stirring at ice-cooling. The reaction mixture was allowed to room temperature and stirred for 20 min, and a solution of methyl iodide (9.34 g) in 10ml of DMF was added dropwise to the mixture at ice-cooling. The resulting mixture was stirred for 1.5 h at room temperature, and DMF was removed under reduced pressure. After addition of water the mixture was extracted with ethyl acetate, washed with brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography to give 4.45 g of compound 20 . 1 H-NMR(CDCl 3 ) 0.10(6H, s), 0.94(9H, s), 2.54(6H, s), 2.67(3H, s), 4.64(2H, s), 8.63(1H, s). Step 2 A solution of compound 20 (0.06 g) and 3-amino-1-propanol (0.02 g) in 1 ml of methanol was stirred for 16 h at 30 °C. The reaction mixture was concentrated under reduced pressure and the residue was subjected to silica gel column chromatography to give 0.06 g of compound 21. 1 H-NMR(CDCl 3 ) 0.10(6H, s), 0.95(9H, s), 1.94(2H, quint, J=6.6 Hz), 2.48(3H, s), 2.55(3H, s), 3.54(2H, q, J=6.6 Hz), 3.83(2H, t, J=6.6 Hz), 4.83(2H, s), 8.48(1H, s), 11.22(1H, br). Step 3 To a solution of compound 21 (0.06 g) in 0.5 ml of THF was added potassium t-butoxide (0.02 g) with stirring at room temperature, and the reaction mixture was stirred for 4 h. The reaction mixture was concentrated under reduced pressure and the residue was subjected to silica gel column chromatography to give 0.05 g of compound 22 . 1 H-NMR(CDCl 3 ) 0.10(6H, s), 0.94(9H, s), 2.11(2H, quint, J=5.3 Hz), 2.55(3H, s), 3.58(2H, t, J=5.3 Hz), 4.40(2H, t J=5.3 Hz), 4.79(2H, s), 8.45(1H, s), 11.38(1H, br). Step 4 A solution of compound 22 (0.04 g) and tetrabutylammonium fluoride trihydrate (0.04 g) in 1 ml of THF was stirried for 18 h at room temperature. The reaction mixture was concentrated under reduced pressure and the residue was subjected to silica gel column chromatography to give 0.02 g of crude compound 23 . This crude compound 23 was used for Step 5 without purification. Step 5 To a solution of the crude compound 22 (0.02 g) which was obtained at Step 4 in 1 ml of 1,2-dichloroethane were added thionyl chloride (0.01 g) and catalytic amount of DMF with stirring at room temperature. The mixture was stirred for 1 h at room temperature and for 10 min at 80 °C. The solvent was removed under reduced pressure and the residue was dissolved in 1 ml of DMF. The resulting mixture was added to a suspension of 2-(4-nitrophenyl)-5-mercapto-1,3,4-oxadiazole (0.02 g) which was obtained by similar method described in a literature (R. W. Young and K. H. Wood. J. Am. Chem. Soc., 77, 400 (1955)) and potassium carbonate (0.06 g) in 1ml of DMF. The reaction mixture was stirred for 1 h at room temperature and added water. The resulting mixture was extracted with ethyl acetate, washed with brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography and crystalized from methanol/diethyl ether/hexane to give 0.02 g of compound B-8. The physical data were shown in Table 5. Example 42 Step 1 A solution of compound 17 (0.95 g), which was obtained by similar method described in reference example 1, in 13 ml of 7N ammonia in methanol was reacted for 4 days at 80 °C in sealed tube. The solvent was removed under reduced pressure and added dichloromethane. The insoluble material was filtered to give 0.21 g of compound 24 . The filtrate was cocentrated under reduced pressure and the residue was subjected to silica gel column chromatography to give 0.39 g of compound 25 . Compound 24 1 H-NMR(CDCl 3 ): 1.27(3H, t, J=7.3), 2.54(3H, s), 3.60(2H, q, J=7.3 Hz), 4.09(2H, q-like, J=8.9 Hz), 4.54(2H, s), 8.34(1H, s). Compound 25 1 H-NMR(CDCl 3 ) : 1.27(3H, t, J=7.3), 2.58(3H, s), 3.61(2H, q, J=7.3 Hz), 3.94(3H, s), 3.91-3.98(2H, m), 4.59(2H, s), 8.44(1H, s), 10.73(1H, br). Step 2 A solution of compound 25 (0.10 g) in 1.0 ml of 25% hydrobromic acid/acetic acid was reacted for 7 h at 70 °C. The solvent was removed under reduced pressure, and the residue was dissolved in 1.5 ml of DMF. The resulting mixture was added to a suspension of 2-(4-nitrophenyl)-5-mercapto-1,3,4-oxadiazole (0.08 g) and potassium carbonate (0.18 g) in 1 ml of DMF at ice-cooling. The reaction mixture was stirred for 1 h at ice-cooling and added water. The appeared crystal was filtered and crystalized from methanol/dichloromethane/diethyl ether to give 0.06 g of compound B-9. The physical data were shown in Table 5. Reference Reference 1 Step 1 To a solution of compound 1 (6.00g) in 40 ml of DMF was added carbon disulfide (6.00 g) and the mixture was added dropwise to a solution of potassium t-butoxide (10.5 g) in 50 ml of DMF at ice-cooling. The reaction mixture was allowed to room temperature and stirred for 1.5 h, and then a solution of methyl iodide (15.3 g) in 10 ml of DMF was added at ice-cooling. The mixture was stirred for 1.5 h at room temperature, and then DMF was removed under reduced pressure and added water. The resulting mixture was extracted with diethyl ether, washed with brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography to give 3.05 g of compound 16 . 1 H-NMR(CDCl 3 ): 1.24(3H, t, J=7.0 Hz), 2.55(6H, s), 2.67(3H, s), 3.55(2H, q, J=7.0 Hz), 4.43(2H, s), 8.41(1H, s). Step 2 To a suspension of compound 16 (3.05 g) and 2,2,2-trifluoroethylamine hydrochloride (6.09 g) in 30 ml of DMF was added triethylamine (4.55 g) and the mixture was stirred for 4days at 50 °C. To the mixture was added water, and then mixture was extracted with diethyl ether, washed with brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography to give 2.62 g of compound 17 . 1 H-NMR(CDCl 3 ): 1.27(3H, t, J=7.3 Hz), 2.55(3H, s), 2.58(3H, s), 3.60(2H, q, J=7.3 Hz), 4.03(2H, dq, J=8.6 Hz, 6.3 Hz), 4.62(2H, s), 8.50(1H, s). Step 3 A solution of compound 17 (2.62 g) and 40% methylamine in methanol (50 ml) in 15 ml of DMF was stirred for 2 days at 60 °C. The reaction mixture was concentrated under reduced pressure and the residue was subjected to silica gel column chromatography to give 2.10 g of compound 18. 1 H-NMR(CDCl 3 ) :1.26(3H, t, J=7.1 Hz), 2.52(3H, s), 2.98(3H, d, J=5.1 Hz), 3.60(2H, q, J=7.1 Hz), 4.20(2H, dq, J=8.9 Hz, 6.4 Hz), 4.52(2H, s), 8.29(1H, s). Step 4 A solution of compound 18 (2.10 g) in 20 ml of 25% hydrobromic acid in acetic acid was reacted for 7 h at 70 °C. The solvent was removed under reduced pressure, and the residue was dissolved in 15 ml of DMF. The resulting mixture was added to a suspension of 2-(4-nitrophenyl)-5-mercapto-1,3,4-oxadiazole (1.69 g) and potassium carbonate (3.80 g) in 15 ml of DMF at ice-cooling. The reaction mixture was stirred for 1 h at room temperature and added water. The appeared precipitate was filtered, dried, and subjected to silica gel column chromatography and crystalized from methanol/dichloromethane/diethyl ether to give 3.24 g of compound C-1 . The physical data was shown in Table 6. Reference 2 Step 1 To a compound A-1 (4.00 g) were added DMF (200 ml) and propargylamine (7.66 g), and the mixture was stirred for 17 h at 65 °C. DMF was removed under reduced pressure and water and brine were added. The mixture was extracted with ethyl acetate, and the organic layer was dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography and crystalized from methanol/dichloromethane/diethyl ether to give 0.74 g of compound C-2. The physical data were shown in Table 6. Example No. Compound No. R 18 R X R 15 R 16 1 H-NMR(CDCl 3 ) (δ) ppm 10 A-10 NH 2 H SMe NHM e 2.55(3H, s), 2.56(3H, s), 3.08(3H, d, J = 5.3), 4.02(2H, br), 4.51(2H, s), 6.70(2H, J=8.9), d, 7.76(2H, d, J = 8.9), 8.49(1H, s), 11.13(1H, br) 11 A-11 NH 2 H SMe NHEt 1.34(3H, t, J = 7.3), 2.54(3H, s), 2.56(3H, s), 3.43(2H, dq, J = 7.3, 5.4), 3.50(2H, br), 4.02(2H, s), 6.71(2H, d, J = 8.7), 7.76(2H, d, J = 8.7), 8.49(1H, s), 11.30(1H, br) 12 A-12 NH 2 H SMe NHPr 1.06(3H, t, J = 7.3), 1.72(2H, sext, J = 7.3), 2.54(3H, s), 2.56(3H, s), 3.36(2H, q, J = 7.3), 4.02(2H, br), 4.51(2H, s), 6.71(2H, d, J = 8.7), 7.76(2H, d, J = 8.7), 8.49(1H, s) 13 A-13 NH 2 H SEt NHMe 1.41(3H, t, J = 7.3), 2.55(3H, s), 3.08(3H, J = 5.1), 3.21(2H, q, J = 7.3), 4.02(2H, br), 4.51(2H, s), 6.70(2H, d, J = 8.5), 7.76(2H, d, J = 8.5), 8.50(1H, s) 14 A-14 NH 2 H SEt NHEt 1.33(3H, t, J = 7.3), 1.39(3H, t, J = 7.3), 2.54(3H, s), 3.20(2H, q, J = 7.3), 3.43(2H, dq, J = 7.3, 5.4), 4.02(2H, br), 4.50(2H, s), 6.71(2H, d, J = 8.9), 7.77(2H, d, J = 8.9), 8.49(1H; s), 11.33(1H, br) 15 A-15 NH 2 H SPr NHMe 1.04(3H, t, J = 7.3), 1.78(2H, sext, J = 7.3), 2.54(3H, s), 3.08(3H, d, J = 5.3), 3.18(2H, t, J = 7.3), 4.03(2H, br), 4.49(2H, s), 6.70(2H, d, J = 8.9), 7.76(2H, d, J = 8.9), 8.49(1H, s), 11.20(1H, br) 16 A-16 NH 2 H SPr NHEt 1.04(3H, t, J = 7.3), 1.33(3H, t, J = 7.3), 1.78(2H, sext, J = 7.3), 2.54(3H, s), 3.18(2H, t, J = 7.3), 3.44(2H, dq, J = 7.3, 5.4), 4.01(2H, br), 4.49(2H, s), 6.71(2H, d, J = 8.9), 7.76(2H, d, J = 8.9), 8.49(1H, s), 11.35(1H, br) 17 A.17 Me H SMe NHPr 1.06(3H, t, J = 7.3), 1.72(2H, sext, J = 7.3), 2.41(3H, s), 2.54(3H, s), 2.56(3H, s), 3.37(2H, dt, J = 5.4, 7.3), 4.54(2H, s), 7.28(2H, d, J = 8.2), 7.86(2H, d, J = 8.2), 8.51(1H, s) 18 A-18 NO 2 H NHNMe 2 NHPr 1.00(3H, t, J = 7.3), 1.67(2H, sext, J = 7.3), 2.51(3H, s), 2.64(6H, s), 3.44(2H, q, J = 7.3), 4.52(2H, s), 6.39(1H, br), 8.18(2H, d, J = 9.0), 8.34(1H, s), 8.36(2H, d, J = 9.0) Example No. Compound No. R 18 R x R 15 R 16 1 H-NMR(CDCl 3 ) (δ) ppm 19 A-19 NO 2 H NHOMe NHMe 2.52(1.95H, s), 2.58(1.05H, s), 2.83(1.05H, d, J = 5.1), 3.05(1.95H, d, J = 5.1),3.75(1.05H, s), 3.81(1.95H, s), 4.49(0.7H, s), 4.53(1.3H, s), 5.62(0.65H, br), 7.77(0.35H, br), 8.16(2H, d, J = 8.5), 8.35(2H, d, J=8.5), 8.36(1H, s) 20 A-20 NO 2 H S(CH 2 ) 3 NH 2.13 - 2.25(2H, m), 2.53(3H, s), 3.08 - 3.13(2H, m), 3.55 - 3.65(2H, m), 4.50(2H, s), 8.16(2H, d, J = 8.9), 8.35(2H, d, J = 8.9), 8.49(1H, s), 11.85(1H, br) 21 A-21 NO 2 H S(CH 2 ) 2 NH 2.59(3H, s), 3.31(2H, t, J = 7.3), 3.92(2H, br), 4.53(2H, s), 8.16(2H, d, J = 8.9), 8.35(2H, d, J = 8.9), 8.55(1H, s) 22 A-22 NO 2 Me SMe NHEt 1.34(3H, t, J = 7.2), 1.95(3H, d, J = 7.2), 2.56(3H, s), 2.57(3H, s), 3.44(2H, dq, J = 5.4, 7.2), 5.49(1H, q, J = 7.2), 8.16(2H, d, J = 8.8), 8.35(2H, d, J = 8.8), 8.46(1H, s), 11.36(1H, br) 23- A-23 NO 2 Me NHEt NHEt 1.29(6H, t, J = 7.1), 1.95(3H, d, J = 7.1), 2.48(3H, s), 3.39(4H, br), 5.33(1H, q, J= 7.1), 8.17(2H, d, J = 9.0), 8.25(1H, s), 8.34(2H, d; J = 9.0) 24 A-24 NO 2 H OMe NHMe 2.56(3H, s), 2.99(3H, d, J = 5.1), 3.98(3H, s) 4.55(2H, s), 8.16(2H, d, J = 9.2), 8.41(2H, d, J = 9.2), 8.47(1H, s), 9.96(1H, br) 25 A-25 NO 2 H OEt NHMe 1.40(3H, t, J = 7.2), 2.55(3H, s), 2.98(3H, d,J = 4.9), 4.45(2H, q, J = 7,2), 4.53(2H, s), 8.16(2H, d, J = 9.0), 8.35(2H, d, J=9.0), 8.45(1H, s), 10.01(1H, br) 26 A-26 Me H OMe NHPr 1.02(3H, t, J = 7.3), 1.63(2H, tq, J = 6.8, 7.3), 2.41(3H, s), 2.54(3H, s), 3.31(2H, dt, J = 5.6, 6.8), 3.95(3H, s), 4.51(2H, s), 7.28(2H, d, J = 8.3), 7.86(2H, d, J = 8.3), 8.44(1H, s), 10.18(1H, br) 27 A-27 Me H OEt NHPr 1.02(3H, t, J = 7.3), 1.37(3H, t, J = 7.1), 1.64(2H, sext, J = 7.3), 2.41(3H, s), 2.54(3H, s), 3.32(2H, dt, J = 5.5, 7.3), 4.44(2H, q, J = 7. 1),4.49(2H, s), 7.28(2H, d, J = 8.4), 7.86(2H, d, J = 8.4), 8.43(1H, s) 33 A-28 Cl H SEt SEt 1.37(6H, t, J = 7.4), 2.67(3H, s), 3.16(4H, q, J = 7.4), 4.44(2H, s), 7.47(2H, d, J = 8.9), 7.92(2H, d, J = 8.9), 8.67(1H, s), Example No. Compound No. R 18 R x R 15 R 16 1 H-NMR(CDCl 3 ) (δ) ppm 34 A-29 NO 2 H SMe NHC H 2 CF 3 2.58(3H, s), 2.61(3H, s), 4.05(2H, dq, J= 6.4, 8.7), 4.60(2H, s), 8.16(2H, d, J = 8.9), 8.35(2H, d, J = 8.9), 8.63(1H, s), 12.03(1H, br). 35 A-30 NH 2 H SMe NHC H 2 CF 3 2.57(3H, s), 2.60(3H, s), 4.02(2H, br), 4.03(2H, dq, J= 6.5, 8.7), 4.53(2H, s), 6.71(2H, d, J = 8.8), 7.76(2H, d, J = 8.8), 8.59(1H, s), 12.02(1H, br). 36 A-31 NO 2 H SMe NHPh 2.54(3H, s), 2.59(3H, s), 4.64(2H, s), 7.34(1H, t, J = 7.6), 7.35(2H, d, J = 7.6), 7.44(2H, t, J = 7.6), 8.17(2H, d, J = 9.2), 8.36(2H, d, J = 9.2), 8.63(1H, s), 13.11(1H, br). 37 A-32 NO 2 H OMe NHET 1.26(3H, t, J = 7.3), 2.55(3H, s), 3.39(2H, dq, J= 5.6, 7.3), 3.97(3H, s), 4.55(2H, s), 8.16(2H, d, J = 9.0), 8.35(2H, d, J = 9.0), 8.46(1H, s), 10.09(1H, t-like, J = 5.6). 38 A-33 NO 2 H OEt NHEt 1.27(3H, t, J = 7.3), 1.39(3H, t, J = 7.1), 2.55(3H, s), 3.40(2H, dq, J= 5.6, 7.3), 4.45(2H, q, J = 7.1), 4.53(2H, s), 8.16(2H, d, J = 9.0), 8.35(2H, d, J = 9.0), 8.45(1H, s), 10.14(1H, t-like, J = 5.6). 39 A-34 NO 2 H OiPr NHMe 1.38(6H, d, J = 6.1), 2.55(3H, s), 2.96(3H, d, J= 4.9), 4.52(2H, s), 5.40(1H, sept, J = 6.1), 8.17(2H, d, J = 8.9), 8.35(2H, d, J = 8.9), 8.44(1H, s), 10.06(1H, br). 40 A-35 NO 2 H O i Pr NHEt 1.26(3H, t, J = 7.3), 1.37(6H, d, J = 6.3), 2.54(3H, s), 3.38(2H, dq, J= 5.4, 7.3), 4.52(2H, s), 5.40(1H, sept, J = 6.3), 8.17(2H, d, J = 9.0), 8.35(2H, d, J = 9.0), 8.44(1H, s), 10.19(1H, br). Compounds D-1 to D-1700 shown in Tablse 7 to Table 23 are able to synthesize in a manner similar to those described in Example 1 or Example 18, and were compounds E-1 to E-60 shown in Table 24 are able to synthesize in a manner similar to described in Example 20. Table 7 to Table 24 Compound No. R 15 R 16 R 17 R 18 Compound No. R 15 R 16 R 17 R 18 D-1 NH 2 SH H 4-NH 2 D-51 NH-allyl SH H 4-NH 2 D-2 NH 2 SMe H 4-NH 2 D-52 NH-allyl SMe H 4-NH 2 D-3 NH 2 SEt H 4-NH 2 D-53 NH-allyl SEt H 4-NH 2 D-4 NH 2 S-n-Pr H 4-NH 2 D-54 NH-allyl S-n-Pr H 4-NH 2 D-5 NH 2 S-i-Pr H 4-MH 2 D-55 NH-allyl S-i-Pr H 4-NH 2 D-6 NH 2 S-n-Bu H 4-NH 2 D-56 NH-allyl S-n-Bu H 4-NH 2 D-7 NH 2 S-allyl H 4-MH 2 D-57 NH-allyl S-allyl H 4-NH 2 D-8 NH 2 S-propargyl H 4-NH 2 D-58 NH-allyl S-propargyl H 4-NH 2 D-9 NH 2 SCH 2 CF 3 H 4-NH 2 D-59 NH-allyl SCH 2 CF 3 H 4-NH 2 D-10 NH 2 SCH 2 CH 2 F H 4-NH 2 D-60 NH-allyl SCH 2 CH 2 F H 4-NH 2 D-11 NHMe SH H 4-NH 2 D-61 NH-propargyl SH H 4-NH 2 D-12 NHMe SMe H 4-NH 2 D-62 NH-propargyl SMe H 4-NH 2 D-13 NHMe SEt H 4-NH 2 D-63 NH-propargyl SEt H 4-NH 2 D-14 NHMe S-n-Pr H 4-NH 2 D-64 NH-propargyl S-n-Pr H 4-NH 2 D-15 NHMe S-i-Pr H 4-NH 2 D-65 NH-propargyl S-i-Pr H 4-NH 2 D-16 NHMe S-n-Bu H 4-NH 2 D-66 NH-propargyl S-n-Bu H 4-NH 2 D-17 NHMe S-allyl H 4-NH 2 D-67 NH-propargyl S-allyl H 4-NH 2 D-18 NHMe S-propargyl H 4-NH 2 D-68 NH-propargyl S-propargyl H 4-NH 2 D-19 NHMe SCH 2 CF 3 H 4-NH 2 D-69 NH-propargyl SCH 2 CF 3 H 4-NH 2 D-20 NHMe SCH 2 CH 2 F H 4-NH 2 D-70 NH-propargyl SCH 2 CH 2 F H 4-NH 2 D-21 NHEt SH H 4-NH 2 D-71 NHCH 2 CF 3 SH H 4-NH 2 D-22 NHEt SMe H 4-NH 2 D-72 NHCH 2 CF 3 SMe H 4-NH 2 D-23 NHEt SEt H 4-NH 2 D-73 NHCH 2 CF 3 SEt H 4-NH 2 D-24 NHEt S-n-Pr H 4-NH 2 D-74 NHCH 2 CF 3 S-n-pr H 4-NH 2 D-25 NHEt S-i-Pr H 4-NH 2 D-75 NHCH 2 CF 3 S-i-Pr H 4-NH 2 D-26 NHEt S-n-Bu H 4-NH 2 D-76 NHCH 2 CF 3 S-n-Bu H 4-NH 2 D-27 NHEt S-allyl H 4-NH 2 D-77 NHCH 2 CF 3 S-allyl H 4-NH 2 D-28 NHEt S-propargyl H 4-NH 2 D-78 NHCH 2 CF 3 S-propargyl H 4-NH 2 D-29 NHEt SCH 2 CF 3 H 4-NH 2 D-79 NHCH 2 CF 3 SCH 2 CF 3 H 4-NH 2 D-30 NHEt SCH 2 CH 2 F H 4-NH 2 D-80 NHCH 2 CF 3 SCH 2 CH 2 F H 4-NH 2 D-31 NHPr SH H 4-NH 2 D-81 NHCH 2 CH 2 F SH H 4-NH 2 D-32 NHPr SMe H 4-NH 2 D-82 NHCH 2 CH 2 F SMe H 4-NH 2 D-33 NHPr SEt H 4-NH 2 D-83 NHCH 2 CH 2 F SEt H 4-NH 2 D-34 NHPr S-n-Pr H 4- NH 2 D-84 NHCH 2 CH 2 F S-n-Pr H 4-NH 2 D-35 NHPr S-i-Pr H 4-NH 2 D-85 NHCH 2 CH 2 F S-i-Pr H 4-NH 2 D-36 NHPr S-n-Bu H 4-NH 2 D-86 NHCH 2 CH 2 F S-n-Bu H 4-NH 2 D-37 NHPr S-allyl H 4-NH 2 D-87 NHCH 2 CH 2 F S-allyl H 4-NH 2 D-38 NHPr S-propargyl H 4-NH 2 D-88 NHCH 2 CH 2 F S-propargyl H 4-NH 2 D-39 NHPr SCH 2 CF 3 H 4-NH 2 D-89 NHCH 2 CH 2 F SCH 2 CF 3 H 4-NH 2 D-40 NHPr SCH 2 CH 2 F H 4-NH 2 D-90 NHCH 2 CH 2 F SCH 2 CH 2 F H 4-NH 2 D-41 NH-i-Pr SH H 4-NH 2 D-91 NH-n-Bu SH H 4-NH 2 D-42 NH-i-Pr SMe H 4-NH 2 D-92 NH-n-Bu SMe H 4-NH 2 D-43 NH-i-Pr SEt H 4-NH 2 D-93 NH-n-Bu SEt H 4-NH 2 D-44 NH-i-Pr S-n-Pr H 4-NH 2 D-94 NH-n-Bu S-n-Pr H 4-NH 2 D-45 NH-i-Pr S-i-Pr H 4-NH 2 D-95 NH-n-Bu S-i-Pr H 4-NH 2 D-46 NH-i-Pr S-n-Bu H 4-NH 2 D-96 NH-n-Bu S-n-Bu H 4-NH 2 D-47 NH-i-Pr S-allyl H 4-NH 2 D-97 NH-n-Bu S-allyl H 4-NH 2 D-48 NH-i-Pr S-propargyl H 4-NH 2 D-98 NH-n-Bu S-propargyl H 4-NH 2 D-49 NH-i-Pr SCH 2 CF 3 H 4-MH 2 D-99 NH-n-Bu SCH 2 CF 3 H 4-NH 2 D-50 NH-i-Pr SCH 2 CH 3 F H 4-NH 2 D-100 NH-n-Bu SCH 2 CH 2 F H 4-NH 2 Compound No. R 15 R 16 R 17 R 18 Compound No. R 15 R 16 R 17 R 18 D-101 NH2 SH H 2-NH 2 D-151 NH-allyl SH H 2-NH 2 D-102 NH 2 SMe H 2-NH 2 D-152 NH-allyl SMe H 2-NH 2 D-103 NH 2 SEt H 2-NH 2 D-153 NH-allyl SEt H 2-NH 2 D-104 NH 2 S-n-Pr H 2-NH 2 D-154 NH-allyl S-n-Pr H 2-NH 2 D-105 NH 2 S-i-Pr H 2-NH 2 D-155 NH-allyl S-i-Pr H 2-NH 2 D-106 NH 2 S-n-Bu H 2-NH 2 D-156 NH-allyl S-n-Bu H 2-NH 2 D-107 NH 2 S-allyl H 2-NH 2 D-157 NH-allyl S-allyl H 2-NH 2 D-108 NH 2 S-propargyl H 2-NH 2 D-158 NH-allyl S-propargyl H 2-NH 2 D-109 NH 2 SCH 2 CF 3 H 2-NH 2 D-159 NH-allyl SCH 2 CF 3 H 2-NH 2 D-110 NH 2 SCH 2 CH 2 F H 2-NH 2 D-160 NH-allyl SCH 2 CH 2 F H 2-NH 2 D-111 NHMe SH H 2-NH 2 D-161 NH-propargyl SH H 2-NH 2 D-112 NHMe SMe H 2-NH 2 D-162 NH-propargyl SMe H 2-NH 2 D-113 NHMe SEt H 2-NH 2 D-163 NH-propargyl SEt H 2-NH 2 D-114 NHMe S-n-Pr H 2-NH 2 D-164 NH-propargyl S-n-Pr H 2-NH 2 D-115 NHMe S-i-Pr H 2-NH 2 D-165 NH-propargyl S-i-Pr H 2-NH 2 D-116 NHMe S-n-Bu H 2-NH 2 D-166 NH-propargyl S-n-Bu H 2-NH 2 D-117 NHMe S-allyl H 2-NH 2 D-167 NH-propargyl S-allyl H 2-NH 2 D-118 NHMe S-propargyl H 2-NH 2 D-168 MH-propargyl S-propargyl H 2-NH 2 D-119 NHMe SCH 2 CF 3 H 2-NH 2 D-169 NH-propargyl SCH 2 CF 3 H 2-NH 2 D-120 NHMe SCH 2 CH 2 F H 2-NH 2 D-170 NH-propargyl SCH 2 CH 2 F H 2-NH 2 D-121 NHEt SH H 2-NH 2 D-171 NHCH 2 CF 3 SH H 2-NH 2 D-122 NHEt SMe H 2-NH 2 D-172 NHCH 2 CF 3 SMe H 2-NH 2 D-123 NHEt SEt H 2-NH 2 D-173 NHCH 2 CF 3 SEt H 2-NH 2 D-124 NHEt S-n-Pr H 2-NH 2 D-174 NHCH 2 CF 3 S-n-Pr H 2-NH 2 D-125 NHEt S-i-Pr H 2-NH 2 D-175 NHCH 2 CF 3 S-i-Pr H 2-NH 2 D-126 NHEt S-n-Bu H 2-NH 2 D-176 NHCH 2 CF 3 S-n-Bu H 2-NH 2 D-127 NHEt S-allyl H 2-NH 2 D-177 NHCH 2 CF 3 S-allyl H 2-NH 2 D-128 NHEt S-propargyl H 2-NH 2 D-178 NHCH 2 CF 3 S-propargyl H 2-NH 2 D-129 NHEt SCH 2 CF 3 H 2-NH 2 D-179 NHCH 2 CF 3 SCH 2 CF 3 H 2-NH 2 D-130 NHEt SCH 2 CH 2 F H 2-NH 2 D-180 NHCH 2 CF 3 SCH 2 CH 2 F H 2-NH 2 D-131 NHPr SH H 2-NH 2 D-181 NHCH 2 CH 2 F SH H 2-NH 2 D-132 NHPr SMe H 2-NH 2 D-182 NHCH 2 CH 2 F SMe H 2-NH 2 D-133 NHPr SEt H 2-NH 2 D-183 NHCH 2 CH 2 F SEt H 2-NH 2 D-134 NHPr S-n-Pr H 2-NH 2 D-184 NHCH 2 CH 2 F S-n-Pr H 2-NH 2 D-135 NHPr S-i-Pr H 2-NH 2 D-185 MHCH 2 CH 2 F S-i-Pr H 2-NH 2 D-136 NHPr S-n-Bu H 2-NH 2 D-186 NHCH 2 CH 2 F S-n-Bu H 2-NH 2 D-137 NHPr S-allyl H 2-NH 2 D-187 NHCH 2 CH 2 F S-allyl H 2-NH 2 D-138 NHPr S-propargyl H 2-NH 2 D-188 NHCH 2 CH 2 F S-propargyl H 2-NH 2 D-139 NHPr SCH 2 CF 3 H 2-NH 2 D-189 NHCH 2 CH 2 F SCH 2 CF 3 H 2-NH 2 D-140 NHPr SCH 2 CH 2 F H 2-NH 2 D-190 NHCH 2 CH 2 F SCH 2 CH 2 F H 2-NH 2 D-141 NH-i-Pr SH H 2-NH 2 D-191 NH-n-Bu SH H 2-NH 2 D-142 NH-i-Pr SMe H 2-NH 2 D-192 NH-n-Bu SMe H 2-NH 2 D-143 NH-i-Pr SEt H 2-NH 2 D-193 NH-n-Bu SEt H 2-NH 2 D-144 NH-i-Pr S-n-Pr H 2-NH 2 D-194 NH-n-Bu S-n-Pr H 2-NH 2 D-145 NH-i-Pr S-i-Pr H 2-NH 2 D-195 NH-n-Bu S-i-Pr H 2-NH 2 D-146 NH-i-Pr S-n-Bu H 2-NH 2 D-196 NH-n-Bu S-n-Bu H 2-NH 2 D-147 NH-i-Pr S-allyl H 2-NH 2 D-197 NH-n-Bu S-allyl H 2-NH 2 D-148 NH-i-Pr S-propargyl H 2-NH 2 D-198 NH-n-Bu S-propargyl H 2-NH 2 D-149 NH-i-Pr SCH 2 CF 3 H 2-NH 2 D-199 NH-n-Bu SCH 2 CF 3 H 2-NH 2 D-150 NH-i-Pr SCH 2 CH 2 F H 2-NH 2 D-200 NH-n-Bu SCH 2 CH 2 F H 2-NH 2 Compound No. R 15 R 16 R 17 R 18 Compound No. R 15 R 16 R 17 R 18 D-201 NH 2 SH H 4-Cl D-251 NH-allyl SH H 4-Cl D-202 NH 2 SMe H 4-Cl D-252 NH-allyl SMe H 4-Cl D-203 NH 2 SEt H 4-Cl D-253 NH-allyl SEt H 4-Cl D-204 NH 2 S-n-Pr H 4-Cl D-254 NH-allyl S-n-Pr H 4-Cl D-205 NH 2 S-i-Pr H 4-Cl D-255 NH-allyl S-i-Pr H 4-Cl D-206 NH 2 S-n-Bu H 4-Cl D-256 NH-allyl S-n-Bu H 4-Cl D-207 NH 2 S-allyl H 4-Cl D-257 NH-allyl S-allyl H 4-Cl D-208 NH 2 S-propargyl H 4-Cl D-258 NH-allyl S-propargyl H 4-Cl D-209 NH 2 SCH 2 CF 3 H 4-Cl D-259 NH-allyl SCH 2 CF 3 H 4-Cl D-210 NH 2 SCH 2 CH 2 F H 4-Cl D-260 NH-allyl SCH 2 CH 2 F H 4-Cl D-211 NHMe SH H 4-Cl D-261 NH-propargyl SH H 4-Cl D-212 NHMe SMe H 4-Cl D-262 NH-propargyl SMe H 4-Cl D-213 NHMe SEt H 4-Cl D-263 NH-propargyl SEt H 4-Cl D-214 NHMe S-n-Pr H 4-Cl D-264 NH-propargyl S-n-Pr H 4-Cl D-215 NHMe S-i-Pr H 4-Cl D-265 NH-propargyl S-i-Pr H 4-Cl D-216 NHMe S-n-Bu H 4-Cl D-266 NH-propargyl S-n-Bu H 4-Cl D-217 NHMe S-allyl H 4-Cl D-267 NH-propargyl S-allyl H 4-Cl D-218 NHMe S-propargyl H 4-Cl D-268 NH-propargyl S-propargyl H 4-Cl D-219 NHMe SCH 2 CF 3 H 4-Cl D-269 NH-propargyl SCH 2 CF 3 H 4-Cl D-220 NHMe SCH 2 CH 2 F H 4-Cl D-270 NH-propargyl SCH 2 CH 2 F H 4-Cl D-221 NHEt SH H 4-F D-271 NHCH 2 CF 3 SH H 4-Cl D-222 NHEt SMe H 4-Cl D-272 NHCH 2 CF 3 SMe H 4-Cl D-223 NHEt SEt H 4-Cl D-273 NHCH 2 CF 3 SEt H 4-Cl D-224 NHEt S-n-Pr H 4-Cl D-274 NHCH 2 CF 3 S-n-Pr H 4-Cl D-225 NHEt S-i-Pr H 4-Cl D-275 NHCH 2 CF 3 S-i-Pr H 4-Cl D-226 NHEt S-n-Bu H 4-Cl D-276 NHCH 2 CF 3 S-n-Bu H 4-Cl D-227 NHEt S-allyl H 4-Cl D-277 NHCH 2 CF 3 S-allyl H 4-Cl D-228 NHEt S-propargyl H 4-Cl D-278 NHCH 2 CF 3 S-propargyl H 4-Cl D-229 NHEt SCH 2 CF 3 H 4-Cl D-279 NHCH 2 CF 3 SCH 2 CF 3 H 4-Cl D-230 NHEt SCH 2 CH 2 F H 4-Cl D-280 NHCH 2 CF 3 SCH 2 CH 2 F H 4-Cl D-231 NHPr SH H 4-Cl D-281 NHCH 2 CH 2 F SH H 4-Cl D-232 NHPr SMe H 4-Cl D-282 NHCH 2 CH 2 F SMe H 4-Cl D-233 NHPr SEt H 4-Cl D-283 NHCH 2 CH 2 F SEt H 4-Cl D-234 NHPr S-n-Pr H 4-Cl D-284 NHCH 2 CH 2 F S-n-Pr H 4-Cl D-235 NHPr S-i-Pr H 4-Cl D-285 NHCH 2 CH 2 F S-i-Pr H 4-Cl D-236 NHPr S-n-Bu H 4-Cl D-286 NHCH 2 CH 2 F S-n-Bu H 4-Cl D-237 NHPr S-allyl H 4-Cl D-287 NHCH 2 CH 2 F S-allyl H 4-Cl D-238 NHPr S-propargyl H 4-Cl D-288 NHCH 2 CH 2 F S-propargyl H 4-Cl D-239 NHPr SCH 2 CF 3 H 4-Cl D-289 NHCH 2 CH 2 F SCH 2 CF 3 H 4-Cl D-240 NHPr SCH 2 CH 2 F H 4-Cl D-290 NHCH 2 CH 2 F SCH 2 CH 2 F H 4-Cl D-241 NH-i-Pr SH H 4-Cl D-291 NH-n-Bu SH H 4-Cl D-242 NH-i-Pr SMe H 4-Cl D-292 NH-n-Bu SMe H 4-Cl D-243 NH-i-Pr SEt H 4-Cl D-293 NH-n-Bu SEt H 4-Cl D-244 NH-i-Pr S-n-Pr H 4-Cl D-294 NH-n-Bu S-n-Pr H 4-Cl D-245 NH-i-Pr S-i-Pr H 4-Cl D-295 NH-n-Bu S-i-Pr H 4-Cl D-246 NH-i-Pr S-n-Bu H 4-Cl D-296 NH-n-Bu S-n-Bu H 4-Cl D-247 NH-i-Pr S-allyl H 4-Cl D-297 NH-n-Bu S-allyl H 4-Cl D-248 NH-i-Pr S-propargyl H 4-Cl D-298 NH-n-Bu S-propargyl H 4-Cl D-249 NH-i-Pr SCH 2 CF 3 H 4-Cl D-299 NH-n-Bu SCH 2 CF 3 H 4-Cl D-250 NH-i-Pr SCH 2 CH 2 F H 4-Cl D-300 NH-n-Bu SCH 2 CH 2 F H 4-Cl Compound No. R 15 R 16 R 17 R 18 Compound No. R 15 R 16 R 17 R 18 D-301 NH 2 SH H 4-Me D-351 NH-allyl SH H 4-Me D-302 NH 2 SMe H 4-Me D-352 NH-allyl SMe H 4-Me D-303 NH 2 SEt H 4-Me D-353 NH-allyl SEt H 4-Me D-304 NH 2 S-n-Pr H 4-Me D-354 NH-allyl S-n-Pr H 4-Me D-305 NH 2 S-i-Pr H 4-Me D-355 NH-allyl S-i-Pr H 4-Me D-306 NH 2 S-n-Bu H 4-Me D-356 NH-allyl S-n-Bu H 4-Me D-307 NH 2 S-allyl H 4-Me D-357 NH-allyl S-allyl H 4-Me D-308 NH 2 S-propargyl H 4-Me D-358 NH-allyl S-propargyl H 4-Me D-309 NH 2 SCH 2 CF 3 H 4-Me D-359 NH-allyl SCH 2 CF 3 H 4-Me D-310 NH 2 SCH 2 CH 2 F H 4-Me D-360 NH-allyl SCH 2 CH 2 F H 4-Me D-311 NHMe SH H 4-Me D-361 NH-propargyl SH H 4-Me D-312 NHMe SMe H 4-Me D-362 NH-propargyl SMe H 4-Me D-313 NHMe SEt H 4-Me D-363 NH-propargyl SEt H 4-Me D-314 NHMe S-n-Pr H 4-Me D-364 NH-propargyl S-n-Pr H 4-Me D-315 NHMe S-i-Pr H 4-Me D-365 NH-propargyl S-i-Pr H 4-Me D-316 NHMe S-n-Bu H 4-Me D-366 NH-propargyl S-n-Bu H 4-Me D-317 NHMe S-allyl H 4-Me D-367 NH-propargyl S-allyl H 4-Me D-318 NHMe S-propargyl H 4-Me D-368 NH-propargyl S-propargyl H 4-Me D-319 NHMe SCH 2 CF 3 H 4-Me D-369 NH-propargyl SCH 2 CF 3 H 4-Me D-320 NHMe SCH 2 CH 2 F H 4-Me D-370 NH-propargyl SCH 2 CH 2 F H 4-Me D-321 NHEt SH H 4-Me D-371 NHCH 2 CF 3 SH H 4-Me D-322 NHEt SMe H 4-Me D-372 NHCH 2 CF 3 SMe H 4-Me D-323 NHEt SEt H 4-Me D-373 NHCH 2 CF 3 SEt H 4-Me D-324 NHEt S-n-Pr H 4-Me D-374 NHCH 2 CF 3 S-n-Pr H 4-Me D-325 NHEt S-i-Pr H 4-Me D-375 NHCH 2 CF 3 S-i-Pr H 4-Me D-326 NHEt S-n-Bu H 4-Me D-376 NHCH 2 CF 3 S-n-Bu H 4-Me D-327 NHEt S-allyl H 4-Me D-377 NHCH 2 CF 3 S-allyl H 4-Me D-328 NHEt S-propargyl H 4-Me D-378 NHCH 2 CF 3 S-propargyl H 4-Me D-329 NHEt SCH 2 CF 3 H 4-Me D-379 NHCH 2 CF 3 SCH 2 CF 3 H 4-Me D-330 NHEt SCH 2 CH 2 F H 4-Me D-380 NHCH 2 CF 3 SCH 2 CH 2 F H 4-Me D-331 NHPr SH H 4-Me D-381 NHCH 2 CH 2 F SH H 4-Me D-332 NHPr SMe H 4-Me D-382 NHCH 2 CH 2 F SMe H 4-Me D-333 NHPr SEt H 4-Me D-383 NHCH 2 CH 2 F SEt H 4-Me D-334 NHPr . S-n-Pr H 4-Me D-384 NHCH 2 CH 2 F S-n-Pr H 4-Me D-335 NHPr S-i-Pr H 4-Me D-385 NHCH 2 CH 2 F S-i-Pr H 4-Me D-336 NHPr S-n-Bu H 4-Me D-386 NHCH 2 CH 2 F S-n-Bu H 4-Me D-337 NHPr S-allyl H 4-Me D-387 NHCH 2 CH 2 F S-allyl H 4-Me D-338 NHPr S-propargyl H 4-Me D-388 NHCH 2 CH 2 F S-propargyl H 4-Me D-339 NHPr SCH 2 CF 3 H 4-Me D-389 NHCH 2 CH 2 F SCH 2 CF 3 H 4-Me D-340 NHPr SCH 2 CH 2 F H 4-Me D-390 NHCH 2 CH 2 F SCH 2 CH 2 F H 4-Me D-341 NH-i-Pr SH H 4-Me D-391 NH-n-Bu SH H 4-Me D-342 NH-i-Pr SMe H 4-Me D-392 NH-n-Bu SMe H 4-Me D-343 NH-i-Pr SEt H 4-Me D-393 NH-n-Bu SEt H 4-Me D-344 NH-i-Pr S-n-Pr H 4-Me D-394 NH-n-Bu S-n-Pr H 4-Me D-345 NH-i-Pr S-i-Pr H 4-Me D-395 NH-n-Bu S-i-Pr H 4-Me D-346 NH-i-Pr S-n-Bu H 4-Me D-396 NH-n-Bu S-n-Bu H 4-Me D-347 NH-i-Pr S-allyl H 4-Me D-397 NH-n-Bu S-allyl H 4-Me D-348 NH-i-Pr S-propargyl H 4-Me D-398 NH-n-Bu S-propargyl H 4-Me D-349 NH-i-Pr SCH 2 CF 3 H 4-Me D-399 NH-n-Bu SCH 2 CF 3 H 4-Me D-350 NH-i-Pr SCH 2 CH 2 F H 4-Me D-400 NH-n-Bu SCH 2 CH 2 F H 4-Me Compound No. R 15 R 16 R 17 R 18 Compound No. R 15 R 16 R 17 R 18 D-401 NH 2 SH Me 2-NH 2 D-451 NH-allyl SH Me 2-NH 2 D-402 NH 2 SMe Me 2-NH 2 D-452 NH-allyl SMe Me 2-NH 2 D-403 NH 2 SEt Me 2-NH 2 D-453 NH-allyl SEt Me 2-NH 2 D-404 NH 2 S-n-Pr Me 2-NH 2 D-454 NH-allyl S-n-Pr Me 2-NH 2 D-405 NH 2 S-i-Pr Me 2-NH 2 D-455 NH-allyl S-i-Pr Me 2-NH 2 D-406 NH 2 S-n-Bu Me 2-NH 2 D-456 NH-allyl S-n-Bu Me 2-NH 2 D-407 NH 2 S-allyl Me 2-NH 2 D-457 NH-allyl S-allyl Me 2-NH 2 D-408 NH 2 S-propargyl Me 2-NH 2 D-458 NH-allyl S-Propargyl Me 2-NH 2 D-409 NH 2 SCH 2 CF 3 Me 2-NH 2 D-459 NH-allyl SCH 2 CF 3 Me 2-NH 2 D-410 NH 2 SCH 2 CH 2 F Me 2-NH 2 D-460 NH-allyl SCH 2 CH 2 F Me 2-NH 2 D-411 NHMe SH Me 2-NH 2 D-461 NH-propargyl SH Me 2-NH 2 D-412 NHMe SMe Me 2-NH 2 D-462 NH-propargyl SMe Me 2-NH 2 D-413 NHMe SEt Me 2-NH 2 D-463 NH-propargyl SEt Me 2-NH 2 D-414 NHMe S-n-Pr Me 2-NH 2 D-464 NH-propargyl S-n-Pr Me 2-NH 2 D-415 NHMe S-i-Pr Me 2-NH 2 D-465 NH-propargyl S-i-Pr Me 2-NH 2 D-416 NHMe S-n-Bu Me 2-NH 2 D-466 NH-propargyl S-n-Bu Me 2-NH 2 D-417 NHMe S-allyl Me 2-NH 2 D-467 NH-propargyl S-allyl Me 2-NH 2 D-418 NHMe S-propargyl Me 2-NH 2 D-468 NH-propargyl S-propargyl Me 2-NH 2 D-419 NHMe SCH 2 CF 3 Me 2-NH 2 D-469 NH-propargyl SCH 2 CF 3 Me 2-NH 2 D-420 NHMe SCH 2 CH 2 F Me 2-NH 2 D-470 NH-propargyl SCH 2 CH 2 F Me 2-NH 2 D-421 NHEt SH Me 2-NH 2 D-471 NHCH 2 CF 3 SH Me 2-NH 2 D-422 NHEt SMe Me 2-NH 2 D-472 NHCH 2 CF 3 SMe Me 2-NH 2 D-423 NHEt SEt Me 2-NH 2 D-473 NHCH 2 CF 3 SEt Me 2-NH 2 D-424 NHEt S-n-Pr Me 2-NH 2 D-474 NHCH 2 CF 3 S-n-Pr Me 2-NH 2 D-425 NHEt S-i-Pr Me 2-NH 2 D-475 NHCH 2 CF 3 S-i-Pr Me 2-NH 2 D-426 NHEt S-n-Bu Me 2-NH 2 D-476 NHCH 2 CF 3 S-n-Bu Me 2-NH 2 D-427 NHEt S-allyl Me 2-NH 2 D-477 NHCH 2 CF 3 S-allyl Me 2-NH 2 D-428 NHEt S-propargyl Me 2-NH 2 D-478 NHCH 2 CF 3 S-propargyl Me 2-NH 2 D-429 NHEt SCH 2 CF 3 Me 2-NH 2 D-479 NHCH 2 CF 3 SCH 2 CF 3 Me 2-NH 2 D-430 NHEt SCH 2 CH 2 F Me 2-NH 2 D-480 NHCH 2 CF 3 SCH 2 CH 2 F Me 2-NH 2 D-431 NHPr SH Me 2-NH 2 D-481 NHCH 2 CH 2 F SH Me 2-NH 2 D-432 NHPr SMe Me 2-NH 2 D-482 NHCH 2 CH 2 F SMe Me 2-NH 2 D-433 NHPr SEt Me 2-NH 2 D-483 NHCH 2 CH 2 F SEt Me 2-NH 2 D-434 NHPr S-n-Pr Me 2-NH 2 D-484 NHCH 2 CH 2 F S-n-Pr Me 2-NH 2 D-435 NHPr S-i-Pr Me 2-NH 2 D-485 NHCH 2 CH 2 F S-i-Pr Me 2-NH 2 D-436 NHPr S-n-Bu Me 2-NH 2 D-486 NHCH 2 CH 2 F S-n-Bu Me 2-NH 2 D-437 NHPr S-allyl Me 2-NH 2 D-487 NHCH 2 CH 2 F S-allyl Me 2-NH 2 D-438 NHPr S-propargyl Me 2-NH 2 D-488 NHCH 2 CH 2 F S-propargyl Me 2-NH 2 D-439 NHPr SCH 2 CF 3 Me 2-NH 2 D-489 NHCH 2 CH 2 F SCH 2 CF 3 Me 2-NH 2 D-440 NHPr SCH 2 CH 2 F Me 2-NH 2 D-490 NHCH 2 CH 2 F SCH 2 CH 2 F Me 2-NH 2 D-441 NH-i-Pr SH Me 2-NH 2 D-491 NH-n-Bu SH Me 2-NH 2 D-442 NH-i-Pr SMe Me 2-NH 2 D-492 NH-n-Bu SMe Me 2-NH 2 D-443 NH-i-Pr SEt Me 2-NH 2 D-493 NH-n-Bu SEt Me 2-NH 2 D-444 NH-i-Pr S-n-Pr Me 2-NH 2 D-494 NH-n-Bu S-n-Pr Me 2-NH 2 D-445 NH-i-Pr S-i-Pr Me 2-NH 2 D-495 NH-n-Bu S-i-Pr Me 2-NH 2 D-446 NH-i-Pr S-n-Bu Me 2-NH 2 D-496 NH-n-Bu S-n-Bu Me 2-NH 2 D-447 NH-i-Pr S-allyl Me 2-NH 2 D-497 NH-n-Bu S-allyl Me 2-NH 2 D-448 NH-i-Pr S-propargyl Me 2-NH 2 D-498 NH-n-Bu S-propargyl Me 2-NH 2 D-449 NH-i-Pr SCH 2 CF 3 Me 2-NH 2 D-499 NH-n-Bu SCH 2 CF 3 Me 2-NH 2 D-450 NH-i-Pr SCH 2 CH 2 F Me 2-NH 2 D-500 NH-n-Bu SCH 2 CH 2 F Me 2-NH 2 Compound No. R 15 R 16 R 17 R 18 Compound No. R 15 R 16 R 17 R 18 D-501 NH 2 SH Et 4-NO 2 D-551 NH-allyl SH Et 4-NO 2 D-502 NH 2 SMe Et 4-NO 2 D-552 NH-allyl SMe Et 4-NO 2 D-503 NH 2 SEt Et 4-NO 2 D-553 NH-allyl SEt Et 4-NO 2 D-504 NH 2 S-n-Pr Et 4-NO 2 D-554 NH-allyl S-n-Pr Et 4-NO 2 D-505 NH 2 S-i-Pr Et 4-NO 2 D-555 NH-allyl S-i-Pr Et 4-NO 2 D-506 NH 2 S-n-Bu Et 4-NO 2 D-556 NH-allyl S-n-Bu Et 4-NO 2 D-507 NH 2 S-allyl Et 4-NO 2 D-557 NH-allyl S-allyl Et 4-NO 2 D-508 NH 2 S-propargyl Et 4-NO 2 D-558 NH-allyl S-propargyl Et 4-NO 2 D-509 NH 2 SCH 2 CF 3 Et 4-NO 2 D-559 NH-allyl SCH 2 CF 3 Et 4-NO 2 D-510 NH 2 SCH 2 CH 2 F Et 4-NO 2 D-560 NH-allyl SCH 2 CH 2 F Et 4-NO 2 D-511 NHMe SH Et 4-NO 2 D-561 NH-propargyl SH Et 4-NO 2 D-512 NHMe SMe Et 4-NO 2 D-562 NH-propargyl SMe Et 4-NO 2 D-513 NHMe SEt Et 4-NO 2 D-563 NH-propargyl SEt Et 4-NO 2 D-514 NHMe S-n-Pr Et 4-NO 2 D-564 NH-propargyl S-n-Pr Et 4-NO 2 D-515 NHMe S-i-Pr Et 4-NO 2 D-565 NH-propargyl S-i-Pr Et 4-NO 2 D-516 NHMe S-n-Bu Et 4-NO 2 D-566 NH-propargyl S-n-Bu Et 4-NO 2 D-517 NHMe S-allyl Et 4-NO 2 D-567 NH-propargyl S-allyl Et 4-NO 2 D-518 NHMe S-propargyl Et 4-NO 2 D-568 NH-propargyl S-propargyl Et 4-NO 2 D-519 NHMe SCH 2 CF 3 Et 4-NO 2 D-569 NH-propargyl SCH 2 CF 3 Et 4-NO 2 D-520 NHMe SCH 2 CH 2 F Et 4-NO 2 D-570 NH-propargyl SCH 2 CH 2 F Et 4-NO 2 D-521 NHEt SH Et 4-NO 2 D-571 NHCH 2 CF 3 SH Et 4-NO 2 D-522 NHEt SMe Et 4-NO 2 D-572 NHCH 2 CF 3 SMe Et 4-NO 2 D-523 NHEt SEt Et 4-NO 2 D-573 NHCH 2 CF 3 SEt Et 4-NO 2 D-524 NHEt S-n-Pr Et 4-NO 2 D-574 NHCH 2 CF 3 S-n-Pr Et 4-NO 2 D-525 NHEt S-i-Pr Et 4-NO 2 D-575 NHCH 2 CF 3 S-i-Pr Et 4-NO 2 D-526 NHEt S-n-Bu Et 4-NO 2 D-576 NHCH 2 CF 3 S-n-Bu Et 4-NO 2 D-527 NHEt S-allyl Et 4-NO 2 D-577 NHCH 2 CF 3 S-allyl Et 4-NO 2 D-528 NHEt S-propargyl Et 4-NO 2 D-578 NHCH 2 CF 3 S-propargyl Et 4-NO 2 D-529 NHEt SCH 2 CF 3 Et 4-NO 2 D-579 NHCH 2 CF 3 SCH 2 CF 3 Et 4-NO 2 D-530 NHEt SCH 2 CH 2 F Et 4-NO 2 D-580 NHCH 2 CF 3 SCH 2 CH 2 F Et 4-NO 2 D-531 NHPr SH Et 4-NO 2 D-581 NHCH 2 CH 2 F SH Et 4-NO 2 D-532 NHPr SMe Et 4-NO 2 D-582 NHCH 2 CH 2 F SMe Et 4-NO 2 D-533 NHPr SEt Et 4-NO 2 D-583 NHCH 2 CH 2 F SEt Et 4-NO 2 D-534 NHPr S-n-Pr Et 4-NO 2 D-584 NHCH 2 CH 2 F S-n-Pr Et 4-NO 2 D-535 NHPr S-i-Pr Et 4-NO 2 D-585 NHCH 2 CH 2 F S-i-Pr Et 4-NO 2 D-536 NHPr S-n-Bu Et 4-NO 2 D-586 NHCH 2 CH 2 F S-n-Bu Et 4-NO 2 D-537 NHPr S-allyl Et 4-NO 2 D-587 NHCH 2 CH 2 F S-allyl Et 4-NO 2 D-538 NHPr S-propargyl Et 4-NO 2 D-588 NHCH 2 CH 2 F S-propargyl Et 4-NO 2 D-539 NHPr SCH 2 CF 3 Et 4-NO 2 D-589 NHCH 2 CH 2 F SCH 2 CF 3 Et 4-NO 2 D-540 NHPr SCH 2 CH 2 F Et 4-NO 2 D-590 NHCH 2 CH 2 F SCH 2 CH 2 F Et 4-NO 2 D-541 NH-i-Pr SH Et 4-NO 2 D-591 NH-n-Bu SH Et 4-NO 2 D-542 NH-i-Pr SMe Et 4-NO 2 D-592 NH-n-Bu SMe Et 4-NO 2 D-543 NH-i-Pr SEt Et 4-NO 2 D-593 NH-n-Bu SEt Et 4-NO 2 D-544 NH-i-Pr S-n-Pr Et 4-NO 2 D-594 NH-n-Bu S-n-Pr Et 4-NO 2 D-545 NH-i-Pr S-i-Pr Et 4-NO 2 D-595 NH-n-Bu S-i-Pr Et 4-NO 2 D-546 NH-i-Pr S-n-Bu Et 4-NO 2 D-596 NH-n-Bu S-n-Bu Et 4-NO 2 D-547 NH-i-Pr S-allyl Et 4-NO 2 D-597 NH-n-Bu S-allyl Et 4-NO 2 D-548 NH-i-Pr S-propargyl Et 4-NO 2 D-598 NH-n-Bu S-propargyl Et 4-NO 2 D-549 NH-i-Pr SCH 2 CF 3 Et 4-NO 2 D-599 NH-n-Bu SCH 2 CF 3 Et 4-NO 2 D-550 NH-i-Pr SCH 2 CH 2 F Et 4-NO 2 D-600 NH-n-Bu SCH 2 CH 2 F Et 4-NO 2 Compound No. R 15 R 16 R 17 R 18 Compound No. R 15 R 16 R 17 R 18 D-601 NH 2 SH Et 4-NH 2 D-651 NH-allyl SH Et 4-NH 2 D-602 NH 2 SMe Et 4-NH 2 D-652 NH-allyl SMe Et 4-NH 2 D-603 NH 2 SEt Et 4-NH 2 D-653 NH-allyl SEt Et 4-NH 2 D-604 NH 2 S-n-Pr Et. 4-NH 2 D-654 NH-allyl S-n-Pr Et 4-NH 2 D-605 NH 2 S-i-Pr Et 4-NH 2 D-655 NH-allyl S-i-Pr Et 4-NH 2 D-606 NH 2 S-n-Bu Et 4-NH 2 D-656 NH-allyl S-n-Bu Et 4-NH 2 D-607 NH 2 S-allyl Et 4-NH 2 D-657 NH-allyl S-allyl Et 4-NH 2 D-608 NH 2 S-propargyl Et 4-NH 2 D-658 NH-allyl S-propargyl Et 4-NH 2 D-609 NH 2 SCH 2 CF 3 Et 4-NH 2 D-659 NH-allyl SCH 2 CF 3 Et 4-NH 2 D-610 NH 2 SCH 2 CH 2 F Et 4-NH 2 D-660 NH-allyl SCH 2 CH 2 F Et 4-NH 2 D-611 NHMe SH Et 4-NH 2 D-661 NH-propargvl SH Et 4-NH 2 D-612 NHMe SMe Et 4-NH 2 D-662 NH-propargyl SMe Et 4-NH 2 D-618 NHMe SEt Et 4-NH 2 D-663 NH-propargyl SEt Et 4-NH 2 D-614 NHMe S-n-Pr Et 4-NH 2 D-664 NH-propargyl S-n-Pr Et 4-NH 2 D-615 NHMe S-i-Pr Et 4-NH 2 D-665 NH-proPargyl S-i-Pr Et 4-NH 2 D-616 NHMe S-n-Bu Et 4-NH 2 D-666 NH-propargyl S-n-Bu Et 4-NH 2 D-617 NHMe S-allyl Et 4-NH 2 D-667 NH-proparagyl S-allyl Et 4-NH 2 D-618 NHMe S-propargyl Et 4-NH 2 D-668 NH-propargyl S-propargyl Et 4-NH 2 D-619 NHMe SCH 2 CF 3 Et 4-NH 2 D-669 NH-propargyl SCH 2 CF 3 Et 4-NH 2 D-620 NHMe SCH 2 CH 2 F Et 4-NH 2 D-670 NH-propargyl SCH 2 CH 2 F Et 4-NH 2 D-621 NHEt SH Et 4-NH 2 D-671 NHCH 2 CF 3 SH Et 4-NH 2 D-622 NHEt SMe Et 4-NH 2 D-672 NHCH 2 CF 3 SMe Et 4-NH 2 D-623 NHEt SEt Et 4-NH 2 D-673 NHCH 2 CF 3 SEt Et 4-NH 2 D-624 NHEt S-n-Pr Et 4-NH 2 D-674 NHCH 2 CF 3 S-n-Pr Et 4-NH 2 D-625 NHEt S-i-Pr Et 4-NH 2 D-675 NHCH 2 CF 3 S-i-Pr Et 4-NH 2 D-626 NHEt S-n-Bu Et 4-NH 2 D-676 NHCH 2 CF 3 S-n-Bu Et 4-NH 2 D-627 NHEt S-allyl Et 4-NH 2 D-677 NHCH 2 CF 3 S-allyl Et 4-NH 2 D-628 NHEt S-propargyl Et 4-NH 2 D-678 NHCH 2 CF 3 S-propargyl Et 4-NH 2 D-629 NHEt SCH 2 CF 3 Et 4-NH 2 D-679 NHCH 2 CF 3 SCH 2 CF 3 Et 4-NH 2 D-630 NHEt SCH 2 CH 2 F Et 4-NH 2 D-680 NHCH 2 CF 3 SCH 2 CH 2 F Et 4-NH 2 D-631 NHPr SH Et 4-NH 2 D-681 NHCH 2 CH 2 F SH Et 4-NH 2 D-632 NHPr SMe Et 4-NH 2 D-682 NHCH 2 CH 2 F SMe Et 4-NH 2 D-633 NHPr SEt Et 4-NH 2 D-683 NHCH 2 CH 2 F SEt Et 4-NH 2 D-634 NHPr S-n-Pr Et 4-NH 2 D-684 NHCH 2 CH 2 F S-n-Pr Et 4-NH 2 D-635 NHPr S-i-Pr Et 4-NH 2 D-685 NHCH 2 CH 2 F S-i-Pr Et 4-NH 2 D-636 NHPr S-n-Bu Et 4-NH 2 D-686 NHCH 2 CH 2 F S-n-Bu Et 4-NH 2 D-637 NHPr S-allyl Et 4-NH 2 D-687 NHCH 2 CH 2 F S-allyl Et 4-NH 2 D-638 NHPr S-propargyl Et 4-NH 2 D-688 NHCH 2 CH 2 F S-propargyl Et 4-NH 2 D-639 NHPr SCH 2 CF 3 Et 4-NH 2 D-689 NHCH 2 CH 2 F SCH 2 CF 3 Et 4-NH 2 D-640 NHPr SCH 2 CH 2 F Et 4-NH 2 D-690 NHCH 2 CH 2 F SCH 2 CH 2 F Et 4-NH 2 D-641 NH-i-Pr SH Et 4-NH 2 D-691 NH-n-Bu SH Et 4-NH 2 D-642 NH-i-Pr SMe Et 4-NH 2 D-692 NH-n-Bu SMe Et 4-NH 2 D-643 NH-i-Pr SEt Et 4-NH 2 D-693 NH-n-Bu SEt Et 4-NH 2 D-644 NH-i-Pr S-n-Pr Et 4-NH 2 D-694 NH-n-Bu S-n-Pr Et 4-NH 2 D-645 NH-i-Pr S-i-Pr Et 4-NH 2 D-695 NH-n-Bu S-i-Pr Et 4-NH 2 D-646 NH-i-Pr S-n-Bu Et 4-NH 2 D-696 NH-n-Bu S-n-Bu Et 4-NH 2 D-647 NH-i-Pr S-allyl Et 4-NH 2 D-697 NH-n-Bu S-allyl Et 4-NH 2 D-648 NH-i-Pr S-propargyl Et 4-NH 2 D-698 NH-n-Bu S-propargyl Et 4-NH 2 D-649 NH-i-Pr SCH 2 CF 3 Et 4-NH 2 D-699 NH-n-Bu SCH 2 CF 3 Et 4-NH 2 D-650 NH-i-Pr SCH 2 CH 2 F Et 4-NH 2 D-700 NH-n-Bu SCH 2 CH 2 F Et 4-NH 2 Compound No. R 15 R 16 R 17 R 18 Compound No. R 15 R 16 R 17 R 18 D-701 NH 2 SH Me 4-NO 2 D-751 NH-allyl SH Me 4-NO 2 D-702 NH 2 SMe Me 4-OMe D-752 NH-allyl SMe Me 4-NO 2 D-703 NH 2 SEt Me 4-NO 2 D-753 NH-allyl SEt Me 4-NO 2 D-704 NH 2 S-n-Pr Me 4-NO 2 D-754 NH-allyl S-n-Pr Me 4-NO 2 D-705 NH 2 S-i-Pr Me 4-NO 2 D-755 NH-allyl S-i-Pr Me 4-NO 2 D-706 NH 2 S-n-Bu Me 4-NO 2 D-756 NH-allyl S-n-Bu Me 4-NO 2 D-707 NH 2 S-allyl Me 4-NO 2 D-757 NH-allyl S-allyl Me 4-NO 2 D-708 NH 2 S-propargyl Me 4-NO 2 D-758 NH-allyl S-Propargyl Me 4-NO 2 D-709 NH 2 SCH 2 CF 3 Me 4-NO 2 D-759 NH-allyl SCH 2 CF 3 Me 4-NO 2 D-710 NH 2 SCH 2 CH 2 F Me 4-NO 2 D-760 NH-allyl SCH 2 CH 2 F Me 4-NO 2 D-711 NHMe SH Me 4-NO 2 D-761 NH-prapargyl SH Me 4-NO 2 D-712 NHMe SMe Me 4-OMe D-762 NH-propargyl SMe Me 4-NO 2 D-713 NHMe SEt Me 4-OMe D-763 NH-propargyl SEt Me 4-NO 2 D-714 NHMe S-n-Pr Me 4-OMe D-764 NH-propargyl S-n-Pr Me 4-NO 2 D-715 NHMe S-i-Pr Me 4-NO 2 D-765 NH-propargyl S-i-Pr Me 4-NO 2 D-716 NHMe S-n-Bu Me 4-NO 2 D-766 NH-propargyl S-n-Bu Me 4-NO 2 D-717 NHMe S-allyl Me 4-NO 2 D-767 NH-propargyl S-allyl Me 4-NO 2 D-718 NHMe S-propargyl Me 4-NO 2 D-768 NH-propargyl S-propargyl Me 4-NO 2 D-719 NHMe SCH 2 CF 3 Me 4-NO 2 D-769 NH-propargyl SCH 2 CF 3 Me 4-NO 2 D-720 NHMe SCH 2 CH 2 F Me 4-NO 2 D-770 NH-propargyl SCH 2 CH 2 F Me 4-NO 2 D-721 NHEt SH Me 4-NO 2 D-771 NHCH 2 CF 3 SH Me 4-NO 2 D-722 NHEt SMe Me 4-OMe D-772 NHCH 2 CF 3 SMe Me 4-OMe D-723 NHEt SEt Me 4-OMe D-773 NHCH 2 CF 3 SEt Me 4-NO 2 D-724 NHEt S-n-Pr Me 4-OMe D-774 NHCH 2 CF 3 S-n-Pr Me 4-NO 2 D-725 NHEt S-i-Pr Me 4-NO 2 D-775 NHCH 2 CF 3 S-i-Pr Me 4-NO 2 D-726 NHEt S-n-Bu Me 4-NO 2 D-776 NHCH 2 CF 3 S-n-Bu Me 4-NO 2 D-727 NHEt S-allyl Me 4-NO 2 D-777 NHCH 2 CF 3 S-allyl Me 4-NO 2 D-728 NHEt S-propargyl Me 4-NO 2 D-778, NHCH 2 CF 3 S-propargyl Me 4-NO 2 D-729 NHEt SCH 2 CF 3 Me 4-NO 2 D-779 NHCH 2 CF 3 SCH 2 CF 3 Me 4-NO 2 D-730 NHEt SCH 2 CH 2 F Me 4-NO 2 D-780 NHCH 2 CF 3 . SCH 2 CH 2 F Me 4-NO 2 D-731 NHPr SH Me 4-NO 2 D-781 NHCH 2 CH 2 F SH Me 4-NO 2 D-732 NHPr SMe Me 4-OMe D-782 NHCH 2 CH 2 F SMe Me 4-NO 2 D-733 NHPr SEt Me 4-NO 2 D-783 NHCH 2 CH 2 F SEt Me 4-NO 2 D-734 NHPr S-n-Pr Me 4-NO 2 D-784 NHCH 2 CH 2 F S-n-Pr Me 4-NO 2 D-735 NHPr S-i-Pr Me 4-NO 2 D-785 NHCH 2 CH 2 F S-i-Pr Me 4-NO 2 D-736 NHPr S-n-Bu Me 4-NO 2 D-786 NHCH 2 CH 2 F S-n-Bu Me 4-NO 2 D-737 NHPr S-allyl Me 4-NO 2 D-787 NHCH 2 CH 2 F S-allyl Me 4-NO 2 D-738 NHPr S-propargyl Me 4-NO 2 D-788 NHCH 2 CH 2 F S-propargyl Me 4-NO 2 D-739 NHPr SCH 2 CF 3 Me 4-NO 2 D-789 NHCH 2 CH 2 F SCH 2 CF 3 Me 4-NO 2 D-740 NHPr SCH 2 CH 2 F Me 4-NO 2 D-790 NHCH 2 CH 2 F SCH 2 CH 2 F Me 4-NO 2 D-741 NH-i-Pr SH Me 4-NO 2 D-791 NH-n-Bu SH Me 4-NO 2 D-742 NH-i-Pr SMe Me 4-NO 2 D-792 NH-n-Bu SMe Me 4-NO 2 D-743 NH-i-Pr SEt Me 4-NO 2 D-793 NH-n-Bu SEt Me 4-NO 2 D-744 NH-i-Pr S-n-Pr Me 4-NO 2 D-794 NH-n-Bu S-n-Pr Me 4-NO 2 D-745 NH-i-Pr S-i-Pr Me 4-NO 2 D-795 NH-n-Bu S-i-Pr Me 4-NO 2 D-746 NH-i-Pr S-n-Bu Me 4-NO 2 D.796 NH-n-Bu S-n-Bu Me 4-NO 2 D-747 NH-i-Pr S-allyl Me 4-NO 2 D-797 NH-n-Bu S-allyl Me 4-NO 2 D.748 NH-i-Pr S-propargyl Me 4-NO 2 D-798 NH-n-Bu S-propargyl Me 4-NO 2 D-749 NH-i-Pr SCH 2 CF 3 Me 4-NO 2 D-799 NH-n-Bu SCH 2 CF 3 Me 4-NO 2 D-750 NH-i-Pr SCH 2 CH 2 F Me 4-NO 2 D-800 NH-n-Bu SCH 2 CH 2 F Me 4-NO 2 Compound No. R 15 R 16 R 17 R 18 Compound No. R 15 R 16 R 17 R 18 D-801 NH 2 SH Me 4-NH 2 D-851 NH-allyl SH Me 4-NH 2 D-802 NH 2 SMe Me 4-OMe D-852 NH-allyl SMe Me 4-NH 2 D-803 NH 2 SEt Me 4-NH 2 D-853 NH-allyl SEt Me 4-NH 2 D-804 NH 2 S-n-Pr Me 4-NH 2 D-854 NH-allyl S-n-Pr Me 4-NH 2 D-805 NH 2 S-i-Pr Me 4-NH 2 D-855 NH-allyl S-i-Pr Me 4-NH 2 D-806 NH 2 S-n-Bu Me 4-NH 2 D-856 NH-allyl S-n-Bu Me 4-NH 2 D-807 NH 2 S-allyl Me 4-NH 2 D-857 NH-allyl S-allyl Me 4-NH 2 D-808 NH 2 S-propargyl Me 4-NH 2 D-858 NH-allyl S-propargyl Me 4-NH 2 D-809 NH 2 SCH 2 CF 3 Me 4-NH 2 D-859 NH-allyl SCH 2 CF 3 Me 4-NH 2 D-810 NH 2 SCH 2 CH 2 F Me 4-NH 2 D-860 NH-allyl SCH 2 CH 2 F Me 4-NH 2 D-811 NHMe SH Me 4-NH 2 D-861 NH-propargyl SH Me 4-NH 2 D-812 NHMe SMe Me 4-OMe D-862 NH-propargyl SMe Me 4-NH 2 D-813 NHMe SEt Me 4-OMe D-863 NH-propargyl SEt Me 4-NH 2 D-814 NHMe S-n-Pr Me 4-OMe D-864 NH-propargyl S-n-Pr Me 4-NH 2 D-815 NHMe S-i-Pr Me 4-NH 2 D-865 NH-propargyl S-i-Pr Me 4-NH 2 D-816 NHMe S-n-Bu Me 4-NH 2 D-866 NH-propargyl S-n-Bu Me 4-NH 2 D-817 NHMe S-allyl Me 4-NH 2 D-867 NH-propargyl S-allyl Me 4-NH 2 D-818 NHMe S-propargyl Me 4-NH 2 D-868 NH-propargyl S-propargyl Me 4-NH 2 D-819 NHMe SCH 2 CF 3 Me 4-NH 2 D-869 NH-propargyl SCH 2 CF 3 Me 4-NH 2 D-820 NHMe SCH 2 CH 2 F Me 4-NH 2 D-870 NH-propargyl SCH 2 CH 2 F Me 4-NH 2 D-821 NHEt SH Me 4-NH 2 D-871 NHCH 2 CF 3 SH Me 4-NH 2 D-822 NHEt SMe Me 4-OMe D-872 NHCH 2 CF 3 SMe Me 4-OMe D-823 NHEt SEt Me 4-OMe D-873 NHCH 2 CF 3 SEt Me 4-NH 2 D-824 NHEt S-n-Pr Me 4-OMe D-874 NHCH 2 CF 3 S-n-Pr Me 4-NH 2 D-825 NHEt S-i-Pr Me 4-NH 2 D-875 NHCH 2 CF 3 S-i-Pr Me 4-NH 2 D-826 NHEt S-n-Bu Me 4-NH 2 D-876 NHCH 2 CF 3 S-n-Bu Me 4-NH 2 D-827 NHEt S-allyl Me 4-NH 2 D-877 NHCH 2 CF 3 S-allyl Me 4-NH 2 D-828 NHEt S-propargyl Me 4-NH 2 D-878 NHCH 2 CF 3 S-propargyl Me 4-NH 2 D-829 NHEt SCH 2 CF 3 Me 4-NH 2 D-879 NHCH 2 CF 3 SCH 2 CF 3 Me 4-NH 2 D-830 NHEt SCH 2 CH 2 F Me 4-NH 2 D-880 NHCH 2 CF 3 SCH 2 CH 2 F Me 4-NH 2 D-831 NHPr SH Me 4-NH 2 D-881 NHCH 2 CH 2 F SH Me 4-NH 2 D-832 NHPr SMe Me 4-OMe D-882 NHCH 2 CH 2 F SMe Me 4-NH 2 D-833 NHPr SEt Me 4-NH 2 D-883 NHCH 2 CH 2 F SEt Me 4-NH 2 D-834 NHPr S-n-Pr Me 4-NH 2 D-884 NHCH 2 CH 2 F S-n-Pr Me 4-NH 2 D-835 NHPr S-i-Pr Me 4-NH 2 D-885 NHCH 2 CH 2 F S-i-Pr Me 4-NH 2 D-836 NHPr S-n-Bu Me 4-NH 2 D-886 NHCH 2 CH 2 F S-n-Bu Me 4-NH 2 D-837 NHPr S-allyl Me 4-NH 2 D-887 NHCH 2 CH 2 F S-allyl Me 4-NH 2 D-838 NHPr S-propargyl Me 4-NH 2 D-888 NHCH 2 CH 2 F S-propargyl Me 4-NH 2 D-839 NHPr SCH 2 CF 3 Me 4-NH 2 D-889 NHCH 2 CH 2 F SCH 2 CF 3 Me 4-NH 2 D-840 NHPr SCH 2 CH 2 F Me 4-NH 2 D-890 NHCH 2 CH 2 F SCH 2 CH 2 F Me 4-NH 2 D-841 NH-i-Pr SH Me 4-NH 2 D-891 NH-n-Bu SH Me 4-NH 2 D-842 NH-i-Pr SMe Me 4-NH 2 D-892 NH-n-Bu SMe Me 4-NH 2 D-843 NH-i-Pr SEt Me 4-NH 2 D-893 NH-n-Bu SEt Me 4-NH 2 D-844 NH-i-Pr S-n-Pr Me 4-NH 2 D-894 NH-n-Bu S-n-Pr Me 4-NH 2 D-845 NH-i-Pr S-i-Pr Me 4-NH 2 D-895 NH-n-Bu S-i-Pr Me 4-NH 2 D-846 NH-i-Pr S-n-Bu Me 4-NH 2 D-896 NH-n-Bu S-n-Bu Me 4-NH 2 D-847 NH-i-Pr S-allyl Me 4-NH 2 D-897 NH-n-Bu S-allyl Me 4-NH 2 D-848 NH-i-Pr S-propargyl Me 4-NH 2 D-898 NH-n-Bu S-propargyl Me 4-NH 2 D-849 NH-i-Pr SCH 2 CF 3 Me 4-NH 2 D-899 NH-n-Bu SCH 2 CF 3 Me 4-NH 2 D-850 NH-i-Pr SCH 2 CH 2 F Me 4-NH 2 D.900 NH-n-Bu SCH 2 CH 2 F Me 4-NH 2 Compound No. R 15 R 16 R 17 R 18 Compound No. R 15 R 18 R 17 R 18 D-901 NH 2 OH H 4-NH 2 D-951 NH-allyl OH H 4-NH 2 D-902 NH 2 OMe H 4-NH 2 D-952 NH-allyl OMe H 4-NH 2 D-903 NH 2 OEt H 4-NH 2 D-953 NH-allyl OEt H 4-NH 2 D-904 NH 2 O-n-Pr H 4-NH 2 D.954 NH-allyl O-n-Pr H 4-NH 2 D-905 NH 2 O-i-Pr H 4-NH 2 D-955 NH-allyl O-i-Pr H 4-NH 2 D-906 NH 2 O-n-Bu H 4-NH 2 D-956 NH-allyl O-n-Bu H 4-NH 2 D-907 NH 2 O-allyl H 4-NH 2 D-957 NH-allyl O-allyl H 4-NH 2 D-908 NH 2 O-propargyl H 4-NH 2 D-958 NH-allyl O-propargyl H 4-NH 2 D-909 NH 2 OCH 2 CF 3 H 4-NH 2 D-959 NH-allyl OCH 2 CF 3 H 4-NH 2 D-910 NH 2 OCH 2 CH 2 F H 4-NH 2 D-960 NH-allyl OCH 2 CH 2 F H 4-NH 2 D-911 NHMe OH H 4-NH 2 D-961 NH-propargyl OH H 4-NH 2 D-912 NHMe OMe H 4-NH 2 D-962 NH-propargyl OMe H 4-NH 2 D-913 NHMe OEt H 4-NH 2 D-963 NH-propargyl OEt H 4-NH 2 D-914 NHMe O-n-Pr H 4-NH 2 D-964 NH-propargyl O-n-Pr H 4-NH 2 D-915 NHMe O-i-Pr H 4-NH 2 D-965 NH-propargyl O-i-Pr H 4=NH 2 D-916 NHMe O-n-Bu H 4-NH 2 D-966 NH-propargyl O-n-Bu H 4-NH 2 D-917 NHMe O-allyl H 4-NH 2 D-967 NH-propargyl O-allyl H 4-NH 2 D-918 NHMe O-propargyl H 4-NH 2 D-968 NH-propargyl O-propargyl H 4-NH 2 D-919 NHMe OCH 2 CF 3 H 4-NH 2 D-969 NH-propargyl OCH 2 CF 3 H 4-NH 2 D-920 NHMe OCH 2 CH 2 F H 4-NH 2 D-970 NH-propargyl OCH 2 CH 2 F H 4-NH 2 D-921 NHEt OH H 4-NH 2 D-971 NHCH 2 CF 3 OH H 4-NH 2 D-922 NHEt OMe H 4-NH 2 D-972 NHCH 2 CF 3 OMe H 4-NH 2 D-923 NHEt OEt H 4-NH 2 D-973 NHCH 2 CF 3 OEt H 4-NH 2 D-924 NHEt O-n-Pr H 4-NH 2 D-974 NHCH 2 CF 3 O-n-Pr H 4-NH 2 D-925 NHEt O-i-Pr H 4-NH 2 D-975 NHCH 2 CF 3 O-i-Pr H 4-NH 2 D-926 NHEt O-n-Bu H 4-NH 2 D-976 NHCH 2 CF 3 O-n-Bu H 4-NH 2 D-927 NHEt O-allyl H 4-NH 2 D-977 NHCH 2 CFs O-allyl H 4-NH 2 D-928 NHEt 0-propargyl H 4-NH 2 D-978 NHCH 2 CF 3 O-propargyl H 4-NH 2 D-929 NHEt OCH 2 CF 3 H 4-NH 2 D-979 NHCH 2 CF 3 OCH 2 CF 3 H 4-NH 2 D-930 NHEt OCH 2 CH 2 F H 4-NH 2 D-980 NHCH 2 CF 3 OCH 2 CH 2 F H 4-NH 2 D-931 NHPr OH H 4-NH 2 D-981 NHCH 2 CH 2 F OH H 4-NH 2 D-932 NHPr OMe H 4-NH 2 D-982 NHCH 2 CH 2 F OMe H 4-NH 2 D-933 NHPr OEt H 4-NHz D-983 NHCH 2 CHaF. OEt H 4-NH 2 D-934 NHPr O-n-Pr H 4-NH 2 D-984 NHCH 2 CH 2 F O-n-Pr H 4-NH 2 D-935 NHPr O-i-Pr H 4-NH 2 D-985 NHCH 2 CH 2 F O-i-Pr H 4-NH 2 D-936 NHPr O-n-Bu H 4-NH 2 D-986 NHCH 2 CH 2 F O-n-Bu H 4-NH 2 D-937 NHPr O-allyl H 4-NH 2 D-987 NHCH 2 CH 2 F O-allyl H 4-NH 2 D-938 NHPr O-propargyl H 4-NH 2 D-988 NHCH 2 CH 2 F O-propargyl H 4-NH 2 D-939 NHPr OCH 2 CF 3 H 4-NH 2 D-989 NHCH 2 CH 2 F OCH 2 CF 3 H 4-NH 2 D-940 NHPr OCH 2 CH 3 F H 4-NH 2 D-990 NHCH 2 CH 2 F OCH 2 CH 2 F H 4-NH 2 D-941 NH-i-Pr OH H 4-NH 2 D-991 NH-n-Bu OH H 4-NH 2 D-942 NH-i-Pr OMe H 4-NH 2 D-992 NH-n-Bu OMe H 4-NH 2 D-943 NH-i-Pr OEt H 4-NH 2 D-993 NH-n-Bu OEt H 4-NH 2 D-944 NH-i-Pr O-n-Pr H 4-NH 2 D-994 NH-n-Bu O-n-Pr H 4-NH 2 D-945 NH-i-Pr O-i-Pr H 4-NH 2 D-995 NH-n-Bu " O-i-Pr H 4-NH 2 D-946 NH-i-Pr O-n-Bu H 4-NH 2 D-996 NH-n-Bu O-n-Bu H 4-NH 2 D-947 NH-i-Pr O-allyl H 4-NH 2 D-997 NH-n-Bu O-allyl H 4-NH 2 D-948 NH-i-Pr O-propargyl H 4-NH 2 D-998 NH-n-Bu O-propargyl H 4-NH 2 D-949 NH-i-Pr OCH 2 CF 3 H 4-NH 2 D-999 NH-n-Bu OCH 2 CFs H 4-NH 2 D-950 NH-i-Pr OCH 2 CH 2 F H 4-NH 2 D-1000 NH-n-Bu OCH 2 CH 2 F H 4-NH 2 Compound No. R15 R 16 R 17 R 18 Compound No. R 15 R 16 R 17 R 18 D-1001 NH 2 OH H 4-NO 2 D-1051 NH-allyl OH H 4-NO 2 D-1002 NH 2 OMe H 4-NO 2 D-1052 NH-allyl OMe H 4-NO 2 D-1003 NH 2 OEt H 4-NO 2 D-1053 NH-allyl OEt H 4-NO 2 D-1004 NH 2 O-n-Pr H 4-NO 2 D-1054 NH-allyl O-n-Pr H 4-NO 2 D-1005 NH 2 O-i-Pr H 4-NO 2 D-1055 NH-allyl O-i-Pr H 4-NO 2 D-1006 NH 2 O-n-Bu H 4-NO 2 D-1056 NH-allyl O-n-Bu H 4-NO 2 D-1007 NH 2 O-allvl H 4-NO 2 D-1057 NH-allyl O-allyl H 4-NO 2 D-1008 NHz O-propargyl H 4-NO 2 D-1058 NH-allyl O-proparsvl H 4-NO 2 D-1009 NH 2 OCH 2 CF 3 H 4-NO 2 D-1059 NH-allyl OCH 2 CF 3 H 4-NO 2 D-1010 NH 2 OCH 2 CH 2 F H 4-NO 2 D-1060 NH-allyl OCH 2 CH 2 F H 4-NO 2 D1011 NHMe OH H 4-NO 2 D-1061 NH-propargyl OR H 4-NO 2 D-1012 NHMe OMe H 4-NO 2 D-1062 NH-propargyl OMe H 4-NO 2 D-1013 NHMe OEt H 4-NO 2 D-1063 NH-propargyl OEt H 4-NO 2 D-1014 NHMe O-n-Pr H 4-NO 2 D-1064 NH-propargyl O-n-Pr H 4-NO 2 D-1015 NHMe O-i-Pr H 4-NO 2 D-1065 NH-propargyl O-i-Pr H 4-NO 2 D-1016 NHMe O-n-Bu H 4-NO 2 D-1066 NH-propargyl O-n-Bu H 4-NO 2 D-1017 NHMe O-allyl H 4-NO 2 D-1067 NH-propargyl O-allyl H 4-NO 2 D-1018 NHMe O-propargyl H 4-NO 2 D-1068 NH-propargyl O-propargyl H 4-NO 2 D-1019 NHMe OCH 2 CF 3 H 4-NO 2 D-1069 NH-propargyl OCH 2 CF 3 H 4-NO 2 D-1020 NHMe OCH 2 CH 2 F H 4-NO 2 D-1070 NH-propargyl OCH 2 CH 2 F H 4-NO 2 D-1021 NHEt OH H 4-NO 2 D-1071 NHCH 2 CF 3 OH H 4-NO 2 D-1022 NHEt OMe H 4-NO 2 D-1072 NHCH 2 CF 3 OMe H 4-NO 2 D-1023 NHEt OEt H 4-NO 2 D-1073 NHCH 2 CF 3 OEt H 4-NO 2 D-1024 NHEt O-n-Pr H 4-NO 2 D-1074 NHCH 2 CF 3 O-n-Pr H 4-NO 2 D-1025 NHEt O-i-Pr H 4-NO 2 D-1075 NHCH 2 CF 3 O-i-Pr H 4-NO 2 D-1026 NHEt O-n-Bu H 4-NO 2 D-1076 NHCH 2 CF 3 O-n-Bu H 4-NO 2 D-1027 NHEt O-allyl H 4-NO 2 D-1077 NHCH 2 CF 3 O-allyl H 4-NO 2 D-1028 NHEt O-propargyl H 4-NO 2 D-1078 NHCH 2 CF 3 O-propargyl H 4-NO 2 D-1029 NHEt OCH 2 CF 3 H 4-NO 2 D-1079 NHCH 2 CF 3 OCH 2 CF 3 H 4-NO 2 D-1030 NHEt OCH 2 CH 2 F H 4-NO 2 D-1080 NHCH 2 CF 3 OCH 2 CH 2 F H 4-NO 2 D-1031 NHPr OH H 4-NO 2 D-1081 NHCH 2 CH 2 F OH H 4-NO 2 D-1032 NHPr OMe H 4-NO 2 D-1082 NHCH 2 CH 2 F OMe H 4-NO 2 D-1033 NHPr OEt H 4-NO 2 D-1083 NHCH 2 CH 2 F OEt H 4-NO 2 D-1034 NHPr O-n-Pr H 4-NO 2 D-1084 NHCH 2 CH 2 F O-n-Pr H 4-NO 2 D-1035 NHPr O-i-Pr H 4-NO 2 D-1085 NHCH 2 CH 2 F O i-Pr H 4-NO 2 D-1036 NHPr O-n-Bu H 4-NO 2 D-1086 NHCH 2 CH 2 F O-n-Bu H 4-NO 2 D-1037 NHPr O-allyl H 4-NO 2 D-1087 NHCH 2 CH 2 F O-allyl H 4-NO 2 D-1038 NHPr O-propargyl H 4-NO 2 D-1088 NHCH 2 CH 2 F O-proparsyl H 4-NO 2 D-1039 NHPr OCH 2 CF 3 H 4-NO 2 D-1089 NHCH 2 CH 2 F OCH 2 CF 3 H 4-NO 2 D-1040 NHPr OCH 2 CH 2 F H 4-NO 2 D-1090 NHCH 2 CH 2 F OCH 2 CH 2 F H 4-NO 2 D-1041 NH-i-Pr OH H 4-NO 2 D-1091 NH-n-Bu OH H 4-NO 2 D-1042 NH-i-Pr OMe H 4-NO 2 D-1092 NH-n-Bu OMe H 4-NO 2 D-1043 NH-i-Pr OEt H 4-NO 2 D.1093 NH-n-Bu OEt H 4-NO 2 D-1044 NH-i-Pr O-n-Pr H 4-NO 2 D-1094 NH-n-Bu O-n-Pr H 4-NO 2 D-1045 NH-i-Pr O-i-Pr H 4-NO 2 D-1095 NH-n-Bu i O-i-Pr H 4-NO 2 D-1046 NH-i-Pr O-n-Bu H 4-NO 2 D-1096 NH-n-Bu O-n-Bu H 4-NO 2 D-1047 NH-i-Pr O-allyl H 4-NO 2 D-1097 NH-n-Bu O-allyl H 4-NO 2 D-1048 NH-i-Pr O-propargyl H 4-NO 2 D-1098 NH-n-Bu O-propargyl H 4-NO 2 D-1049 NH-i-Pr OCH 2 CF 3 H 4-NO 2 D-1099 NH-n-Bu OCH 2 CF 3 H 4-NO 2 D-1050 NH-i-Pr OCH 2 CH 2 F H 4-NO 2 D-1100 NH-n-Bu OCH 2 CH 2 F H 4-NO 2 Compound No. R 15 R 16 R 17 R 18 Compound No. R 15 R 16 R 17 R 18 D-1101 NH 2 OH Me 4-NH 2 D-1151 NH-allyl OH Me 4-NH 2 D-1102 NH 2 OMe Me 4-NH 2 D-1152 NH-allyl OMe Me 4-NH 2 D-1103 NH 2 OEt Me 4-NH 2 D-1153 NH-allyl OEt Me 4-NH 2 D-1104 NH 2 O-n-Pr Me 4-NH 2 D-1154 NH-allyl O-n-Pr Me 4-NH 2 D-1105 NH 2 O-i-Pr Me 4-NH 2 D-1155 NH-allyl O-i-Pr Me 4-NH 2 D-1106 NH 2 O-n-Bu Me 4-NH 2 D-1156 NH-allyl O-n-Bu Me 4-NH 2 D-1107 NH 2 O-allyl Me 4-NH 2 D-1157 NH-allyl O-allyl Me 4-NH 2 D-1108 NH 2 O-propargyl Me 4-NH 2 D-1158 NH-allyl O-propargyl Me 4-NH 2 D-1109 NH 2 OCH 2 CF 3 Me 4-NH 2 D-1159 NH-allyl OCH 2 CF 3 Me 4-NH 2 D-1110 NH 2 OCH 2 CH 2 F Me 4-NH 2 D-1160 NH-allyl OCH 2 CH 2 F Me 4-NH 2 D-1111 NHMe OH Me 4-NH 2 D-1161 NH-propargyl OH Me 4-NH 2 D-1112 NHMe OMe Me 4-NH 2 D-1162 NH-propargyl OMe Me 4-NH 2 D-1113 NHMe OEt Me 4-NH 2 D-1163 NH-propargyl OEt Me 4-NH 2 D-1114 NHMe O-n-Pr Me 4-NH 2 D-1164 NH-propargyl O-n-Pr Me 4-NH 2 D-1115 NHMe O-i-Pr Me 4-NH 2 D-1165 NH-propargyl O-i-Pr Me 4-NH 2 D-1116 NHMe O-n-Bu Me 4-NH 2 D-1166 NH-propargyl O-n-Bu Me 4-NH 2 D-1117 NHMe O-allyl Me 4-NH 2 D-1167 NH-propargyl O-allyl Me 4-NH 2 D-1118 NHMe O-propargyl Me 4-NH 2 D-1168 NH-propargyl O-proprargyl Me 4-NH 2 D-1119 NHMe OCH 2 CF 3 Me 4-NH 2 D-1169 NH-propargyl OCH 2 CF 3 Me 4-NH 2 D-1120 NHMe OCH 2 CH 2 F Me 4-NH 2 D-1170 NH-propargyl OCH 2 CH 2 F Me 4-NH 2 D-1121 NHEt OH Me 2-NH 2 D-1171 NHCH 2 CF 3 OH Me 4-NH 2 D-1122 NHEt OMe Me 4-NH 2 D-1172 NHCH 2 CF 3 OMe Me 4-NH 2 D-1123 NHEt OEt Me 4-NH 2 D-1173 NHCH 2 CF 3 OEt Me 4-NH 2 D-1124 NHEt O-n-Pr Me 4-NH 2 D-1174 NHCH 2 CF 3 O-n-Pr Me 4-NH 2 D-1125 NHEt O-i-Pr Me 4-NH 2 D-1175 NHCH 2 CF 3 O-i-Pr Me 4-NH 2 D-1126 NHEt O-n-Bu Me 4-NH 2 D-1176 NHCH 2 CF 3 O-n-Bu Me 4-NH 2 D-1127 NHEt O-allyl Me 4-NH 2 D-1177 NHCH 2 CF 3 O-allyl Me 4-NH 2 D-1128 NHEt O-propargyl Me 4-NH 2 D-1178 NHCH 2 CF 3 O-propargyl Me 4-NH 2 D-1129 NHEt OCH 2 CF 3 Me 4-NH 2 D-1179 NHCH 2 CF 3 OCH 2 CF 3 Me 4-NH 2 D-1130 NHEt OCH 2 CH 2 F Me 4-NH 2 D-1180 NHCH 2 CF 3 OCH 2 CH 2 F Me 4-NH 2 D-1131 NHPr OH Me 4-NH 2 D-1181 NHCH 2 CH 2 F OH Me 4-NH 2 D-1132 NHPr OMe Me 4-NH 2 D-1182 NHCH 2 CH 2 F OMe Me 4-NH 2 D-1133 NHPr OEt Me 4-NH 2 D-1183 NHCH 2 CH 2 F OEt Me 4-NH 2 D-1134 NHPr O-n-Pr Me 4-NH 2 D-1184 NHCH 2 CH 2 F O-n-Pr Me 4-NH 2 D-1135 NHPr O-i-Pr Me 4-NH 2 D-1185 NHCH 2 CH 2 F O-i-Pr Me 4-NH 2 D-1136 NHPr O-n-Bu Me 4-NH 2 D-1186 NHCH 2 CH 2 F O-n-Bu Me 4-NH 2 D-1137 NHPr O-allyl Me 4-NH 2 D-1187 NHCH 2 CH 2 F O-allyl Me 4-NH 2 D-1138 NHPr O-proparsyl Me 4-NH 2 D-1188 NHCH 2 CH 2 F O-propargyl Me 4-NH 2 D-1139 NHPr OCH 2 CF 3 Me 4-NH 2 D-1189 NHCH 2 CH 2 F OCH 2 CF 3 Me 4-NH 2 D-1140 NHPr OCH 2 CH 2 F Me 4-NH 2 D-1190 NHCH 2 CH 2 F OCH 2 CH 2 F Me 4-NH 2 D-1141 NH-i-Pr OH Me 4-NH 2 D-1191 NH-n-Bu OH Me 4-NH 2 D-1142 NH-i-Pr OMe Me 4-NH 2 D-1192 NH-n-Bu OMe Me 4-NH 2 D-1143 NH-i-Pr OEt Me 4-NH 2 D-1193 NH-n-Bu OEt Me 4-NH 2 D-1144 NH-i-Pr O-n-Pr Me 4-NH 2 D-1194 NH-n-Bu O-n-Pr Me 4-NH 2 D-1145 NH-i-Pr O-i-Pr Me 4-NH 2 D-1195 NH-n-Bu O-i-Pr Me 4-NH 2 D-1146 NH-i-Pr O-n-Bu Me 4-NH 2 D-1196 NH-n-Bu O-n-Bu Me 4-NH 2 D-1147 NH-i-Pr O-allyl Me 4-NH 2 D-1197 NH-n-Bu O-allyl Me 4-NH 2 D-1148 NH-i-Pr O-propargyl Me 4-NH 2 D-1198 NH-n-Bu O-propargyl Me 4-NH 2 D-1149 NH-i-Pr OCH 2 CF 3 Me 4-NH 2 D-1199 NH-n-Bu OCH 2 CF 3 Me 4-NH 2 D-1150 NH-i-Pr OCH 2 CH 2 F Me 4-NH 2 D-1200 NH-n-Bu OCH 2 CH 2 F Me 4-NH 2 Compound No. R 15 R 16 R 17 R 18 Compound No. R 15 R 16 R 17 R 18 D-1201 NH 2 OH Me 4-NO 2 D-1251 NH-allyl OH Me 4-NO 2 D-1202 NH 2 OMe Me 4-NO 2 D-1252 NH-allyl OMe Me 4-NO 2 D-1203 NH 2 OEt Me 4-NO 2 D-1253 NH-allyl OEt Me 4-NO 2 D-1204 NH 2 O-n-Pr Me 4-NO 2 D-1254 NH-allyl O-a-Pr Me 4-NO 2 D-1205 NH 2 O-i-Pr Me 4-NO 2 D-1255 NH-allyl O-i-Pr Me 4-NO 2 D-1206 NH 2 O-n-Bu Me 4-NO 2 D-1256 NH-allyl O-n-Bu Me 4-NO 2 D-1207 NH 2 O-allyl Me 4-NO 2 D-1257 NH-allyl O-allyl Me 4-NO 2 D-1208 NH 2 O-propargyl Me 4-NO 2 D-1258 NH-allyl O-propargyl Me 4-NO 2 D-1209 NH 2 OCH 2 CF 3 Me 4-NO 2 D-1259 NH-allyl OCH 2 CF 3 Me 4-NO 2 D-1210 NH 2 OCH 2 CH 2 F Me 4-NO 2 D-1260 NH-allyl OCH 2 CH 2 F Me 4-NO 2 D-1211 NHMe OH Me 4-NO 2 D-1261 NH-propargyl OH Me 4-NO 2 D-1212 NHMe OMe Me 4-OMe D-1262 NH-propargyl OMe Me 4-NO 2 D-1213 NHMe OEt Me 4-Cl D-1263 NH-propargyl OEt Me 4-NO 2 D-1214 NHMe O-n-Pr Me 4-NO2 D-1264 NH-propargyl O-n-Pr Me 4-NO 2 D-1215 NHMe O-i-Pr Me 4-OMe D-1265 NH-propargyl O-i-Pr Me 4-NO 2 D-1216 NHMe O-n-Bu Me 4-NO 2 D-1266 NH-propargyl O-n-Bu Me 4-NO 2 D-1217 NHMe O-allyl Me 4-NO 2 D-1267 NH-propargyl O-allyl Me 4-NO 2 D-1218 NHMe O-propargyl Me 4-NO 2 D-1268 NH-propargyl O-propargyl Me 4.NO 2 D-1219 NHMe OCH 2 CF 3 Me 4-NO 2 D-1269 NH-propargyl OCH 2 CF 3 Me 4-NO 2 D-1220 NHMe OCH2CH2F Me 4-NOz D-1270 NH-proparyl OCH 2 CH 2 F Me 4-NO 2 D-1221 NHEt OH Me 4-Me D-1271 NHCH 2 CF 3 OH Me 4-NH 2 D-1222 NHEt OMe Me 4-OMe D-1272 NHCH 2 CF 3 OMe Me 4-NO 2 D-1223 NHEt OEt Me 4-OMe D-1273 NHCH 2 CF 3 OEt Me 4-NO 2 D-1224 NHEt O-n-Pr Me 4-NO 2 D-1274 NHCH 2 CF 3 O-n-Pr Me 4-NO 2 D-1225 NHEt O-i-Pr Me 4-OMe D-1275 NHCH 2 CF 3 O-i-Pr Me 4-NO 2 D-1226 NHEt O-n-Bu Me 4-NO 2 D-1276 NHCH 2 CF 3 O-n-Bu Me 4-NO 2 D-1227 NHEt O-allyl Me 4-NO 2 D-1277 NHCH 2 CF 3 O-allyl Me 4-NO 2 D-1228 NHEt O-propargyl Me 4-NO 2 D-1278 NHCH 2 CF 3 O-propargyl Me 4-NO 2 D-1229 NHEt OCH 2 CF 3 Me 4-NO 2 D-1279 NHCH 2 CF 3 OCH 2 CF 3 Me 4-NO 2 D-1230 NHEt OCH 2 CH 2 F Me 4-NO 2 D-1280 NHCH 2 CF 3 OCH 2 CH 2 F Me 4-NO 2 D-1231 NHPr OH Me 4-OMe D-1281 NHCH 2 CH 3 F OH Me 4-NO 2 D-1232 NHPr OMe Me 4-NO 2 D-1282 NHCH 2 CH 2 F OMe Me 4-NO 2 D-1233 NHPr OEt Me 4-NO 2 D-1283 NHCH 2 CH 2 F OEt Me 4-NO 2 D-1234 NHPr O-n-Pr Me 4-NO 2 D-1284 NHCH 2 CH 2 F O-n-Pr Me 4-NO 2 D-1235 NHPr O-i-Pr Me 4-NO 2 D-1285 NHCH 2 CH 2 F O-i.Pr Me 4-NO 2 D-1236 NHPr O-n-Bu Me 4-NO 2 D-1286 NHCH 2 CH 2 F O-n.Bu Me 4-NO 2 D-1237 NHPr O-allyl Me 4-NO 2 D-1287 NHCH 2 CH 2 F O-allyl Me 4-NO 2 D-1238 NHPr O-propargyl Me 4-NO 2 D-1288 NHCH 2 CH 2 F O-propargyl Me 4-NO 2 D-1239 NHPr OCH 2 CF 3 Me 4-NO 2 D-1289 NHCH 2 CH 2 F OCH 2 CF 3 Me 4-NO 2 D-1240 NHPr OCH 2 CH 2 F Me 4-NO 2 D-1290 NHCH 2 CH 2 F OCH 2 CH 2 F Me 4-NO 2 D-1241 NH-i-Pr OH Me 4-NO 2 D-1291 NH-n-Bu OH Me 4-NO 2 D-1242 NH-i-Pr OMe Me 4-NO 2 D-1292 NH-n-Bu OMe Me 4-NO 2 D-1243 NH-i-Pr OEt Me 4-NO 2 D-1293 NH-n-Bu OEt Me 4-NO 2 D-1244 NH-i-Pr O-n-Pr Me 4-NO 2 D-1294 NH-u-Bu O-n-Pr Me 4-NO 2 D-1245 NH-i-Pr O-i-Pr Me 4-NO 2 D-1295 NH-n-Bu O-i-Pr Me 4-NO 2 D-1246 NH-i-Pr O-n-Bu Me 4-NO 2 D-1296 NH-n-Bu O-n-Bu Me 4-NO 2 D-1247 NH-i-Pr O-allyl Me 4-NO 2 D-1297 NH-n-Bu O-allyl Me 4-NO 2 D-1248 NH-i-Pr O-propargyl Me 4-NO 2 D-1298 NH-n-Bu O-propargyl Me 4-NO 2 D-1249 NH-i-Pr OCH 2 CF 3 Me 4-NO 2 D-1299 NH-n-Bu OCH 2 CF 3 Me 4-NO 2 D-1250 NH-i-Pr OCH 2 CH 2 F Me 4-NO 2 D-1300 NH-n-Bu OCH 2 CH 2 F Me 4-NO 2 Compound No. R 15 R 16 R 17 R 18 Compound No. R 15 R 16 R 17 R 18 D-1301 NH 2 NHOH Me 4-NH 2 D-1351 NH-propargyl NHOH Me 4-NH 2 D-1302 NH 2 NHOMe Me 4-NH 2 D-1352 NH-propargyl NHOMe Me 4-NH 2 D-1303 NH 2 NHOEt Me 4-NH 2 D-1353 NH-propargyl NHOEt Me 4-NH 2 D-1304 NH 2 NHNH 2 Me 4-NH 2 D-1354 NH-propargyl NHNH 2 Me 4-NH 2 D-1305 NH 2 NHNMe 2 Me 4-NH 2 D-1355 NH-propargyl NHNMe 2 Me 4-NH 2 D-1306 NH 2 NHNHMe Me 4-NH 2 D-1356 NH-propargyl NHNHMe Me 4-NH 2 D-1307 NH 2 NHNHEt Me 4-NH 2 D-1357 NH-propargyl NHNHEt Me 4-NH 2 D-1308 NH 2 NMeNH 2 Me 4-NH 2 D-1358 NH-propargyl NMeNH 2 Me 4-NH 2 D-1309 NH 2 NHCN Me 4-NH 2 D-1359 NH-propargyl NHCN Me 4-NH 2 D-1310 NH 2 NHNO 2 Me 4-NH 2 D-1360 NH-propargyl NHNO 2 Me 4-NH 2 D-1311 NHMe NHOH Me 4-NH 2 D-1361 NHCH 2 CH 2 F NHOH Me 4-NH 2 D-1312 NHMe NHOMe Me 4-NH 2 D-1362 NHCH 2 CH 2 F NHOMe Me 4-NH 2 D-1313 NHMe NHOEt Me 4-NH 2 D-1363 NHCH 2 CH 2 F NHOEt Me 4-NH 2 D-1314 NHMe NHNH 2 Me 4-NH 2 D-1364 NHCH 2 CH 2 F NHNH 2 Me 4-NH 2 D-1315 NHMe NHNMe 2 Me 4-NH 2 D-1365 NHCH 2 CH 2 F NHNMe 2 Me 4-NH 2 D-1316 NHMe NHNHMe Me 4-NH 2 D-1366 NHCH 2 CH 2 F NHNHMe Me 4-NH 2 D-1317 NHMe NHNHEt Me 4-NH 2 D-1367 NHCH 2 CH 2 F NHNHEt Me 4-NH 2 D-1318 NHMe NMeNH 2 Me 4-NH 2 D-1368 NHCH 2 CH 2 F NMeNH 2 Me 4-NH 2 D-1319 NHMe NHCN Me 4-NH 2 D-1369 NHCH 2 CH 2 F NHCN Me 4-NH 2 D-1320 NHMe NHNO 2 Me 4-NH 2 D-1370 NHCH 2 CH 2 F NHNO 2 Me 4-NH 2 D-1321 NHEt NHOH Me 4-NH 2 D-1371 NHCH 2 CF 3 NHOH Me 4-NH 2 D-1322 NHEt NHOMe Me 4-NH 2 D-1372 NHCH 2 CF 3 NHOMe Me 4-NH 2 D-1323 NHEt NHOEt Me 4-NH 2 D-1373 NHCH 2 CF 3 NHOEt Me 4-NH 2 D-1324 NHEt NHNH 2 Me 4-NH 2 D-1374 NHCH 2 CF 3 NHNH 2 Me 4-NH 2 D-1325 NHEt NHNMe 2 Me 4-NH 2 D-1375 NHCH 2 CF 3 NHNME 2 Me 4-NH 2 D-1326 NHEt NHNHMe Me 4-NH 2 D-1376 NHCH 2 CF 3 NHNHMe Me 4-NH 2 D-1327 NHEt NHNHEt Me 4-NH 2 D-1377 NHCH 2 CF 3 NHNHEt Me 4-NH 2 D-1328 NHEt NMENH 2 Me 4-NH 2 D-1378 NHCH 2 CF 3 NMeNH 2 Me 4-NH 2 D-1329 NHEt NHCN Me 4-NH 2 D-1379 NHCH 2 CF 3 NHCN Me 4-NH 2 D-1330 NHEt NHNO 2 Me 4-NH 2 D-1380 NHCH 2 CF 3 NHNO 2 Me 4-NH 2 D-1331 NH-i-Pr NHOH Me 4-NH 2 D-1381 SMe NHOH Me 4-NH 2 D-1332 NH-i-Pr NHOMe Me 4-NH 2 D-1382 SMe NHOMe Me 4-NH 2 D-1333 NH-i-Pr NHOEt Me 4-NH 2 D-1383 SMe NHOEt Me 4-NH 2 D-1334 NH-i-Pr NHNH 2 Me 4-NH 2 D-1384 SMe NHNH 2 Me 4-NH 2 D-1335 NH-i-Pr NHNMe 2 Me 4-NH 2 D-1385 SMe NHNMe 2 Me 4-NH 2 D-1336 NH-i-Pr NHNHMe Me 4-NH 2 D-1386 SMe NHNHMe Me 4-NH 2 D-1337 NH-i-Pr NHNHEt Me 4-NH 2 D-1387 SMe NHNHEt Me 4-NH 2 D-1338 NH-i-Pr NMeNH 2 Me 4-NH 2 D-1388 SMe NMeNH 2 Me 4-NH 2 D-1339 NH-i-Pr NHCN Me 4-NH 2 D-1389 SMe NHCN Me 4-NH 2 D-1340 NH-i-Pr NHNO 2 Me 4-NH 2 D-1390 SMe NHNO 2 Me 4-NH 2 D-1341 NH-allyl NHOH Me 4-NH 2 D-1391 SEt NHOH Me 4-NH 2 D-1342 NH-allyl NHOMe Me 4.NH 2 D-1392 SEt NHOMe Me 4-NH 2 D-1343 NH-allyl NHOEt Me 4-NH 2 D-1393 SEt NHOEt Me 4-NH 2 D-1344 NH-allyl NHNH 2 Me 4-NH 2 D-1394 SEt NHNH 2 Me 4-NH 2 D-1345 NH-allyl NHNMe 2 Me 4-NH 2 D-1395 SEt NHNMe 2 Me 4-NH 2 D-1346 NH-allyl NHNHMe Me 4-NH 2 D-1396 SEt NHNHMe Me 4-NH 2 D-1347 NH-allyl NHNHEt Me 4-NH 2 D-1397 SEt NHNHEt Me 4-NH 2 D-1348 NH-allyl NMeNH 2 Me 4-NH 2 D-1398 SEt NMeNH 2 Me 4-NH 2 D-1349 NH-allyl NHCN Me 4-NH 2 D-1399 SEt NHCN Me 4-NH 2 D-1350 NH-allyl NHNO 2 Me 4-NH 2 D-1400 SEt NHNO 2 Me 4-NH 2 Compound No. R 15 R 16 R 17 R 18 Compound No. R 15 R 16 R 17 R 18 D-1401 NH 2 NHOH Me 4-NO 2 D-1451 NH-propargyl NHOH Me 4-NO 2 D-1402 NH 2 NHOMe Me 4-NO 2 D-1452 NH-propargyl NHOMe Me 4-NO 2 D-1403 NH 2 NHOEt Me 4-NO 2 D-1453 NH-propargyl NHOEt Me 4-NO 2 D-1404 NH 2 NHNH 2 Me 4-NO 2 D-1454 NH-propargyl NHNH 2 Me 4-NO 2 D-1405 NH 2 NHNMe 2 Me 4-NO 2 D-1455 NH-propargyl NHNMe 2 Me 4-NO 2 D-1406 NH 2 NHNHMe Me 4-NO 2 D-1456 NH-propargyl NHNHMe Me 4-NO 2 D-1407 NH 2 NHNHEt Me 4-NO 2 D-1457 NH-propargyl NHNHEt Me 4-NO 2 D-1408 NH 2 NMeNH 2 Me 4-NO 2 D-1458 NH-propargyl NMeNH 2 Me 4-NO 2 D-1409 NH 2 NHCN Me 4-NO 2 D-1459 NH-propargyl NHCN Me 4-NO 2 D-1410 NH 2 NHNO 2 Me 4-NO 2 D-1460 NH-propargyl NHNO 2 Me 4-NO 2 D-1411 NHMe NHOH Me 4-NO 2 D-1461 NHCH 2 CH 2 F NHOH Me 4-NO 2 D-1412 NHMe NHOMe Me 4-Cl D-1462 NHCH 3 CH 2 F NHOMe Me 4-NO 2 D-1413 NHMe NHOEt Me 4-NO 2 D-1463 NHCH 2 CH 2 F NHOEt Me 4-NO 2 D-1414 NHMe NHNH 2 Me 4-NO 2 D-1464 NHCH 2 CH 2 F NHNH 2 Me 4-NO 2 D-1415 NHMe NHNMe 2 Me 4-NO 2 D-1465 NHCH 2 CH 2 F NHNMe 2 Me 4-NO 2 D-1416 NHMe NHNHMe Me 4-NO 2 D-1466 NHCH 2 CH 2 F NHNHMe Me 4-NO 2 D-1417 NHMe NHNHEt Me 4-NO 2 D-1467 NHCH 2 CH 2 F NHNHEt Me 4-NO 2 D-1418 NHMe NMeNH 2 Me 4-NO 2 D-1468 NHCH 2 CH 2 F NMeNH 2 Me 4-NO 2 D-1419 NHMe NHCN Me 4-NO 2 D-1469 NHCH 2 CH 2 F NHCN Me 4-NO 2 D-1420 NHMe NHNO 2 Me 4-NO 2 D-1470 NHCH 2 CH 2 F NHNO 2 Me 4-NO 2 D-1421 NHEt NHOH Me 4-NO 2 D-1471 NHCH 2 CF 3 NHOH Me 4-NO 2 D-1422 NHEt NHOMe Me 4-NO 2 D-1472 NHCH 2 CF 3 NHOMe Me 4-NO 2 D-1423 NHEt NHOEt Me 4-NO 2 D-1473 NHCH 2 CF 3 NHOEt Me 4-NO 2 D-1424 NHEt NHNH 2 Me 4-NO 2 D-1474 NHCH 2 CF 3 NHNH 2 Me 4-NO 2 D-1425 NHEt NHNMe 2 Me 4-NO 2 D-1475 NHCH 2 CF 3 NHNMe 2 Me 4-NO 2 D-1426 NHEt NHNHMe Me 4-NO 2 D-1476 NHCH 2 CF 3 NHNHMe Me 4-NO 2 D-1427 NHEt NHNHEt Me 4-NO 2 D-1477 NHCH 2 CF 3 NHNHEt Me 4-NO 2 D-1428 NHEt NMeNH 2 Me 4-NO 2 D-1478 NHCH 2 CF 3 NMeNH 2 Me 4-NO 2 D-1429 NHEt NHCN Me 4-NO 2 D-1479 NHCH 2 CF 3 NHCN Me 4-NO 2 D-1430 NHEt NHNO 2 Me 4-NO 2 D-1430 NHCH 2 CF 3 NHNO 2 Me 4-NO 2 D-1431 NH-i-Pr NHOH Me 4-NO 2 D-1481 SMe NHOH Me 4-NO 2 D-1432 NH-i-Pr NHOMe Me 4-NO 2 D-1482 SMe NHOMe Me 4-NO 2 D-1433 NH-i-Pr NHOEt Me 4-NO 2 D-1483 SMe NHOEt Me 4-NO 2 D-1434 NH-i-Pr NHNH 2 Me 4-NO 2 D-1484 SMe NHNH 2 Me 4-NO 2 D-1435 NH-i-Pr NHNMe 2 Me 4-NO 2 D-1485 SMe NHNMe 2 Me 4-NO 2 D-1436 NH-i-Pr NHNHMe Me 4-NO 2 D-1486 SMe NHNHMe Me 4-NO 2 D-1437 NH-i-Pr NHNHEt Me 4-NO 2 D-1487 SMe NHNHEt Me 4-NO 2 D-1438 NH-i-Pr NMeNH 2 Me 4-NO 2 D-1488 SMe NMeNH 2 Me 4-NO 2 D-1439 NH-i-Pr NHCN Me 4-NO 2 D-1489 SMe NHCN Me 4-NO 2 D-1440 NH-i-Pr NHNO 2 Me 4-NO 2 D-1490 SMe NHNO 2 Me 4-NO 2 D-1441 NH-allyl NHOH Me 4-NO 2 D-1491 SEt NHOH Me 4-NO 2 D-1442 NH-allyl NHOMe Me 4-NO 2 D-1492 SEt NHOMe Me 4-NO 2 D-1443 NH-allyl NHOEt Me 4-NO 2 D-1493 SEt NHOEt Me 4-NO 2 D-1444 NH-allyl NHNH 2 Me 4-NO 2 D-1494 SEt NHNH 2 Me 4-NO 2 D-1445 NH-allyl NHNMe 2 Me 4-NO 2 D-1495 SEt NHNMe 2 Me 4-NO 2 D-1446 NH-allyl NHNHMe Me 4-NO 2 D-1496 SEt NHNHMe Me 4-NO 2 D-1447 NH-allyl NHNHEt Me 4-NO 2 D-1497 SEt NHNHEt Me 4-NO 2 D-1448 NH-allyl NMeNH 2 Me 4-NO 2 D-1498 SEt NMeNH 2 Me 4-NO 2 D-1449 NH-allyl NHCN Me 4-NO 2 D-1499 SEt NHCN Me 4-NO 2 D-1450 NH-allyl NHNO 2 Me 4-NO 2 D-1500 SEt NHNO 2 Me 4-NO 2 Compound No. R 15 R 16 R 17 R 18 Compound No. R 15 R 16 R 17 R 18 D-1501 NH 2 NHOH H 4-NH 2 D-1551 NH-propargyl NHOH H 4-NH 2 D-1502 NH 2 NHOMe H 4-NH 2 D-1552 NH-propargyl NHOMe H 4-NH 2 D-1503 NH 2 NHOEt H 4-NH 2 D-1553 NH-propargyl NHOEt H 4-NH 2 D-1504 NH 2 NHNH 2 H 4-NH 2 D-1554 NH-propargyl NHNH 2 H 4-NH 2 D-1505 NH 2 NHNMe 2 H 4-NH 2 D-1555 NH-propargyl NHNMe 2 H 4-NH 2 D-1506 NH 2 NHNHMe H 4-NH 2 D-1556 NH-propargyl NHNHMe H 4-NH 2 D-1507 NH 2 NHNHEt H 4-NH 2 D-1557 NH-propargyl NHNHEt H 4-NH 2 D-1508 NH 2 NMeNH 2 H 4-NH 2 D-1558 NH-propargyl NMeNH 2 H 4-NH 2 D-1509 NH 2 NHCN H 4-NH 2 D-1559 NH-propargyl NHCN H 4-NH 2 D-1510 NH 2 NHNO 2 H 4-NH 2 D-1560 NH-propargyl NHNO 2 H 4-NH 2 D-1511 NHMe NHOH H 4-NH 2 D-1561 NHCH 2 CH 2 F NHOH H 4-NH 2 D-1512 NHMe NHOMe H 4-NH 2 D-1562 NHCH 2 CH 2 F NHOMe H 4-NH 2 D-1513 NHMe NHOEt H 4-NH 2 D-1563 NHCH 2 CH 2 F NHOEt H 4-NH 2 D-1514 NHMe NHNH 2 H 4-NH 2 D-1564 NHCH 2 CH 2 F NHNH 2 H 4-NH 2 D-1515 NHMe NHNMe 2 H 4-NH 2 D-1565 NHCH 2 CH 2 F NHNMe 2 H 4-NH 2 D-1516 NHMe NHNHMe H 4-NH 2 D-1566 NHCH 2 CH 2 F NHNHMe H 4-NH 2 D-1517 NHMe NHNHEt H 4-NH 2 D-1567 NHCH 2 CH 2 F NHNHEt H 4-NH 2 D-1518 NHMe NMeNH 2 H 4-NH 2 D-1568 NHCH 2 CH 2 F NMeNH 2 H 4-NH 2 D-1519 NHMe NHCN H 4-NH 2 D-1569 NHCH 2 CH 2 F NHCN H 4-NH 2 D-1520 NHMe NHNO 2 H 4-NH 2 D-1570 NHCH 2 CH 2 F NHNO 2 H 4-NH 2 D-1521 NHEt NHOH H 4-NH 2 D-1571 NHCH 2 CF 3 NHOH H 4-NH 2 D-1522 NHEt NHOMe H 4-NH 2 D-1572 NHCH 2 CF 3 NHOMe H 4-NH 2 D-1523 NHEt NHOEt H 4-NH 2 D-1573 NHCH 2 CF 3 NHOEt H 4-NH 2 D-1524 NHEt NHNH 2 H 4-NH 2 D-1574 NHCH 2 CF 3 NHNH 2 H 4-NH 2 D-1525 NHEt NHNMe 2 H 4-NH 2 D-1575 NHCH 2 CF 3 NHNMe 2 H 4-NH 2 D-1526 NHEt NHNHMe H 4-NH 2 D-1576 NHCH 2 CF 3 NHNHMe H 4-NH 2 D-1527 NHEt NHNHEt H 4-NH 2 D-1577 NHCH 2 CF 3 NHNHEt H 4-NH 2 D-1528 NHEt NMeNH 2 H 4-NH 2 D-1578 NHCH 2 CF 3 NMeNH 2 H 4-NH 2 D-1529 NHEt NHCN H 4-NH 2 D-1579 NHCH 2 CF 3 NHCN H 4-NH 2 D-1530 NHEt NHNO 2 H 4-NH 2 D-1580 NHCH 2 CF 3 NHNO 2 H 4-NH 2 D-1531 NH-i-Pr NHOH H 4-NH 2 D-1581 SMe NHOH H 4-NH 2 D-1532 NH-i-Pr NHOMe H 4-NH 2 D-1582 SMe NHOMe H 4-NH 2 D-1533 NH-i.Pr NHOEt H 4-NH 2 D-1583 SMe NHOEt H 4-NH 2 D-1534 NH-i-Pr NHNH 2 H 4-NH 2 D-1584 SMe NHNH 2 H 4-NH 2 D-1535 NH-i-Pr NHNMe 2 H 4-NN 2 D-1585 SMe NHNMe 2 H 4-NH 2 D-1536 NH-i-Pr NHNHMe H 4-NH 2 D-1586 SMe NHNHMe H 4-NH 2 D-1537 NH-i-Pr NHNHEt H 4-NH 2 D-1587 SMe NHNHEt H 4-NH 2 D-1538 NH-i-Pr NMeNH 2 H 4-NH 2 D-1588 SMe NMeNH 2 H 4-NH 2 D-1539 NH-i-Pr NHCN H 4-NH 2 D-1589 SMe NHCN H 4-NH 2 D-1540 NH-i-Pr NHNO 2 H 4-NH 2 D-1590 SMe NHNO 2 H 4-NH 2 D-1541 NH-allyl NHOH H 4-NH 2 D.1591 SEt NHOH H 4-NH 2 D-1542 NH-allyl NHOMe H 4-NH 2 D-1592 SEt NHOMe H 4-NH 2 D-1543 NH-allyl NHOEt H 4-NH 2 D-1593 SEt NHOEt H 4-NH 2 D-1544 NH-allyl NHNH 2 H 4-NH 2 D-1594 SEt NHNH 2 H 4-NH 2 D-1545 NH-allyl NHNMe 2 H 4-NH 2 D-1595 SEt NHNMe 2 H 4-NH 2 D-1546 NH-allyl NHNHMe H 4-NH 2 D-1596 SEt NHNHMe H 4-NH 2 D-1547 NH-allyl NHNHEt H 4-NH 2 D-1597 SEt NHNHEt H 4-NH 2 D-1548 NH-allyl NMeNH 2 H 4-NH 2 D-1598 SEt NMeNH 2 H 4-NH 2 D-1549 NH-allyl NHCN H 4-NH 2 D-1599 SEt NHCN H 4-NH 2 D-1550 NH-allyl NHNO 2 H 4-NH 2 D-1600 SEt NHNO 2 H 4-NH 2 Compound No. R 15 R 16 R 17 R 18 Compound No. R 15 R 16 R 17 R 18 D-1601 NH 2 NHOH H 4-NO 2 D-1651 NH-propargyl NHOH H 4-NO 2 D-1602 NH 2 NHOMe H 4-NO 2 D-1652 NH-propargyl NHOMe H 4-NO 2 D-1603 NH 2 NHOEt H 4-NO 2 D-1653 NH-propargyl NHOEt H 4-NO 2 D-1604 NH 2 NHNH 2 H 4-NO 2 D-1654 NH-propargyl NHNH 2 H 4-NO 2 D-1605 NH 2 NHNMe 2 H 4-NO 2 D-1655 NH-propargyl NHNMe 2 H 4-NO 2 D-1606 NH 2 NHNHMe H 4-NO 2 D-1656 NH-propargyl NHNHMe H 4-NO 2 D-1607 NH 2 NHNHEt H 4-NO 2 D-1657 NH-propargyl NHNHEt H 4-NO 2 D-1608 NH 2 NMeNH 2 H 4-NO 2 D-1658 NH-propargyl NMeNH 2 H 4-NO 2 D-1609 NH 2 NHCN H 4-NO 2 D-1659 NH-propargyl NHCN H 4-NO 2 D-1610 NH 2 NHNO 2 H 4-NO 2 D-1660 NH-propargyl NHNO 2 H 4-NO 2 D-1611 NHMe NHOH H 4-NO 2 D-1661 NHCH 2 CH 2 F NHOH H 4-NO 2 D-1612 NHMe NHOMe H 4-Cl D-1662 NHCH 2 CH 2 F NHOMe H 4-NO 2 D-1613 NHMe NHOEt H 4-NO 2 D-1663 NHCH 2 CH 2 F NHOEt H 4-NO 2 D-1614 NHMe NHNH 2 H 4-NO 2 D-1664 NHCH 2 CH 2 F NHNH 2 H 4-NO 2 D-1615 NHMe NHNMe 2 H 4-NO 2 D-1665 NHCH 2 CH 2 F NHNMe 2 H 4-NO 2 D-1616 NHMe NHNHMe H 4-NO 2 D-1666 NHCH 2 CH 2 F NHNHMe H 4-NO 2 D-1617 NHMe NHNHEt H 4-NO 2 D-1667 NHCH 2 CH 2 F NHNHEt H 4-NO 2 D-1618 NHMe NMeNH 2 H 4-NO 2 D-1668 NHCH 2 CH 2 F NMeNH 2 H 4-NO 2 D-1619 NHMe NHCN H 4-NO 2 D-1669 NHCH 2 CH 2 F NHCN H 4-NO 2 D-1620 NHMe NHNO 2 H 4-NO 2 D-1670 NHCH 2 CH 2 F NHNO 2 H 4-NO 2 D-1621 NHEt NHOH H 4-NO 2 D-1671 NHCH 2 CF 3 NHOH H 4-NO 2 D-1622 NHEt NHOMe H 4-NO 2 D-1672 NHCH 2 CF 3 NHOMe H 4-NO 2 D-1623 NHEt NHOEt H 4-NO 2 D-1673 NHCH 2 CF 3 NHOEt H 4-NO 2 D-1624 NHEt NHNH 2 H 4-NO 2 D-1674 NHCH 2 CF 3 NHNH 2 H 4-NO 2 D-1625 NHEt NHNMe 2 H 4-NO 2 D-1675 NHCH 2 CF 3 NHNMe 2 H 4-NO 2 D-1626 NHEt NHNHMe H 4-NO 2 D-1676 NHCH 2 CF 3 NHNHMe H 4-NO 2 D-1627 NHEt NHNHEt H 4-NO 2 D-1677 NHCH 2 CF 3 NHNHEt H 4-NO 2 D-1628 NHEt NMeNH 2 H 4-NO 2 D-1678 NHCH 2 CF 3 NMeNH 2 H 4-NO 2 D-1629 NHEt NHCN H 4-NO 2 D-1679 NHCH 2 CF 3 NHCN H 4-NO 2 D-1630 NHEt NHNO 2 H 4-NO 2 D-1680 NHCH 2 CF 3 NHNO 2 H 4-NO 2 D-1631 NH-i-Pr NHOH H 4-NO 2 D-1681 SMe NHOH H 4-NO 2 D-1632 NH-i-Pr NHOMe H 4-NO 2 D-1682 SMe NHOMe H 4-NO 2 D-1633 NH-i-Pr NHOEt H 4-NO 2 D-1683 SMe NHOEt H 4-NO 2 D-1634 NH-i-Pr NHNH 2 H 4-NO 2 D-1684 SMe NHNH 2 H 4-NO 2 D-1635 NH-i-Pr NHNMe 2 H 4-NO 2 D-1685 SMe NHNMe 2 H 4-NO 2 D-1636 NH-i-Pr NHNHMe H 4-NO 2 D-1686 SMe NHNHMe H 4-NO 2 D-1637 NH-i-Pr NHNHEt H 4-NO 2 D-1687 SMe NHNHEt H 4-NO 2 D-1638 NH-i-Pr NMeNH 2 H 4-NO 2 D-1688 SMe NMeNH 2 H 4-NO 2 D-1639 NH-i-Pr NHCN H 4-NO 2 D-1689 SMe NHCN H 4-NO 2 D-1640 NH-i-Pr NHNO 2 H 4-NO 2 D-1690 SMe NHNO 2 H 4-NO 2 D-1641 NH-allyl NHOH H 4-NO 2 -D-1691 SEt NHOH H 4-NO 2 D-1642 NH-allyl NHOMe H 4-NO 2 D-1692 SEt NHOMe H 4-NO 2 D-1643 NH-allyl NHOEt H 4-NO 2 D-1693 SEt NHOEt H 4-NO 2 D-1644 NH-allyl NHNH 2 H 4-NO 2 D-1694 SEt NHNH 2 H 4-NO 2 D-1645 NH-allyl NHNme 2 H 4-NO 2 D-1695 SEt NHNMe 2 H 4-NO 2 D-1646 NH-allyl NHNHMe H 4-NO 2 D-1696 SEt NHNHMe H 4-NO 2 D-1647 NH-allyl NHNHEt H 4-NO 2 D-1697 SEt NHNHEt H 4-NO 2 D-1648 NH-allyl NMeNH 2 H 4-NO 2 D-1698 SEt NMeNH 2 H 4-NO 2 D-1649 NH-allyl NHCN H 4-NO 2 D-1699 SEt NHCN H 4-NO 2 D-1650 NH-allyl NHNO 2 H 4-NO 2 D-1700 SEt NHNO 2 H 4-NO 2 Compound No. R 15 R 16 R 17 R 18 Compound No. R 15 R 16 R 17 R 18 E-1 S(CH 2 ) 3 NH- H 4-NO 2 E-31 -O(CH 2 ) 3 NH- H 4-NO 2 E-2 -S(CH 2 ) 3 NH- H 4-NH 2 E-32 -O(CH 2 ) 3 NH- H 4-NH 2 E-3 -S(CH 2 ) 3 NH- H 4-Cl E-33 -O(CH 2 ) 3 NH- H 4-Cl E-4 -S(CH 2 ) 3 NH- H 4-OMe E-34 -O(CH 2 ) 3 NH- H 4-OMe E-5 -S(CH 2 ) 3 NH- H 4-Me E-35 -O(CH 2 ) 3 NH- H 4-Me E-6 -S(CH 2 ) 3 NH- Me 2-NH 2 E-36 -O(CH 2 ) 3 NH- Me 4-NO 2 E-7 -S(CH 2 ) 3 NH- Me 4-NH 2 E-37 -O(OH 2 ) 3 NH- Me 4-NH 2 E-8 -S(CH 2 ) 3 NH- Me 4-Cl E-38 -O(CH 2 ) 3 NH- Me 4-Cl E-9 -S(CH 2 ) 3 NH- Me 4-OMe F-39 -O(CH 2 ) 3 NH- Me 4-OMe E-10 -S(CH 2 ) 3 NH- Me 4-Me E-40 -O(CH 2 ) 3 NH- Me 4-Me E-11 -S(CH 2 ) 3 NH- Et 4-NO 2 E-41 -O(CH 2 ) 3 NH- Et 4-NO 2 E-12 -S(CH 2 ) 3 NH- Et 4-NH 2 E-42 -O(CH 2 ) 3 NH- Et 4-NH 2 E-13 -S(CH 2 ) 3 NH- Et 4-Cl E-43 -O(CH 2 ) 3 NH- Et 4-Cl E-14 -S(CH 2 ) 3 NH- Et 4-OMe E-44 -O(CH 2 ) 3 NH- Et 4-OMe E-15 -S(CH 2 ) 3 NH- Et 4-Me E-45 -O(CH 2 ) 3 NH- Et 4-Me E-16 -S(CH 2 ) 2 NH- H 4-NO 2 E-46 -O(CH 2 ) 2 NH- H 4-NO 2 E-17 -S(CH 2 ) 2 NH- H 4-NO 2 E-47 -O(CH 2 ) 2 NH- H 4-NH 2 E-18 -S(CH 2 ) 2 NH- H 4-Cl E-48 -O(CH 2 ) 2 NH- G 4-Cl E-19 -S(CH 2 ) 2 NH- H 4-OMe E-49 -O(CH 2 ) 2 NH- H 4-OMe E-20 -S(CH 2 ) 2 NH- H 4-Me E-50 -O(CH 2 ) 2 NH- H 4-Me E-21 -S(CH 2 ) 2 NH- Me 2-NH 2 E-51 -O(CH 2 ) 2 NH- Me 4-NO 2 E-22 -S(CH 2 ) 2 NH- Me 4-NH 2 E-52 -O(CH 2 ) 2 NH- Me 4-NH 2 E-23 -S(CH 2 ) 2 NH- Me 4-Cl E-53 -O(CH 2 ) 2 NH- Me 4-Cl E-24 -S(CH 2 ) 2 NH- Me 4-OMe E-54 -O(CH 2 ) 2 NH- Me 4-OMe E-25 -S(CH 2 ) 2 NH- Me 4-Me E-55 -O(CH 2 ) 2 NH- Me 4-Me E-26 -S(CH 2 ) 2 NH- Et 4-NO 2 E-56 -O(CH 2 ) 2 NH- Et 4-NO 2 E-27 -S(CH 2 ) 2 NH- Et 4-NH 2 E-57 -O(CH 2 ) 2 NH- Et 4-NH 2 E-28 -S(CH 2 ) 2 NH- Et 4-Cl E-58 -O(CH 2 ) 2 NH- Et 4-Cl E-29 -S(CH 2 ) 2 NH- Et 4-OMe E-59 -O(CH 2 ) 2 NH- Et 4-OMe E-30 -S(CH 2 ) 2 NH- Et 4-Me E-60 -O(CH 2 ) 2 NH- Et 4-Me Compounds F-1 to F-800 shown in Tablse 25 to Table 32 are able to synthesize in a manner similar to those described in Example 22 or Example 23. Table 25 to Table 32 Compound No. R 15 R 16 R 17 R 18 Compound No. R 15 R 16 R 17 R 18 F-1 NH 2 SH H 4-NH 2 F-51 NH-allyl SH H 4-NH 2 F-2 NH 2 SMe H 4-NH 2 F-52 NH-allyl SMe H 4-NH 2 F-3 NH 2 SEt H 4-NH 2 F-53 NH-allyl SEt H 4-NH 2 F-4 NH 2 S-n-Pr H 4-NH 2 F-54 NH-allyl S-n-Pr H 4-NH 2 F-5 NH 2 S-i-Pr H 4-NH 2 F-55 NH-allyl S-i-Pr H 4-NH 2 F-6 NH 2 S-n-Bu H 4-NH 2 F-56 NH-allyl S-n-Bu H 4-NH 2 F-7 NH 2 S-allyl H 4-NH 2 F-57 NH-allyl S-allyl H 4-NH 2 F-8 NH 2 S-propargyl H 4-NH 2 F-58 NH-allyl S-propargyl H 4-NH 2 F-9 NH 2 SCH 2 CF 3 H 4-NH 2 F-59 NH-allyl SCH 2 CF 3 H 4-NH 2 F-10 NH 2 SCH 2 CH 2 F H 4-NH 2 F-60 NH-allyl SCH 2 CH 2 F H 4-NH 2 F-11 NHMe SH H 4-NH 2 F-61 NH-propargyl SH H 4-NH 2 F-12 NHMe SMe H 4-NH 2 F-62 NH-propargyl SMe H 4-NH 2 F-13 NHMe SEt H 4-NH 2 F-63 NH-propargyl SEt H 4-NH 2 F-14 NHMe S-n-Pr H 4-NH 2 F-64 NH-propargyl S-n-Pr H 4-NH 2 F-15 NHMe S-i-Pr H 4-NH 2 F-65 NH-propargyl S-i-Pr H 4-NH 2 F-16 NHMe S-n-Bu H 4-NH 2 F-66 NH-propargyl S-n-Bu H 4-NH 2 F-17 NHMe S-allyl H 4-NH 2 F-67 NH-propargyl S-allyl H 4-NH 2 F-18 NHMe S-propargyl H 4-NH 2 F-68 NH-propargyl S-propargvl H 4-NH 2 F-19 NHMe SCH 2 CF 3 H 4-NH 2 F-69 NH-propargyl SCH 2 CF 3 H 4-NH 2 F-20 NHMe SCH 2 CH 2 F H 4-NH 2 F-70 NH-propargyl SCH 2 CH 2 F H 4-NH 2 F-21 NHEt SH H 4-NH 2 F-71 NHCH 2 CF 3 SH H 4-NH 2 F-22 NHEt SMe H 4-NH 2 F-72 NHCH 2 CF 3 SMe H 4-NH 2 F-23 NHEt SEt H 4-NH 2 F-73 NHCH 2 CF 3 SEt H 4-NH 2 F-24 NHEt S-n-Pr H 4-NH 2 F-74 NHCH 2 CF 3 S-n-Pr H 4-NH 2 F-25 NHEt S-i-Pr H 4-NH 2 F-75 NHCH 2 CF 3 S-i-Pr H 4-NH 2 F-26 NHEt S-n-Bu H 4-NH 2 F-76 NHCH 2 CF 3 S-n-Bu H 4-NH 2 F-27 NHEt S-allyl H 4-NH 2 F-77 NHCH 2 CF 3 S-allyl H 4-NH 2 F-28 NHEt S-propargyl H 4-NH 2 F-78 NHCH 2 CF 3 S-propargyl H 4-NH 2 F-29 NHEt SCH 2 CF 3 H 4-NH 2 F-79 NHCH 2 CF 3 SCH 2 CF 3 H 4-NH 2 F-30 NHEt SCH 2 CH 2 F H 4-NH 2 F-80 NHCH 2 CF 3 SCH 2 CH 2 F H 4-NH 2 F-31 NHPr SH H 4-NH 2 F-81 NHCH 2 CH 2 F SH H 4-NH 2 F-32 NHPr SMe H 4-NH 2 F-82 NHCH 2 CH 2 F SMe H 4-NH 2 F-33 NHPr SEt H 4-NH 2 F-83 NHCH 2 CH 2 F SEt H 4-NH 2 F-34 NHPr S-n-Pr H 4-NH 2 F-84 NHCH 2 CH 2 F S-n-Pr H 4-NH 2 F-35 NHPr S-i-Pr H 4-NH 2 F-85 NHCH 2 CH 2 F S-i-Pr H 4-NH 2 F-36 NHPr S-n-Bu H 4-NH 2 F-86 NHCH 2 CH 2 F S-n-Bu H 4-NH 2 F-37 NHPr S-allyl H 4-NH 2 F-87 NHCH 2 CH 2 F S-allyl H 4-NH 2 F-38 NHPr S-propargyl H 4-NH 2 F-88 NHCH 2 CH 2 F S-propargyl H 4-NH 2 F-39 NHPr SCH 2 CF 3 H 4-NH 2 F-89 NHCH 2 CH 2 F SCH 2 CF 3 H 4-NH 2 F-40 NHPr SCH 2 CH 2 F H 4-NH 2 F-90 NHCH 2 CH 2 F SCH 2 CH 2 F H 4-NH 2 F-41 NH-i-Pr SH H 4-NH 2 F-91 NH-n-Bu SH H 4-NH 2 F-42 NH-i-Pr SMe H 4-NH 2 F-92 NH-n-Bu SMe H 4-NH 2 F-43 NH-i-Pr SEt H 4-NH 2 F-93 NH-n-Bu SEt H 4-NH 2 F-44 NH-i-Pr S-n-Pr H 4-NH 2 F-94 NH-n-Bu S-n-Pr H 4-NH 2 F-45 NH-i-Pr S-i-Pr H 4-NH 2 F-95 NH-n-Bu S-i-Pr H 4-NH 2 F-46 NH-i-Pr S-n-Bu H 4-NH 2 F-96 NH-n-Bu S-n-Bu H 4-NH 2 F-47 NH-i-Pr S-allyl H 4-NH 2 F-97 NH-n-Bu S-allyl H 4-NH 2 F-48 NH-i-Pr S-propargyl H 4-NH 2 F-98 NH-n-Bu S-propargyl H 4-NH 2 F-49 NH-i-Pr SCH 2 CF 3 H 4-NH 2 F-99 NH-n-Bu SCH 2 CF 3 H 4-NH 2 F-50 NH-i-Pr SCH 2 CH 2 F H 4-NH 2 F-100 NH-n-Bu SCH 2 CH 2 F H 4-NH 2 Compound No. R 15 R 16 R 17 R 18 Compound No. R 15 R 16 R 17 R 18 F-101 NH 2 SH H 4-NO 2 F-151 NH-allyl SH H 4-NO 2 F-102 NH 2 SMe H 4-NO 2 F-152 NH-allyl SMe H 4-NO 2 F-103 NH 2 SEt H 4-NO 2 F-153 NH-allyl SEt H 4-NO 2 F-104 NH 2 S-n-Pr H 4-NO 2 F-154 NH-allyl S-n-Pr H 4-NO 2 F-105 NH 2 S-i-Pr H 4-NO 2 F-155 NH-allyl S-i-Pr H 4-NO 2 F-106 NH 2 S-n-Bu H 4-NO 2 F-156 NH-allyl S-n-Bu H 4-NO 2 F-107 NH 2 S-allyl H 4-NO 2 F-157 NH-allyl S-allyl H 4-NO 2 F-108 NH 2 S-propargyl H 4-NO 2 F-158 NH-allyl S-propargyl H 4-NO 2 F-109 NH 2 SCH 2 CF 3 H 4-NO 2 F-159 NH-allyl SCH 2 CF 3 H 4-NO 2 F-110 NH 2 SCH 2 CH 2 F H 4-NO 2 F-160 NH-allyl SCH 2 CH 2 F H 4-NO 2 F-111 NHMe SH H 4-NO 2 F-161 NH-propargyl SH H 4-NO 2 F-112 NHMe SMe H 4-NO 2 F-162 NH-propargyl SMe H 4-NO 2 F-113 NHMe SEt H 4-NO 2 F-163 NH-propargyl SEt H 4-NO 2 F-114 NHMe S-n-Pr H 4-NO 2 F-164 NH-propargyl S-n-Pr H 4-NO 2 F-115 NHMe S-i-Pr H 4-NO 2 F-165 NH-propargyl S-i-Pr H 4-NO 2 F-116 NHMe S-n-Bu H 4-NO 2 F-166 NH-propargyl S-n-Bu H 4-NO 2 F-117 NHMe S-allyl H 4-NO 2 F-167 NH-propargyl S-allyl H 4-NO 2 F-118 NHMe S-propargyl H 4-NO 2 F-168 NH-propargyl S-propargyl H 4-NO 2 F-119 NHMe SCH 2 CF 3 H 4-NO 2 F-169 NH-propargyl SCH 2 CF 3 H 4-NO 2 F-120 NHMe SCH 2 CH 2 F H 4-NO 2 F-170 NH-propargyl SCH 2 CH 2 F H 4-NO 2 F-121 NHEt SH H 4-NO 2 F-171 NHCH 2 CF 3 SH H 4-NO 2 F-122 NHEt SMe H 4-NO 2 F-172 NHCH 2 CF 3 SMe H 4-NO 2 F-123 NHEt SEt H 4-NO 2 F-173 NHCH 2 CF 3 SEt H 4-NO 2 F-124 NHEt S-n-Pr H 4-NO 2 F-174 NHCH 2 CF 3 S-n-Pr H 4-NO 2 F-125 NHEt S-i-Pr H 4-NO 2 F-175 NHCH 2 CF 3 S-i-Pr H 4-NO 2 F-126 NHEt S-n-Bu H 4-NO 2 F-176 NHCH 2 CF 3 S-n-Bu H 4-NO 2 F-127 NHEt S-allyl H 4-NO 2 F-177 NHCH 2 CF 3 S-allyl H 4-NO 2 F-128 NHEt S-propargyl H 4-NO 2 F-178 NHCH 2 CF 3 S-propargyl H 4-NO 2 F-129 NHEt SCH 2 CF 3 H 4-NO 2 F-179 NHCH 2 CF 3 SCH 2 CF 3 H 4-NO 2 F-130 NHEt SCH 2 CH 2 F H 4-NO 2 F-180 NHCH 2 CF 3 SCH 2 CH 2 F H 4-NO 2 F-131 NHPr SH H 4-NO 2 F-181 NHCH 2 CH 2 F SH H 4-NO 2 F-132 NHPr SMe H 4-NO 2 F-182 NHCH 2 CH 2 F SMe H 4-NO 2 F-133 NHPr SEt H 4-NO 2 F-183 NHCH 2 CH 2 F SEt H 4-NO 2 F-134 NHPr S-n-Pr H 4-NO 2 F-184 NHCH 2 CH 2 F S-n-Pr H 4-NO 2 F-135 NHPr S-i-Pr H 4-NO 2 F-185 NHCH 2 CH 2 F S-i-Pr H 4-NO 2 F-136 NHPr S-n-Bu H 4-NO 2 F-186 NHCH 2 CH 2 F S-n-Bu H 4-NO 2 F-137 NHPr S-allyl H 4-NO 2 F-187 NHCH 2 CH 2 F S-allyl H 4-NO 2 F-138 NHPr S-propargyl H 4-NO 2 F-188 NHCH 2 CH 2 F S-propargyl H 4-NO 2 F-139 NHPr SCH 2 CF 3 H 4-NO 2 F-189 NHCH 2 CH 2 F SCH 2 CF 3 H 4-NO 2 F-140 NHPr SCH 2 CH 2 F H 4-NO 2 F-190 NHOH 2 CH 2 F SCH 2 CH 2 F H 4-NO 2 F-141 NH-i-Pr SH H 4-NO 2 F-191 NH-n-Bu SH H 4-NO 2 F-142 NH-i-Pr SMe H 4-NO 2 F-192 NH-n-Bu SMe H 4-NO 2 F-143 NH-i-Pr SEt H 4-NO 2 F-193 NH-n-Bu SEt H 4-NO 2 F-144 NH-i-Pr S-n-Pr H 4-NO 2 F-194 NH-n-Bu S-n-Pr H 4-NO 2 F-145 NH-i-Pr S-i-Pr H 4-NO 2 F-195 NH-n-Bu S-i-Pr H 4-NO 2 F-146 NH-i-Pr S-n-Bu H 4-NO 2 F-196 NH-n-Bu S-n-Bu H 4-NO 2 F-147 NH-i-Pr S-allyl H 4-NO 2 F-197 NH-n-Bu S-allyl H 4-NO 2 F-148 NH-i-Pr S-propargyl H 4-NO 2 F-198 NH-n-Bu S-propargyl H 4-NO 2 F-149 NH-i-Pr SCH 2 CF 3 H 4-NO 2 F-199 NH-n-Bu SCH 2 CF 3 H 4-NO 2 F-150 NH-i-Pr SCH 2 CH 2 F H 4-NO 2 F-200 NH-n-Bu SCH 2 CH 2 F H 4-NO 2 Compound No. R 15 R 16 R 17 R 18 Compound No. R 15 R 16 R 17 R 18 F-201 NH 2 SH Me 4-NH 2 F-251 NH-allyl SH Me 4-NH 2 F-202 NH 2 SMe Me 4-NH 2 F-252 NH-allyl SMe Me 4-NH 2 F-203 NH 2 SEt Me 4-NH 2 F-253 NH-allyl SEt Me 4-NH 2 F-204 NH 2 S-n-Pr Me 4-NH 2 F-254 NH-allyl S-n-Pr Me 4-NH 2 F-205 NH 2 S-i-Pr Me 4-NH 2 F-255 NH-allyl S-i-Pr Me 4-NH 2 F-206 NH 2 S-n-Bu Me 4-NH 2 F-256 NH-allyl S-n-Bu Me 4-NH 2 F-207 NH 2 S-allyl Me 4-NH 2 F-257 NH-allyl S-allyl Me 4-NH 2 F-208 NH 2 S-propargyl Me 4-NH 2 F-258 NH-allyl S-propargyl Me 4-NH 2 F-209 NH 2 SCH 2 CF 3 Me 4-NH 2 F-259 NH-allyl SCH 2 CF 3 Me 4-NH 2 F-210 NH 2 SCH 2 CH 2 F Me 4-NH 2 F-260 NH-allyl SCH 2 CH 2 F Me 4-NH 2 F-211 NHMe SH Me 4-NH 2 F-261 NH-propargyl SH Me 4-NH 2 F-212 NHMe SMe Me 4-NH 2 F-262 NH-propargyl SMe Me 4-NH 2 F-213 NHMe SEt Me 4-NH 2 F-263 NH-propargyl SEt Me 4-NH 2 F-214 NHMe S-n-Pr Me 4-NH 2 F-264 NH-propargyl S-n-Pr Me 4-NH 2 F-215 NHMe S-i-Pr Me 4-NH 2 F-265 NH-propargyl S-i-Pr Me 4-NH 2 F-216 NHMe S-n-Bu Me 4-NH 2 F-266 NH-propargyl S-n-Bu Me 4-NH 2 F-217 NHMe S-allyl Me 4-NH 2 F-267 NH-propargyl S-allyl Me 4-NH 2 F-218 NHMe S-propargyl Me 4-NH 2 F-268 NH-propargyl S-propargyl Me 4-NH 2 F-219 NHMe SCH 2 CF 3 Me 4-NH 2 F-269 NH-propargyl SCH 2 CF 3 Me 4-NH 2 F-220 NHMe SCH 2 CH 2 F Me 4-NH 2 F-270 NH-propargyl SCH 2 CH 2 F Me 4-NH 2 F-221 NHEt SH Me 4-NH 2 F-271 NHCH 2 CF 3 SH Me 4-NH 2 F-222 NHEt SMe Me 4-NH 2 F-272 NHCH 2 CF 3 SMe Me 4-MH 2 F-223 NHEt SEt Me 4-NH 2 F-273 NHCH 2 CF 3 SEt Me 4-NH 2 F-224 NHEt S-n-Pr Me 4-NH 2 F-274 NHCH 2 CF 3 S-n-Pr Me 4-NH 2 F-225 NHEt S-i-Pr Me 4-NH 2 F-275 NHCH 2 CF 3 S-i-Pr Me 4-NH 2 F-226 NHEt S-n-Bu Me 4-NH 2 F-276 NHCH 2 CF 3 S-n-Bu Me 4-NH 2 F-227 NHEt S-allyl Me 4-NH 2 F-277 NHCH 2 CF 3 S-allyl Me 4-NH 2 F-228 NHEt S-propargyl Me 4-NH 2 F-278 NHOH 2 CF 3 S-propargyl Me 4-NH 2 F-229 NHEt SCH 2 CF 3 Me 4-NH 2 F-279 NHCH 2 CF 3 SCH 2 CF 3 Me 4-NH 2 F-230 NHEt SCH 2 CH 2 F Me 4-NH 2 F-280 NHCH 2 CF 3 SCH 2 CH 2 F Me 4-NH 2 F-231 NHPr SH Me 4-NH 2 F-281 NHCH 2 CH 2 F SH Me 4-NH 2 F-232 NHPr SMe Me 4-NH 2 F-282 NHCH 2 CH 2 F SMe Me 4-NH 2 F-233 NHPr SEt Me 4-NH 2 F-283 NHCH 2 CH 2 F SEt Me 4-NH 2 F-234 NHPr S-n-Pr Me 4-NH 2 F-284 NHCH 2 CH 2 F S-n-Pr Me 4-NH 2 F-235 NHPr S-i-Pr Me 4-NH 2 F-285 NHCH 2 CH 2 F S-i-Pr Me 4-NH 2 F-236 NHPr S-n-Bu Me 4-NH 2 F-286 NHCH 2 CH 2 F S-n-Bu Me 4-NHz F-237 NHPr S-allyl Me 4-NH 2 F-287 NHCH 2 CH 2 F S-allyl Me 4-NH 2 F-238 NHPr S-propargyl Me 4-NH 2 F-288 NHCH 2 CH 2 S-propargyl Me 4-NH 2 F-239 NHPr SCH 2 CF 3 Me 4-NH 2 F-289 NHCH 2 CH 2 F SCH 2 CF 3 Me 4-NH 2 F-240 NHPr SCH 2 CH 2 F Me 4-NH 2 F-290 NHCH 2 CH 2 F SCH 2 CH 2 F Me 4-NH 2 F-241 NH-i-Pr SH Me 4-NH 2 F-291 NH-n-Bu SH Me 4-NH 2 F-242 NH-i-Pr SMe Me 4-NH 2 F-292 NH-n-Bu SMe Me 4-NH 2 F-243 NH-i-Pr SEt Me 4-NHz F-293 NH-n-Bu SEt Me 4-NH 2 F-244 NH-i-Pr S-n-Pr Me 4-NH 2 F-294 NH-n-Bu S-n-Pr Me 4-NH 2 F-245 NH-i-Pr S-i-Pr Me 4-NH 2 F-295 NH-n-Bu S-i-Pr Me 4-NH 2 F-246 NH-i-Pr S-n-Bu Me 4-NH 2 F-296 NH-n-Bu S-n-Bu Me 4-NH 2 F-247 NH-i-Pr S-allyl Me 4-NH 2 F-297 NH-n-Bu S-allyl Me 4-NH 2 F-248 NH-i-Pr S-propargyl Me 4-NH 2 F-298 NH-n-Bu S-propargyl Me 4-NH 2 F-249 NH-i-Pr SCH 2 CF 3 Me 4-NH 2 F-299 NH-n-Bu SCH 2 CF 3 Me 4-NH 2 F-250 NH-i-Pr SCH 2 CH 2 F Me 4-NH 2 F-300 NH-n-Bu SCH 2 CH 2 F Me 4-NH 2 Compound No. R 15 R 16 R 17 R 18 Compound No. R 15 R 16 R 17 R 18 F-301 NH 2 SH Me 4-NO 2 F-351 NH-allyl SH Me 4-NO 2 F-302 NH 2 SMe Me 4-NO 2 F-352 NH-allyl SMe Me 4-NO 2 F-303 NH 2 SEt Me 4-NO 2 F-353 NH-allyl SEt Me 4-NO 2 F-304 NH 2 S-n-Pr Me 4-NO 2 F-354 NH-allyl S-n-Pr Me 4-NO 2 F-305 NH 2 S-i-Pr Me 4-NO 2 F-355 NH-allyl S-i-Pr Me 4-NO 2 F-306 NH 2 S-n-Bu Me 4-NO 2 F-356 NH-allyl S-n-Bu Me 4-NO 2 F-307 NH 2 S-allyl Me 4-NO 2 F-357 NH-allyl S-allyl Me 4-NO 2 F-308 NH 2 S-propargyl Me 4-NO 2 F-358 NH-allyl S-propargyl Me 4-NO 2 F-309 NH 2 SCH 2 CF 3 Me 4-NO 2 F-359 NH-allyl SCH 2 CF 3 Me 4-NO 2 F-310 NH 2 SCH 2 CH 2 F Me 4-NO 2 F-360 NH-allyl SCH 2 CH 2 F Me 4-NO 2 F-311 NHMe SH Me 4-NO 2 F-361 NH-propargyl SH Me 4-NO 2 F-312 NHMe SMe Me 4-NO 2 F-362 NH-propargyl SMe Me 4-NO 2 F-313 NHMe SEt Me 4-NO 2 F-363 NH-propargyl SEt Me 4-NO 2 F-314 NHMe S-n-Pr Me 4-NO 2 F-364 NH-propargyl S-n-Pr Me 4-NO 2 F-315 NHMe S-i-Pr Me 4-NO 2 F-365 NH-propargyl S-i-Pr Me 4-NO 2 F-316 NHMe S-n-Bu Me 4-NO 2 F-366 NH-propargyl S-n-Bu Me 4-NO 2 F-317 NHMe S-allyl Me 4-NO 2 F-367 NH-propargyl S-allyl Me 4-NO 2 F-318 NHMe S-propargyl Me 4-NO 2 F-368 NH-propargyl S-propargyl Me 4-NO 2 F-319 NHMe SCH 2 CF 3 Me 4-NO 2 F-369 NH-propargyl SCH 2 CF 3 Me 4-NO 2 F-320 NHMe SCH 2 CH 2 F Me 4-NO 2 F-370 NH-propargyl SCH 2 CH 2 F Me 4-NO 2 F-321 NHEt SH Me 4-NO 2 F-371 NHCH 2 CF 3 SH Me 4-NO 2 F-322 NHEt SMe Me 4-OMe F-372 NHCH 2 CF 3 SMe Me 4-NO 2 F-323 NHEt SEt Me 4-Cl F-373 NHCH 2 CF 3 SEt Me 4-NO 2 F-324 NHEt S-n-Pr Me 4-NO 2 F-374 NHCH 2 CF 3 S-n-Pr Me 4-NO 2 F-325 NHEt S-i-Pr Me 4-NO 2 F-375 NHCH 2 CF 3 S-i-Pr Me 4-NO 2 F-326 NHEt S-n-Bu Me 4-NO 2 F-376 NHCH 2 CF 3 S-n-Bu Me 4-NO 2 F-327 NHEt S-allyl Me 4-NO 2 F-377 NHCH 2 CF 3 S-allyl Me 4-NO 2 F-328 NHEt S-propargyl Me 4-NO 2 F-378 NHCH 2 CF 3 S-propargyl Me 4-NO 2 F-329 NHEt SCH 2 CF 3 Me 4-NO 2 F-379 NHCH 2 CF 3 SCH 2 CF 3 Me 4-NO 2 F-330 NHEt SCH 2 CH 2 F Me 4-NO 2 F-380 NHCH 2 CF 3 SCH 2 CH 2 F Me 4-NO 2 F-331 NHPr SH Me 4-NO 2 F-381 NHCH 2 CH 2 F SH Me 4-NO 2 F-332 NHPr SMe Me 4-NO 2 F-382 NHCH 2 CH 2 F SMe Me 4-NO 2 F-333 NHPr SEt Me 4-NO 2 F-383 NHCH 2 CH 2 F SEt Me 4-NO 2 F-334 NHPr S-n-Pr Me 4-NO 2 F-384 NHCH 2 CH 2 F S-n-Pr Me 4-NO 2 F-335 NHPr S-i-Pr Me 4-NO 2 F-385 NHCH 2 CH 2 F S-i-Pr Me 4-NO 2 F-336 NHPr S-n-Bu Me 4-NO 2 F-386 NHCH 2 CH 2 F S-n-Bu Me 4-NO 2 F-337 NHPr S-allyl Me 4-NO 2 F-387 NHCH 2 CH 2 F S-allyl Me 4-NO 2 F-338 NHPr S-propargyl Me 4-NO 2 F-388 NHCH 2 CH 2 F S-propargyl Me 4-NO 2 F-339 NHPr SCH 2 CF 3 Me 4-NO 2 F-389 NHCH 2 CH 2 F SCH 2 CF 3 Me 4-NO 2 F-340 NHPr SCH 2 CH 2 F Me 4-NO 2 F-390 NHCH 2 CH 2 F SCH 2 CH 2 F Me 4-NO 2 F-341 NH-i-Pr SH Me 4-NO 2 F-391 NH-n-Bu SH Me 4-NOz F-342 NH-i-Pr SMe Me 4-NO 2 F-392 NH-n-Bu SMe Me 4-NO 2 F-343 NH-i-Pr SEt Me 4-NO 2 F-393 NH-n-Bu SEt Me 4-NO 2 F-344 NH-i-Pr S-n-Pr Me 4-NO 2 F-394 NH-n-Bu S-n-Pr Me 4-NO 2 F-345 NH-i-Pr S-i-Pr Me 4-NO 2 F-395 NH-n-Bu S-i-Pr Me 4-NO 2 F-346 NH-i-Pr S-n-Bu Me 4-NO 2 F-396 NH-n-Bu S-n-Bu Me 4-NO 2 F-347 NH-i-Pr S-allyl Me 4-NO 2 F-397 NH-n-Bu S-allyl Me 4-NO 2 F-348 NH-i-Pr S-propargyl Me 4-NO 2 F-398 NH-n-Bu S-propargyl Me 4-NO 2 F-349 NH-i-Pr SCH 2 CF 3 Me 4-NO 2 F-399 NH-n-Bu SCH 2 CF 3 Me 4-NO 2 F-350 NH-i-Pr SCH 2 CH 2 F Me 4-NO 2 F-400 NH-n-Bu SCH 2 CH 2 F Me 4-NO 2 Compound No. R 15 R 16 R 17 R 18 Compound No. R 15 R 16 R 17 R 18 F-401 NH 2 NH 2 Me 4-NO 2 F-451 NH-propargyl NHCH 2 CF 3 Me 4-NO 2 F-402 NH 2 NHMe Me 4-NO 2 F-452 NH-propargyl NHCH 2 CH 2 F Me 4-NO 2 F-403 NH 2 NHEt Me 4-NO 2 F-453 NHCH 2 CF 3 NHCH 2 CF 3 Me 4-NO 2 F-404 NH 2 NHPr Me 4-NO 2 F-454 NHCH 2 CF 3 NHCH 2 CH 2 F Me 4-NO 2 F-405 NH 2 NH-i-Pr Me 4-NO 2 F-455 NHCH 2 CH 2 F NHCH 2 CH 2 F Me 4-NO 2 F-406 NH 2 NH-n-Bu Me 4-NO 2 F-456 NHOMe NH 2 Me 4-NO 2 F-407 NH 2 NH-allyl Me 4-NO 2 F-457 NHOMe NHMe Me 4-NO 2 F-408 NH 2 NH-propargyl Me 4-NO 2 F-458 NHOMe NHEt Me 4-NO 2 F-409 NH 2 NHCH 2 CF 3 Me 4-NO 2 F-459 NHOMe NHPr Me 4-NO 2 F-410 NH 2 NHCH 2 CH 2 F Me 4-NO 2 F-460 NHOMe NH-i-Pr Me 4-NO 2 F-411 NHMe NHMe Me 4-NO 2 F-461 NHOMe NH-a-Bu Me 4-NO 2 F-412 NHMe NHEt Me 4-NO 2 F-462 NHOMe NH-allyl Me 4-NO 2 F-413 NHMe NHPr Me 4-NO 2 F-463 NHOMe NH-propargyl Me 4-NO 2 F-414 NHMe NH-i-Pr Me 4-NO 2 F-464 NHOMe NHCH 2 CF 3 Me 4-NO 2 F-415 NHMe NH-n-Bu Me 4-NO 2 F-465 NHOMe NHCH 2 CH 2 F Me 4-NO 2 F-416 NHMe NH-allyl Me 4-NO 2 F-466 NHOEt NH 2 Me 4.NO 2 F-417 NHMe NH-propargyl Me 4-NO 2 F-467 NHOEt NHMe Me 4-NO 2 F-418 NHMe NHCH 2 CF 3 Me 4-NO 2 F-468 NHOEt NHEt Me 4-NO 2 F-419 NHMe NHCH 2 CH 2 F Me 4-NO 2 F-469 NHOEt NHPr Me 4-NO 2 F-420 NHEt NHEt Me 4-Cl F-470 NHOEt NH-i-Pr Me 4-NO 2 F-421 NHEt NHPr Me 4-NO 2 F-471 NHOEt NH-n-Bu Me 4-NO 2 F-422 NHEt NH-i-Pr Me 4-NO 2 F-472 NHOEt NH-allyl Me 4-NO 2 F-423 NHEt NH-n-Bu Me 4-NO 2 F-473 NHOEt NH-propargyl Me 4-NO 2 F-424 NHEt NH-allyl Me 4-NO 2 F-474 NHOEt NHCH 2 CF 3 Me 4-NO 2 F-425 NHEt NH-propargyl Me 4-NO 2 F-475 NHOEt NHCH 2 CH 2 F Me 4-NO 2 F-426 NHEt NHCH 2 CF 3 Me 4-NO 2 F-476 NHNMe 2 NH 2 Me 4-NO 2 F-427 NHEt NHCH 2 CH 2 F Me 4-NO 2 F-477 NHNMe 2 NHMe Me 4-NO 2 F-428 NHPr NHPr Me 4-NO 2 F-478 NHNMe 2 NHEt Me 4-NO 2 F-429 NHPr NH-i-Pr Me 4-NO 2 F-479 NHNMe 2 NHPr Me 4-NO 2 F-430 NHPr NH-n-Bu Me 4-NO 2 F-480 NHNMe 2 NH-i-Pr Me 4-NO 2 F-431 NHPr NH-allyl Me 4-NO 2 F-481 NHNMe 2 NH-n-Bu Me 4-NO 2 F-432 NHPr NH-propargyl Me 4-NO 2 F-482 NHNMe 2 NH-allyl Me 4-NO 2 F-433 NHPr NHCH 2 CF 3 Me 4-NO 2 F-483 NHNMe 2 NH-propargyl Me 4-NO 2 F-434 NHPr NHCH 2 CH 2 F Me 4-NO 2 F-484 NHNMe 2 NHCH 2 CF 3 Me 4-NO 2 F-435 NH-i-Pr NH-i-Pr Me 4-NO 2 F-485 NHNMe 2 NHCH 2 CH 2 F Me 4-NO 2 F-436 NH-i-Pr NH-n-Bu Me 4-NO 2 F-486 NHNH 2 NH 2 Me 4-NO 2 F-437 NH-i-Pr NH-allyl Me 4-NO 2 F-487 NHNH 2 NHMe Me 4-NO 2 F-438 NH-i-Pr NH-propargyl Me 4-NO 2 F-488 NHNH 2 NHEt Me 4-NO 2 F-439 NH-i-Pr NHCH 2 CF 3 Me 4-NO 2 F-489 NHNH 2 NHPr Me 4-NO 2 F-440 NH-i-Pr NHCH 2 CH 2 F Me 4-NO 2 F-490 NHNH 2 NH-i-Pr Me 4-NO 2 F-441 NH-n-Bu NH-n-Bu Me 4-NO 2 F-491 NHNH 2 NH-n-Bu Me 4-NO 2 F-442 NH-n-Bu NH-allyl Me 4-NO 2 F-492 NHNH 2 NH-allyl Me 4-NO 2 F-443 NH-n-Bu NH-propargyl Me 4-NO 2 F-493 NHNH 2 NH-propargyl Me 4-NO 2 F-444 NH-n-Bu NHCH 2 CF 3 Me 4-NO 2 F-494 NHNH 2 NHCH 2 CF 3 Me 4-NO 2 F-445 NH-n-Bu NHCH 2 CH 2 F Me 4-NO 2 F-495 NHNH 2 NHCH 2 CH 2 F Me 4-NO 2 F-446 NH-allyl NH-allyl Me 4-NO 2 F-496 NHNHMe NHMe Me 4-NO 2 F-447 NH-allyl NH-propargyl Me 4-NO 2 F-497 NHNHMe NHEt Me 4-NO 2 F-448 NH-allyl NHCH 2 CF 3 Me 4-NO 2 F-498 NHNHMe NHPr Me 4-NO 2 F-449 NH-allyl NHCH 2 CH 2 F Me 4-NO 2 F-499 NHNHMe NH-i-Pr Me 4-NO 2 F-450 NH-propargyl NH-propargyl Me 4-NO 2 F-500 NHNHMe NHCH 2 CF 3 Me 4-NO 2 Compound No. R 15 R 16 R 17 R 18 Compound No. R 15 R 16 R 17 R 18 F-501 NH 2 NH 2 H 4-NO 2 F-551 NH-propargyl NHCH 2 CF 3 H 4-NO 2 F-502 NH 2 NHMe H 4-NO 2 F-552 NH-propargyl NHCH 2 CH 2 F H 4-NO 2 F-503 NH 2 NHEt H 4-NO 2 F-553 NHCH 2 CF 3 NHCH 2 CF 3 H 4-NO 2 F-504 NH 2 NHPr H 4-NO 2 F-554 NHCH 2 CF 3 NHCH 2 CH 2 F H 4-NO 2 F-505 NH 2 NH-i-Pr H 4-NO 2 F-555 NHCH 2 CH 2 F NHCH 2 CH 2 F H 4-NO 2 F-506 NH 2 NH-n-Bu H 4-NO 2 F-556 NHOMe NH 2 H 4-NO 2 F-507 NH 2 NH-allyl H 4-NO 2 F-557 NHOMe NHMe H 4-NO 2 F-508 NH 2 NH-propargyl H 4-NO 2 F-558 NHOMe NHEt H 4-NO 2 F-509 NH 2 NHCH 2 CF 3 H 4-NO 2 F-559 NHOMe NHPr H 4-NO 2 F-510 NH 2 NHCH 2 CH 2 F H 4-NO 2 F-560 NHOMe NH-i-Pr H 4-NO 2 F-511 NHMe NHMe H 4-NO 2 F-561 NHOMe NH-n-Bu H 4-NO 2 F-512 NHMe NHEt H 4-NO 2 F-562 NHOMe NH-allyl H 4-NO 2 F-513 NHMe NHPr H 4-NO 2 F-563 NHOMe NH-propargyl H 4-NO 2 F-514 NHMe NH-i-Pr H 4-NO 2 F-564 NHOMe NHCH 2 CF 3 H 4-NO 2 F-515 NHMe NH-n-Bu H 4-NO 2 F-565 NHOMe NHCH 2 CH 2 F H 4-NO 2 F-516 NHMe NH-allyl H 4-NO 2 F-566 NHOEt NH 2 H 4-NO 2 F-517 NHMe NH-propargyl H 4-NO 2 F-567 NHOEt NHMe H 4-NO 2 F-518 NHMe NHCH 2 CF 3 H 4-NO 2 F-568 NHOEt NHEt H 4-NO 2 F-519 NHMe NHCH 2 CH 2 F H 4-NO 2 F-569 NHOEt NHPr H 4-NO 2 F-520 NHEt NHEt H 4-NO 2 F-570 NHOEt NH-i-Pr H 4-NO 2 F-521 NHEt NHPr H 4-NO 2 F-571 NHOEt NH-n-Bu H 4-NO 2 F-522 NHEt NH-i-Pr H 4-NO 2 F-572 NHOEt NH-allyl H 4-NO 2 F-523 NHEt NH-n-Bu H 4-NO 2 F-573 NHOEt NH-propargyl H 4-NO 2 F-524 NHEt NH-allyl H 4-NO 2 F-574 NHOEt NHCH 2 CF 3 H 4-NO 2 F-525 NHEt NH-propargyl H 4-NO 2 F-575 NHOEt NHCH 2 CH 2 F H 4-NO 2 F-526 NHEt NHCH 2 CF 3 H 4-NO 2 F-576 NHNMe 2 MH 2 H 4-NO 2 F-527 NHEt NHCH 2 CH 2 F H 4-NO 2 F-577 NHNMe 2 NHMe H 4-NO 2 F-528 NHPr NHPr H 4-NO 2 F-578 NHNMe 2 NHEt H 4-NO 2 F-529 NHPr NH-i-Pr H 4-NO 2 F-579 NHNMe 2 NHPr H 4-NO 2 F-530 NHPr NH-n-Bu H 4-NO 2 F-580 NHNMe 2 NH-i-Pr H 4-NO 2 F-531 NHPr NH-allyl H 4-NO 2 F-581 NHNMe 2 NH-n-Bu H 4-NO 2 F-532 NHPr NH-propargyl H 4-NO 2 F-582 NHNMe 2 NH-allyl H 4-NO 2 F-533 NHPr NHCH 2 CF 3 H 4-NO 2 F-583 NHNMe 2 NH-propargyl H 4-NO 2 F-534 NHPr NHCH 2 CH 2 F H 4-NO 2 F-584 NHNMe 2 NHCH 2 CF 3 H 4-NO 2 F-535 NH-i-Pr NU-i-Pr H 4-NO 2 F-585 NHNMe 2 NHCH 2 CH 2 F H 4-NO 2 F-536 NH-i-Pr NH-n-Bu H 4-NO 2 F-586 NHNH 2 NH 2 H 4-NO 2 F-537 NH-i-Pr NH-allyl H 4-NO 2 F-587 NHNH 2 NHMe H 4-NO 2 F-538 NH-i-Pr NH-propargyl H 4-NO 2 F-588 NHNH 2 NHEt H 4-NO 2 F-539 NH-i-Pr NHCH 2 CF 3 H 4-NO 2 F-589 NHNH 2 NHPr H 4-NO 2 F-540 NH-i-Pr NHCH 2 CH 2 F H 4-NO 2 F-590 NHNH 2 NH-i-Pr H 4-NO 2 F-541 NH-n-Bu NH-n-Bu H 4-NO 2 F-591 NHNH 2 NH-n-Bu H 4-NO 2 F-542 NH-n-Bu NH-allyl H 4-NO 2 F-592 NHNH 2 NH-allyl H 4-NO 2 F-543 NH-n-Bu NH-propargyl H 4-NO 2 F-593 NHNH 2 NH-propargyl H 4-NO 2 F-544 NH-n-Bu NHCH 2 CF 3 H 4-NO 2 F-594 NHNH 2 NHCH 2 CF 3 H 4-NO 2 F-545 NH-n-Bu NHCH 2 CH 2 F H 4-NO 2 F-595 NHNH 2 NHCH 2 CH 2 F H 4-NO 2 F-546 NH-allyl NH-allyl H 4-NO 2 F-596 NHNHMe NHMe H 4-NO 2 F-547 NH-allyl NH-propargyl H 4-NO 2 F-597 NHNHMe NHEt H 4-NO 2 F-548 NH-allyl NHCH 2 CF 3 H 4-NO 2 F-598 NHNHMe NHPr H 4-NO 2 F-549 NH-allyl NHCH 2 CH 2 F H 4-NO 2 F-599 NHNHMe NH-i-Pr H 4-NO 2 F-550 NH-propargyl NH-propargyl H 4-NO 2 F-600 NHNHMe NHCH 2 CF 3 H 4-NO 2 Compound No. R 15 R 16 R 17 R 18 Compound No. R 15 R 16 R 17 R 18 F-601 NH 2 NH 2 Me 4-NH 2 F-651 NH-propargyl NHCH 2 CF 3 Me 4-NH 2 F-602 NH 2 NHMe Me 4-NH 2 F-652 NH-propargyl NHCH 2 CH 2 F Me 4-NH 2 F-603 NH 2 NHEt Me 4-NH 2 F-653 NHCH 2 CF 3 NHCH 2 CF 3 Me 4-NH 2 F-604 NH 2 NHPr Me 4-NH 2 F-654 NHCH 2 CF 3 NHCH 2 CH 2 F Me 4-NH 2 F-605 NH 2 NH-i-Pr Me 4-NH 2 F-655 NHCH 2 CH 2 F NHCH 2 CH 2 F Me 4-NH 2 F-606 NH 2 NH-n-Bu Me 4-NH 2 F-656 NHOMe NH 2 Me 4-NH 2 F-607 NH 2 NH-allyl Me 4-NH 2 F-657 NHOMe NHMe Me 4-NH 2 F-608 NH 2 NH-propargyl Me 4-NH 2 F-658 NHOMe NHEt Me 4-NH 2 F-609 NH 2 NHCH 2 CF 3 Me 4-NH 2 F-659 NHOMe NHPr Me 4-NH 2 F-610 NH 2 NHCH 2 CH 2 F Me 4-NH 2 F-660 NHOMe NH-i-Pr Me 4-NH 2 F-611 NHMe NHMe Me 4-NH 2 F-661 NHOMe NH-n-Bu Me 4-NH 2 F-612 NHMe NHEt Me 4-NH 2 F-662 NHOMe NH-allyl Me 4-NH 2 F-613 NHMe NHPr Me 4-NHz F-663 NHOMe NH-propargyl Me 4-NH 2 F-614 NHMe NH-i-Pr Me 4-NH 2 F-664 NHOMe NHCH 2 CF 3 Me 4-NH 2 F-615 NHMe NH-n-Bu Me 4-NH 2 F-665 NHOMe NHCH 2 CH 2 F Me 4-NH 2 F-616 NHMe NH-allyl Me 4-NH 2 F-666 NHOEt NH 2 Me 4-NH 2 F-617 NHMe NH-propargyl Me 4-NH 2 F-667 NHOEt NHMe Me 4-NH 2 F-618 NHMe NHCH 2 CF 3 Me 4-NH 2 F-668 NHOEt NHEt Me 4-NH 2 F-619 NHMe NHCH 2 CH 2 F Me 4-NH 2 F-669 NHOEt NHPr Me 4-NH 2 F-620 NHEt NHEt Me 4-NH 2 F-670 NHOEt NH-i-Pr Me 4-NH 2 F-621 NHEt NHPr Me 4-NH 2 F-671 NHOEt NH-n-Bu Me 4-NH 2 F-622 NHEt NH-i-Pr Me 4-NH 2 F.672 NHOEt NH-allyl Me 4-NH 2 F-623 NHEt NH-n-Bu Me 4-NH 2 F-673 NHOEt NH-propargyl Me 4-NH 2 F-624 NHEt NH-allyl Me 4-NH 2 F-674 NHOEt NHCH 2 CF 3 Me 4-NH 2 F-625 NHEt NH-propargyl Me 4-NH 2 F-675 NHOEt NHCH 2 CH 2 F Me 4-NH 2 F-626 NHEt NHCH 2 CF 3 Me 4-NH 2 F-676 NHNMe 2 NH 2 Me 4-NH 2 F-627 NHEt NHCH 2 CH 2 F Me 4-NH 2 F-677 NHNMe 2 NHMe Me 4-NH 2 F-628 NHPr NHPr Me 4-NH 2 F-678 NHNMe 2 NHEt Me 4-NH 2 F-629 NHPr NH-i-Pr Me 4-NH 2 F-679 NHNMe 2 NHPr Me 4-NH 2 F-630 NHPr NH-n-Bu Me 4-NH 2 F-680 NHNMe 2 NH-i-Pr Me 4-NH 2 F-631 NHPr NH-allyl Me 4-NH 2 F-681 NHNMe 2 NH-n-Bu Me 4-NH 2 F-632 NHPr NH-propargyl Me 4-NH 2 F-682 NHNMe 2 NH-allyl Me 4-NH 2 F-633 NHPr NHCH 2 CF 3 Me 4-NH 2 F-683 NHNMe 2 NH-propargyl Me 4-NH 2 F-634 NHPr NHCH 2 CH 2 F Me 4-NH 2 F-684 NHNMe 2 NHCH 2 CF 3 Me 4-NH 2 F-635 NH-i-Pr NH-i-Pr Me 4-NH 2 F-685 NHNMe 2 NHCH 2 CH 2 F Me 4-NH 2 F-636 NH-i-Pr NH-n-Bu Me 4-NH 2 F-686 NHNH 2 NH 2 Me 4-NH 2 F-637 NH-i-Pr NH-allyl Me 4-NH 2 F-687 NHNH 2 NHMe Me 4-NH 2 F-638 NH-i-Pr NH-propargyl Me 4-NH 2 F-688 NHNH 2 NHEt Me 4-NH 2 F-639 NH-i-Pr NHCH 2 CF 3 Me 4-NH 2 F-689 NHNH 2 NHPr Me 4-NH 2 F-640 NH-i-Pr NHCH 2 CH 2 F Me 4-NH 2 F-690 NHNH 2 NH-i-Pr Me 4-NH 2 F-641 NH-n-Bu NH-n-Bu Me 4-NH 2 F-691 NHNH 2 NH-n-Bu Me 4-NH 2 F-642 NH-n-Bu NH-allyl Me 4-NH 2 F-692 NHNH 2 NH-allyl Me 4-NH 2 F-643 NH-n-Bu NH-propargyl Me 4-NH 2 F-693 NHNH 2 NH-propargyl Me 4-NH 2 F-644 NH-n-Bu NHCH 2 CF 3 Me 4-NH 2 F-694 NHNH 2 NHCH 2 CF 3 Me 4-NH 2 F-645 NH-n-Bu NHCH 2 CH 2 F Me 4-NH 2 F-695 NHNH 2 NHCH 2 CH 2 F Me 4-NH 2 F-646 NH-allyl NH-allyl Me 4-NH 2 F-696 NHNHMe NHMe Me 4-NH 2 F-647 NH-allyl NH-Propargyl Me 4-NH 2 F-697 NHNHMe NHEt Me 4-NH 2 F-648 NH-allyl NHCH 2 CF 3 Me 4-NH 2 F-698 NHNHMe NHPr Me 4-NH 2 F-649 NH-allyl NHCH 2 CH 2 F Me 4-NH 2 F-699 NHNHMe NH-i-Pr Me 4-NH 2 F-650 NH-propargyl NH-propargyl Me 4-NH 2 F-700 NHNHMe NHCH 2 CF 3 Me 4-NH 2 Compound No. R 15 R 16 R 17 R 18 Compound No. R 15 R 16 R 17 R 18 F-701 NH 2 NH 2 H 4-NH 2 F-751 NH-propargyl NHCH 2 CF 3 H 4-NH 2 F-702 NH 2 NHMe H 4-NH 2 F-752 NH-propargyl NHCH 2 CH 2 F H 4-NH 2 F-703 NH 2 NHEt H 4-NH 2 F-753 NHCH 2 CF 3 NHCH 2 CF 3 H 4-NH 2 F-704 NH 2 NHPr H 4-NH 2 F-754 NHCH 2 CF 3 NHCH 2 CH 2 F H 4-NH 2 F-705 NH 2 NH-i-Pr H 4-NH 2 F-755 NHCH 2 CH 2 F NHCH 2 CH 2 F H 4-NH 2 F-706 NH 2 NH-n-Bu H 4-NH 2 F-756 NHOMe NH 2 H 4-NH 2 F-707 NH 2 NH-allyl H 4-NH 2 F-757 NHOMe NHMe H 4-NH 2 F-708 NH 2 NH-propargyl H 4-NH 2 F-758 NHOMe NHEt H 4-NH 2 F-709 NH 2 NHCH 2 CF 3 H 4-NH 2 F-759 NHOMe NHPr H 4-NH 2 F-710 NH 2 NHCH 2 CH 2 F H 4-NH 2 F-760 NHOMe NH-i-Pr H 4-NH 2 F-711 NHMe NHMe H 4-NH 2 F-761 NHOMe NH-n-Bu H 4-NH 2 F-712 NHMe NHEt H 4-NH 2 F-762 NHOMe NH-allyl H 4-NH 2 F-713 NHMe NHPr H 4-NH 2 F-763 NHOMe NH-propargyl H 4-NH 2 F-714 NHMe NH-i-Pr H 4-NH 2 F-764 NHOMe NHCH 2 CF 3 H 4-NH 2 F-715 NHMe NH-n-Bu H 4-NH 2 F-765 NHOMe NHCH 2 CH 2 F H 4-NH 2 F-716 NHMe NH-allyl H 4-NH 2 F-766 NHOEt NH 2 H 4-NH 2 F-717 NHMe NH-propargyl H 4-NH 2 F-767 NHOEt NHMe H 4-NH 2 F-718 NHMe NHCH 2 CF 3 H 4-NH 2 F-768 NHOEt NHEt H 4-NH 2 F-719 NHMe NHCH 2 CH 2 F H 4-NH 2 F-769 NHOEt NHPr H 4-NH 2 F-720 NHEt NHEt H 4-NH 2 F-770 NHOEt NH-i-Pr H 4-NH 2 F-721 NHEt NHPr H 4-NH 2 F-771 NHOEt NH-n-Bu H 4-NH 2 F-722 NHEt NH-i-Pr H 4-NH 2 F-772 NHOEt NH-allyl H 4-NH 2 F-723 NHEt NH-n-Bu H 4-NH 2 F-773 NHOEt NH-prepargy H 4-NH 2 F-724 NHEt NH-allyl H 4-NH 2 F-774 NHOEt NHCH 2 CF 3 H 4-NH 2 F-725 NHEt NH-propargyl H 4-NH 2 F-775 NHOEt NHCH 2 CH 2 F H 4-NH 2 F-726 NHEt NHCH 2 CF 3 H 4-NH 2 F-776 NHNMe 2 NH 2 H 4-NH 2 F-727 NHEt NHCH 2 CH 2 F H 4-NH 2 F-777 NHNMe 2 NHMe H 4-NH 2 F-728 NHPr NHPr H 4-NH 2 F-778 NHNMe 2 NHEt H 4-NH 2 F-729 NHPr NH-i-Pr H 4-NH 2 F-779 NHNMe 2 NHPr H 4-NH 2 F-730 NHPr NH-n-Bu H 4-NH 2 F-780 NHNMe 2 NH-i-Pr H 4-NH 2 F-731 NHPr NH-allyl H 4-NH 2 F-781 NHNMe 2 NH-n-Bu H 4-NH 2 F-732 NHPr NH-propargyl H 4-NH 2 F-782 NHNMe 2 NH-allyl H 4-NH 2 F-733 NHPr NHCH 2 CF 3 H 4-NH 2 F-783 NHNMe 2 NH-proparsyl H 4-NH 2 F-734 NHPr NHCH 2 CH 2 F H 4-NH 2 F-784 NHNMe 2 NHCH 2 CF 3 H 4-NH 2 F-735 NH-i-Pr NH-i-Pr H 4-NH 2 F-785 NHNMe 2 NHCH 2 CH 2 F H 4-NH 2 F-736 NH-i-Pr NH-n-Bu H 4-NH 2 F-786 NHNH 2 NH 2 H 4-NH 2 F-737 NH-i-Pr NH-allyl H 4-NH 2 F-787 NHNH 2 NHMe H 4-NH 2 F-738 NH-i-Pr NH-propargyl H 4-NH 2 F-788 NHNH 2 NHEt H 4-NH 2 F-739 NH-i-Pr NHCH 2 CF 2 H 4-NH 2 F-789 NHNH 2 NHPr H 4-NH 2 F-740 NH-i-Pr NHCH 2 CH 2 F H 4-NH 2 F-790 NHNH 2 NH-i-Pr H 4-NH 2 F-741 NH-n-Bu NH-n-Bu H 4-NH 2 F-791 NHNH 2 NH-n-Bu H 4-NH 2 F-742 NH-n-Bu NH-allyl H 4-NH 2 F-792 NHNH 2 NH-allyl H 4-NH 2 F-743 NH-n-Bu NH-propargyl H 4-NH 2 F-793 NHNH 2 NH-propargyl H 4-NH 2 F-744 NH-n-Bu NHCH 2 CFs H 4-NH 2 F-794 NHNH 2 NHCH 2 CF 3 H 4-NH 2 F-745 NH-n-Bu NHCH 2 CH 2 F H 4-NH 2 F-795 NHNH 2 NHCH 2 CH 2 F .H 4-NH 2 F-746 NH-allyl NH-allyl H 4-NH 2 F-796 NHNHMe NHMe H 4-NH 2 F-747 NH-allyl NH-propargyl H 4-NH 2 F-797 NHNHMe NHEt H 4-NH 2 F-748 NH-allyl NHCH 2 CF 3 H 4-NH 2 F-798 NHNHMe NHPr H 4-NH 2 F-749 NH-allyl NHCH 2 CH 2 F H 4-NH 2 F-799 NHNHMe NH-i-Pr H 4-NH 2 F-750 NH-propargyl NH-propargyl H 4-NH 2 F-800 NHNHMe NHCH 2 CF 3 H 4-NH 2 Test Example 1 Inhibitory effect against cellular signaling derived from Ras oncogene products 1) Establishment of cell lines used in assay Based on the reporter plasmid (pGV-P (Toyo Ink, Japan)), in which luciferase gene was ligated to SV40-derived minimal promoter, we constructed a plasmid designated pRRE3-luc by inserting 3 copies of chemically synthesized oligonucleotides ( Sequence: CAGGATATGACTCT, derived from mouse NVL-3 (M.A.Reddy et al.(1992)Mol. Endocrinol., 6,1051)) into upstream of the promoter. v-ki-ras-transformed NIH3T3 cells (DT cells, provided by Dr. Makoto Noda (Kyoto Univ., School of medicine)) were transfected with this plasmid by liposome-mediated transfection and transfected cell lines stably incorporated and maintained each plasmid were obtained. We named pGV-P and pRRE3-transfected cell line as DT-C and DT-R, respectively and used in the assay described below. 2) Preparation of samples i) All the cell lines were cultured in Dulbecco's Modified Essential Medium (DMEM : 10% Fetal Calf Serum(FCS : Hyclone, USA)) including 60 mg/ml kanamycin (Meiji Seika, Japan) in humidified incubator under condition of 5% CO 2 at 37°C. ii) DT-C and DT-R cells were seeded at 2500 cells/well into flat-bottom 96 well multiplate (Sumitomo bakelite) and incubated for 24 hours. iii) Test compounds were prepared as 1 mg/ml DMSO solution. iv) The solution of test compounds were added to the culture. Tested compounds are used at the concentration from 10 mg/ml to 0.51 ng/ml with 3-fold dilution. v) After 24 hours, the culture supernatant was completely aspirated and 20 µl of cell-lysing solution (PGC-50 (Toyo Ink, Japan)) was added before cells were dried up. In order to lyse the cells completely, multiwell plates were left at room temperature for 10 to 30 min. The plates were wrapped up and stored at -20 °C till the day of measurement. 3) Measurement of samples i) Melt the samples by putting 96 well multiplate at 37 °C and add 90 µl/well mM Tris (pH 7.5). ii) Transfer 50 µl of the sample (110 µl) to the 96 well microplate (Microlite 1 (Dynatech)) for measurement. iii) Measure the samples by the luminometer, LUMINOUS CT9000D (Dia-Yatron, Japan). We used Pickagene luminescence kit PGL2000 or LT2.0 (Toyo Ink, Japan) as enzyme substrates for luminescence measurement (50 µl/well). 4) Judgment of the results i) The luciferase activity of DT-C cells and DT-R cells were plotted in the graph where the relative activity and the compound concentration were expressed as Y-axis and X-axis, respectively. We judged by the degree of dissociation between the activities of DT-C cells and DT-R cells as an index. ii) Concretely, efficacy of the compound was expressed by two values described below. a) Among the points of concentration tested, the minimal concentration (Minimal Active Concentration : MAC), at which the activities of DT-C cells and DT-R cells dissociated, was shown as an index of efficacy of the compound. b) Among the points of concentration tested, the concentration which is the nearest to 50% inhibition concentration at DT-C cells (IC50-C), was shown as an index of nonspecific transcription-inhibitory effect or of cytotoxicity. In case of positive compounds, 50% inhibition concentration in DT-C cells which was higher than the active concentration was expressed as IC 50 -C. The results of the assay were shown in table 33. Compound No. MAC (µg/ml) IC50 (µg/ml) Compound No. MAC (µg/ml) IC50 (µg/ml) A-1 1.11 >10 A-16 <0.000508 >10 A-2 1.11 >10 A-17 0.0412 >10 A-3 0.37 >10 A-18 0.00457 >10 A-4 0.37 >10 A-19 0.37 >10 A-5 0.123 10 A-21 0.37 10 A-6 0.0412 10 A-22 1.11 >10 A-7 0.12.3 3.33 A-23 3.33 >10 A-8 0.123 >10 A-32 0.123 >10 A-10 1.11 >10 A-33 0.0412 >10 A-11 0.0412 >10 A-34 0.0137 >10 A-12 0.0137 >10 A-35 0.0412 >10 A-13 0.0137 10 C-1 0.0412 10 A-14 0.0412 >10 C-2 0.0137 >10 A-15 0.00152 >10 Test Example 2 In vitro cell growth inhibition test Cells and MTT assay Human squamous lung cancer RERF-RC-AI, human squamous lung cancer Ma44, human lung adenocarcinoma A549, human colon cancer HT29 and human pancreas cancer PANC-1 were used. All cell lines were cultured with Eagle's Modified Essential Medium (EMEM, supplemented with 10% fetal calf serum (FCS: Hyclone, USA) and 60 µg/ml Kanamycin (Meiji-seika, Japan) at 37 °C in a humidified incubator (5% CO 2 ). The cells were plated in 96-well microcultureplate. Twenty-four hours later, compound were added at the concentration from 10 µg/ml to 0.1 ng/ml with 2-fold dilution. MTT assay was performed 4 days later and IC 50 values were determined. The results were shown in Table 34 in terms of concentration at ng/ml. Compound No. A549 HT-29 Ma44 PANC-1 RERF-LC-AI H460 A-1 0.9 45 120 46 A-2 34 140 370 160 A-3 63 52 56 51 46 A-4 38 23 51 26 30 A-5 70 48.4 44.6 66.5 33 89 A-6 25.6 24.4 18.2 14.8 15 25.6 A-7 2.1 3.6 1.6 0.6 1.3 3.8 A-8 9.3 41.4 34.1 37.1 27.8 6.8 A-10 80 A-11 14 6.7 77 6.4 A-12 8 6.3 9.5 9.1 5.7 11.5 A-13 15 8.9 30 7.7 A-14 12 11 32 9.8 12 A-15 11.1 10.3 12.7 12.4 6.5 15.3 A-16 14.6 8.1 13.6 6.5 7.3 10.7 A-17 17.4 15 24.1 10.7 13.2 15 A-18 51.4 0.4 0.4 0.4 0.4 27.5 A-19 83 A-21 22 A-22 42 A-32 64 31 42 34 31 A-33 23 6.6 9.1 8.6 9.3 A-34 21 4.6 9.1 7.5 13 A-35 11 3.3 6.9 5.4 6.7 C-1 16 6.6 11 6.4 C-2 4.4 2 3.4 2 Formulation example Formulation example 1 Granules are prepared using the following ingredients. Ingredients The compound represented by the formula (I) 10 mg Lactose 700 mg Corn starch 274 mg HPC-L 16 mg 1000 mg The compound represented by the formula (I) and lactose were made pass through a 60 mesh sieve. Corn starch was made pass through a 120 mesh sieve. They were mixed by a twin shell blender. An aqueous solution of HPC-L (low mucosity hydroxypropylcellulose) was added to the mixture and the resulting mixture was kneaded, granulated (by the extrusion with pore size 0.5 to 1 mm mesh), and dried. The dried granules thus obtained were sieved by a swing sieve (12/60 mesh) to yield the granules. Formulation 2 Powders for filling capsules are prepared using the following ingredients. Ingredients The compound represented by the formula (I) 10 mg Lactose 79 mg Corn starch 10 mg Magnesium stearate 1 mg 100 mg The compound represented by the formula (I) and lactose were made pass through a 60 mesh sieve. Corn starch was made pass through a 120 mesh sieve. These ingredients and magnesium stearate were mixed by a twin shell blender. 100 mg of the 10-fold trituration was filled into a No. 5 hard gelatin capsule. Formulation 3 Granules for filling capsules are prepared using the following ingredients. Ingredients The compound represented by the formula (I) 15 mg Lactose 90 mg Corn starch 42 mg HPC-L 3 mg 150 mg The compound represented by the formula (I) and lactose were made pass through a 60 mesh sieve. Corn starch was made pass through a 120 mesh sieve. After mixing them, an aqueous solution of HPC-L was added to the mixture and the resulting mixture was kneaded, granulated, and dried. After the dried granules were lubricated, 150 mg of that were filled into a No. 4 hard gelatin capsule. Formulation 4 Tablets are prepared using the following ingredients. Ingredients The compound represented by the formula (I) 10 mg Lactose 90 mg Microcrystal cellulose 30 mg CMC-Na 15 mg Magnesium stearate 5 mg 150 mg The compound represented by the formula (I), lactose, microcrystal cellulose, and CMC-Na (carboxymethylcellulose sodium salt) were made pass through a 60 mesh sieve and then mixed. The resulting mixture was mixed with magnesium stearate to obtain the mixed powder for the tablet formulation. The mixed powder was compressed to yield tablets of 150 mg. Industrial Applicability The pyrimidine derivatives of the present invention have an inhibitory activity against a signal derived from Ras oncogene products, whereby they are effective for solid cancer having high frequency ras activation such as pancreatic cancer, colon cancer, and lung cancer.

Claims: A compound represented by the formula (I): wherein R 1 , R 2 , R 3 , and R 4 are each independently hydrogen atom, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted aralkyl, an optionally substituted non-aromatic heterocyclic group, acyl, optionally substituted amino, alkyloxy, hydroxy, cyano, or nitro; or R 1 and R 2 , R 3 and R 4 , and R 2 and R 3 each taken together with the adjacent nitrogen atom form the same or different 3- to 7- membered ring optionally containing O, N, or S, provided that R 1 and R 2 and R 3 and R 4 do not form a ring when R 2 and R 3 taken together form a ring; R 5 and R 6 are each independently hydrogen atom, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted alkyloxy, alkylthio, optionally substituted alkyloxycarbonyl, optionally substituted aryl, optionally substituted heteroaryl, halogen, hydroxy, mercapto, optionally substituted amino, carboxy, cyano, or nitro; R B and R C are each independently hydrogen atom, alkyl, or alkyloxy; provided that in the case of both of R B and R C are hydrogen atom, R 1 is hydrogen atom or alkyl, R 2 is substituted amino, alkyloxy, hydroxy, cyano, or nitro; and R 3 and R 4 are each independently hydrogen atom, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted aryl; optionally substituted heteroaryl, optionally substituted aralkyl, optionally substituted non-aromatic heterocyclic group, acyl, optionally substituted amino, alkyloxy, hydroxy, cyano, or nitro; or R 3 and R 4 each taken together with the adjacent nitrogen atom form the same or different 3- to 7- membered ring optionally containing O, S, or N; X is -N(R 7 )-, -NH-NH-, -O-, or -S- wherein R 7 is hydrogen atom or optionally substituted alkyl; Y is optionally substituted 5- membered non-aromatic heterocycle-diyl or optionally substituted 5- membered heteroaryl-diyl; Z is optionally substituted aryl or optionally substituted heteroaryl; its optical active compound, its prodrug thereof, or their pharmaceutically acceptable salt, or their solvate. A compound of claim 1, represented by the formula (II): wherein R 8 , R 9 , R 10 , and R 11 are each independently hydrogen atom, optionally substituted alkyl, alkenyl, alkynyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted aralkyl, a non-aromatic heterocyclic group, acyl, substituted amino, alkyloxy, hydroxy, cyano, or nitro; R B and R C are each independently hydrogen atom, alkyl, or alkyloxy; provided that in the case of both of R B and R C are hydrogen atom, R 8 is hydrogen atom or alkyl, R 9 is substituted amino, alkyloxy, hydroxy, cyano, or nitro; and R 10 and R 11 are each independently hydrogen atom, optionally substituted alkyl, alkenyl, alkynyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted aralkyl, non-aromatic heterocyclic group, acyl, optionally substituted amino, alkyloxy, hydroxy, cyano, or nitro; W is -O-, -S-, or -N(R A )- wherein R A is hydrogen atom or optionally substituted alkyl; R 5 , R 6 , X, and Z are as defined in claim 1; its optical active compound, its prodrug thereof, or their pharmaceutically acceptable salt, or their solvate. A compound of claim 1, represented by the formula (III): wherein R 5 , R 6 , and Z are as defined in claim 1, R 8 , R 9 , R 10 , R 11 , R B and R C are as defined claim 2, their optical active compounds, the prodrugs thereof, or their pharmaceutically acceptable salts, or their solvates. A compound of claim 1, represented by the formula (IY): wherein R 8 , R 9 , R 10 and R 11 are as defined in claim 2; R 12 is hydrogen atom or alkyl; R D and R E are each independently hydrogen atom or alkyl; provided that in the case of both of R D and R E are hydrogen atom, R 8 is hydrogen atom or alkyl, R 9 is substituted amino, alkyloxy, hydroxy, cyano, or nitro; and R 10 and R 11 are each independently hydrogen atom, optionally substituted alkyl, alkenyl, alkynyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted aralkyl, non-aromatic heterocyclic group, acyl, optionally substituted amino, alkyloxy, hydroxy, cyano, or nitro; V is optionally substituted aryl; its optical active compound, its prodrug thereof, or their pharmaceutically acceptable salt, or their solvate. A compound of claim 1, represented by the formula (V): wherein R 5 and R 6 are each independently hydrogen atom, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted alkyloxy, alkylthio, optionally substituted alkyloxycarbonyl, optionally substituted aryl, optionally substituted heteroaryl, halogen atoms, hydroxy, mercapto, optionally substituted amino, carboxy, cyano, or nitro; R F and R G are each independently hydrogen atom, alkyl, or alkyloxy; X is -N(R 7 )-, -NH-NH-, -O-, or -S- wherein R 7 is hydrogen atom or optionally substituted alkyl; Y is optionally substituted 5- membered non-aromatic heterocycle-diyl or optionally substituted 5- membered heteroaryl-diyl; Z is optionally substituted aryl or optionally substituted heteroaryl; Q 1 is -NR 1 R 2 , -OR 1 , or -SR 1 , T 1 is -OR 3 or -SR 3 wherein R 1 , R 2 and R 3 are each independently hydrogen atom, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted aryl, optionally-substituted heteroaryl, optionally substituted aralkyl, optionally substituted non-aromatic heterocyclic group, acyl, optionally substituted amino, alkyloxy, hydroxy, cyano, or nitro; or R 1 and R 3 , and R 2 and R 3 each taken together with the adjacent heteroatom form 5- to 7-membered ring; its optical active compound, its prodrug thereof, or their pharmaceutically acceptable salt, or their solvate. A compound of calim 5, represented by the formula (VI): wherein Q 2 is -NR 8 R 9 , -OR 8 , or -SR 8 , T 2 is -OR 10 or -SR 10 wherein R 8 , R 9 and R 10 are each independently hydrogen atom, optionally substituted alkyl, alkenyl, alkynyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted aralkyl, optionally substituted non-aromatic heterocyclic group, acyl, optionally substituted amino, alkyloxy, hydroxy, cyano, or nitro; W is -O-, -S-, or -N(R A )- wherein R A is hydrogen atom or optionally substituted alkyl; R 5 , R 6 , R F , R G , X, and Z are as defined in claim 5; its regioisomer, its optical active compound, its prodrug thereof, or their pharmaceutically acceptable salt, or their solvate. A compound of claim 5, represented by the formula (VII): wherein R 5 , R 6 , R F , R G , and Z are as defined in claim 5; Q 2 and T 2 are as defined in claim 6; its regioisomer, its optical active compound, its prodrug thereof, or their pharmaceutically acceptable salt, or their solvate. A compound of claim 5, represented by the formula (VIII): wherein R 12 is hydrogen or alkyl; R H and R J are each independently hydrogen atom or alkyl; the other symbols are as defined in claim 6; its regioisomer, its optical active compound, its prodrug thereof, or their pharmaceutically acceptable salt, or their solvate. A compound, its regioisomer, its optical active compound, its prodrug thereof, or their pharmaceutically acceptable salt, or their solvate of claim 1 or 5, wherein R 1 , R 2 , R 3 , and R 4 are each independently hydrogen atom, optionally substituted alkyl, alkenyl, alkynyl, or acyl. A compound, its regioisomer, its optical active compound, its prodrug thereof, or their pharmaceutically acceptable salt, or their solvate of any one of claims 2 to 4 or claims 6 to 8, wherein R 8 , R 9 , R 10 , and R 11 are each independently hydrogen atom, optionally substituted alkyl, alkenyl, alkynyl, or acyl. A pharmaceutical composition which contains as active ingredient a compound as described in any one of claims 1 to 10. Use of a compound as described in any one of claims 1 to 10 for the preparation of a pharmaceutical composition for use as an antitumor agent. Use of a compound as described in any one of claims 1 to 10 for the preparation of a pharmaceutical composition for use as a cytostatic agent. Use of a compound as described in any one of claims 1 to 10 for the preparation of a pharmaceutical composition for use as an inhibitor against a signal derived from Ras oncogene products. Use of a compound of any one of claims 1 to 10 for the preparation of a pharmaceutical composition for treating cancer. Use of a compound as described in any one of claims 1 to 10 for the preparation of a pharmaceutical composition for treating a mammal, including a human, to alleviate a pathological effect of cancer.

Inventors: SUZUKI SHINJI, TAKENAKA HIDEYUKI, TANAKA HIDEKAZU, UEDA KAZUO, SUZUKI, SHINJI, TAKENAKA, HIDEYUKI, TANAKA, HIDEKAZU, UEDA, KAZUO, SUZUKI, Shinji c/o Shionogi &amp; Co., Ltd., TAKENAKA, Hideyuki c/o Shionogi &amp; Co., Ltd., TANAKA, Hidekazu c/o Shionogi &amp; Co., Ltd., UEDA, Kazuo c/o Shionogi &amp; Co., Ltd.
Applicants: SHIONOGI & CO, SHIONOGI & CO., LTD.
Application year: 2001
Main classification: C07D413
IPC codes: A61P35, C07D413