Preparation of substituted imidazoles as TAFIa inhibitors

Abstract

Imidazoles R1C3H2N2-CR2R3CH(CO2H)-X(R4)CR5R6(CH2)nCR7R8NR9R10 [C3H2N2 represents the imidazole ring; X = N or CH; n = 0-3; R1 = H, (un)substituted alkyl, alkenyl or alkynyl, heterocyclyl, (hetero)aryl; R2, R3 = H, (un)substituted alkyl or R2R3 = alkylene; R4 = H, (un)substituted alkyl or R4R10 = (un)substituted alkylene; R5, R6 = H, aryl, (un)substituted alkyl or R5R6, R5R10 or R6R10 = alkylene; R7, R8 = H, (un)substituted alkyl or R7R8 = alkylene; R9, R10 = H, an amidino group, (un)substituted alkyl or R9R10 = alkylene] were prepd. as inhibitors of active thrombin activatable fibrinolysis inhibitor (TAFIa) for use in the treatment of disease. Thus, (+-)-6-amino-2-[(1-propyl-1H-imidazol-4-yl)methyl]hexanoic acid was prepd. and showed Ki = 310 nM for inhibition of TAFIa. [on SciFinder (R)]