| 摘要 |
PURPOSE: Provided are a compound with aryl-amidines, particularly amidinoaryl-cyclopropanes, amidinoarylmethyl-pyrroles, amidinoaryl-benzenes, amidinoaryl-pyridines, or amidinoaryl-alanines, represented by formula (1), a pharmaceutically acceptable salt, a prodrug, a hydrate, a solvate or an isomer thereof, which are inhibitors of coagulation enzyme, factor Xa (FXa). Also, provided are a pharmaceutical composition containing the compound, and a method of using the same as an anticoagulant agent for the treatment and the prevention of thrombosis disorders. CONSTITUTION: The novel compound of the formula(1) has a good FXa inhibition activity and consequently an excellent selectivity against trypsin and thrombin. In the formula(1), Ar is selected from the groups consisting of benzene, pyridine, thiophene, naphthalene and isoquinoline; G is selected from the groups consisting of R, F, Cl, Br, I, CN, OR, OCOR, CO2R and CONR2, where R represents H or a linear, branched, cyclic or branched cyclic alkyl group having 1 to 10 of carbon atoms; A is selected from the groups consisting of Al, A2, A3 and A4; D represents-NH2, or-CH2NH2; L is a simple linker and represents -(CH2)m-(m = 0, 1); P is selected from the groups consisting of phenyl, pyridine, pyrrole, furan, thiophene, oxazole, isoxazole, imidazole, 1, 2-diazole, thiazole, isothiazole, pyridazine(1, 2-diazine), pyrimidine, pyrazine(1, 4-diazine), naphthalene, quinoline, isoquinoline, benzofuran, benzothiophene, and indole; X is selected from the groups consisting of R, F, Cl, Br, I, CN, OR, COA COR, CONR2, NR2, NR((C=O) R), CF3, OCF3, SO2NR2, SONR2, SO2R, SOR, N ((C=O) R)2, imidazole, 1, 2-diazole, thiazole, isothiazole, pyridazine(= 1, 2-diazine), pyrimidine, pyrazine(= 1, 4-diazine), 1, 2, 3-triazole, 1, 2, 4-triazole, tetrazole, 1, 3, 5-triazine, (1, 2)-imidazoline-2-yl, N-methyl- (1, 2)-imidazoline-2-yl, and NHC (=NR) R; n represents a number of 0, 1 or 2; Q represents hydrogen or is selected from the groups consisting of phenyl, pyridine,pyrrole, furan, thiophene, oxazole, isoxazole, imidazole, 1, 2-diazole, thiazole, isothiazole, pyridazine(= 1, 2-diazine), pyrimidine, and pyrazine(= 1, 4-diazine), provided that when Q represents hydrogen, the substituents Y and Z are meant to be directly connected to P; and Y and Z are independently selected from the group consisting of R, F, Cl, Br, I, CN, OR, COA COR, CONR2, NR2, NR((C=O) R), N((C=O) R)2, CF3, OCF3, SO2NR2, SONR2, SOA SOR, imidazole, 1, 2-diazole, thiazole, isothiazole, pyridazine (=1, 2-diazine), pyrimidine, pyrazine (= 1, 4-diazine), 1, 2, 3-triazole, 1, 2, 4-triazole, tetrazole and 1, 3, 5-triazine.
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