N-acylpyrrolidines or N-acylpiperidines having a guanidinyl- or amidinyl-substituted side chain as thrombin inhibitors.

摘要

Guanidinyl- or amidinyl-substituted heterocyclic thrombin inhibitors are provided which have the structure wherein n is 0, 1 or 2; R<1> is -A-R<2>, -CO-A-R<2> or -SO2-A-R<2>; wherein R<2> is guanidine, amidine or amino, and A is an alkyl, alkenyl or alkynyl chain of 2 to 6 carbons; or R<1> is -(CH2)p-A'-R<2'> or -(CH2)p-CO-A'R<2'> where p is 0, 1 or 2, R<2'> is amidine and A' is an azacycloalkyl or azaheteroalkyl ring of 4 to 8 atoms, optionally substituted by alkyl, CO or halo; R<1> is -(CH2)p-A''-R<2''>, -(CH2)p-CO-A''-R<2''>, or -(CH2)p-SO2-A''-R<2''>, wherein R<2''>is guanidine, amidine or aminomethyl, and A'' is aryl or cycloalkyl; and R<3>, R<4>, R<5> and R<6> are as defined herein.