Heterocyclic thrombin inhibitors.

摘要

Heterocyclic thrombin inhibitors are provided which have the structure including all stereoisomers thereof wherein n is 0, l or 2; p is 0, l or 2; Q is a single bond or C=O; A is aryl or cycloalkyl, or an azacycloalkyl ring or an azaheteroalkyl ring; R<5> is guanidine, amidine or aminomethyl, but when A is azacycloalkyl or azaheteroalkyl, R<5> is amidine; R<1> and R<2> are independently hydrogen, lower alkyl, cycloalkyl, aryl, hydroxy alkoxy, keto, thioketal, thioalkyl, thioaryl, amino or alkylamino; or R<1> and R<2> together with the carbons to which they are attached form a cycloalkyl aryl, or heteroaryl ring; R<4> is hydrogen, hydroxyalkyl, aminoalkyl, amidoalkyl, alkyl, cycloalkyl, aryl, arylalkyl, alkenyl, alkynyl, arylalkoxyalkyl, or an amino acid side chain, either protected or unprotected; and R<3> is hydrogen, or -CO2R<6> (wherein R<6> is lower alkyl, aryl, arylalkyl or cycloheteroalkyl); including pharmaceutically acceptable salts thereof.