SELECTIVE FXA INHIBITOR HAVING CYCLOPROPYL STRUCTURE

摘要

PURPOSE: A selective FXa inhibitor having a cyclopropyl structure is provided, which shows the improved selectivity to similar enzymes such as trypsin and thrombin. CONSTITUTION: Cyclopropyl derivatives are represented by formula (1), in which D is selected from amino, aminoiminomethyl and aminomethyl; A is phenyl, hydroxyphenyl, pyridine, thiophene, pyrimidine, naphthalene, quinoline, isoquinoline, benzofuran, benzothiophene and indole; R1 and R2 is individually H, F, Cl, Br, I, CN, CHO, CH2OR wherein R is hydrogen or linear, branched or ring lower alkyl having carbon number of 10 or less, CO2R, COR, CONR2, CH2NR2, CH2NR(C=O)R, CH2NR(SO2)R, CH2N(SO2R)2 and R; L is a linker and (CH2)m, wherein m is 0 or 1; P and Q are individually phenyl, pyridine, pyrol, furan, thiophene, oxazole, isooxazole, imidazole, 1,2-diazole, thiazole, isothiazole, pyridazine, pyrimidine, pyrazine, 1,2,3-triazole, 1,2,4-triazole, tetrazole and 1,3,5-triazine; X, Y and Z are individually H, F, Cl, Br, I, CN, CHO, OR, R, NR2, CO2R, COR, CONR2, NR(C=O)R, N((C=O)R)2, SO2NR2, SO2R, CF3, OCF3 and C(=NH)NH; and n is 0, 1, 2.