TRICYCLIC THROMBIN RECEPTOR ANTAGONISTS

摘要

Heterocyclic-substituted tricyclics of the formula (I) or a pharmaceutically acceptable salt thereof, wherein: the dotted line represents an optional single bond; (a) represents an optional double bond; n is 0-2; Q is cycloalkyl, optionally substituted by R<13> and R<14>; each R<13> is independently selected from H, (C1-C6)alkyl, (C3-C8)cycloalkyl, -(CH2)n6NHC(O)OR<16b>, -(CH2)n6NHC(O)R<16b>, -(CH2)n6NHC(O)NR<4>R<5>, -(CH2)n6NHSO2R<16>, -(CH2)n6NHSO2NR<4>R<5>, and -(CH2)n6C(O)NR<28>R<29> where n6 is 0-4, haloalkyl and halogen; each R<14> is independently selected from H, (C1-C6)alkyl, -OH, (C1-C6)alkoxy, R<27>-aryl (C1-C6)alkyl, heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, -(CH2)n6NHC(O)OR<16b>, -(CH2)n6NHC(O)R<16b>, -(CH2)n6NHC(O)NR<4>R<5>, -(CH2)n6NHSO2R<16>, -(CH2)n6NHSO2NR<4>R<5>, and -(CH2)n6C(O)NR<28>R<29> where n6 is 0-4, halogen and haloalkyl; or R<13> and R<14> taken together form a spirocyclic or a heterospirocyclic ring of 3-6 atoms; wherein at least one of R<13> or R<14> is selected from the group consisting of -(CH2)n6NHC(O)OR<16b>, -(CH2)n6NHC(O)R<16b>, -(CH2)n6NHC(O)NR<4>R<5>, -(CH2)n6NHSO2R<16>, -(CH2)n6NHSO2NR<4>R<5>, and -(CH2)n6C(O)NR<28>R<29> where n6 is 0-4; Het is a mono- or bi-cyclic optionally substituted heteroaryl group; and B is a bond, alkylene, or optionally substituted alkenylene or alkynylene, wherein the remaining substituents are as defined in the specification, are disclosed, as well as pharmaceutical compositions containing them and a method of treating diseases associated with thrombosis, atherosclerosis, restenosis, hypertension, angina pectoris, arrhythmia, heart failure, and cancer by administering said compounds. Combination therapy with other cardiovascular agents is also claimed.