TRICYCLIC THROMBIN RECEPTOR ANTAGONISTS

摘要

Heterocyclic-substituted tricyclics of the formula (I) or a pharmaceutically acceptable salt thereof, wherein: the single dotted line represents an optional single bond; ~ represents an optional double bond; n is 0-2; Q is cycloalkyl, optionally substituted by R13 and R14; each R13 is independently selected from H, (C1-C6)alkyl, (C3-C8)cycloalkyl, -(CH2)n6NHC(O)OR16b, -(CH2)n 6NHC(O)R16b, --(CH2)n6NHC(O)NR4R5, -(CH2)n6NHSO2R16, -(CH2)n6NHSO2NR4R5, and --(CH2)n6C(O)NR28R29 where n6 is 0-4, haloalkyl and halogen; each R14 is independently selected from H, (C1-C6)alkyl, -OH, (C1-C6)alkoxy, R27-aryl (C1--C6)alkyl, heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, -(CH2)n6NHC(O)OR16b, -(CH2)n6NHC(O)R16b, -(CH2)n6NHC(O)NR4R5, -(CH2)n6NHSO2R16, -(CH2)n6NHSO2NR4R5, and -(CH2)n6C(O)NR28R29 where n6 is 0-4, halogen and haloalkyl; or R13 and R14 taken together form a spirocyclic or a heterospirocyclic ring of 3-6 atoms; wherein at least one of R13 or R14 is selected from the group consisting of -(CH2)n6NHC(O)OR16b, -(CH2)n6NHC(O)R16b, -(CH2)n6NHC(O)NR4R5, -(CH2)n6NHSO2R16, -(CH2)n6NHSO2NR4R5, and -(CH2)n6C(O)NR28R29 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. (see formula I)