EP1982984A2 — Tricyclic thrombin receptor antagonists

USPTO Abstract

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, (C 1 -C 6 )alkyl, (C 3 -C 8 )cycloalkyl, -(CH 2 ) n6 NHC(O)OR 16b , -(CH 2 ) n6 NHC(O)R 16b , -(CH 2 ) n6 NHC(O)NR 4 R 5 , -(CH 2 ) n6 NHSO 2 R 16 , -(CH 2 ) n6 NHSO 2 NR 4 R 5 , and -(CH 2 ) n6 C(O)NR 28 R 29 where n 6 is 0-4, haloalkyl and halogen; each R 14 is independently selected from H, (C 1 -C 6 )alkyl, -OH, (C 1 -C 6 )alkoxy, R 27 -aryl (C 1 -C 6 )alkyl, heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylallryl, -(CH 2 ) n6 NHC(O)OR 16b , -(CH 2 ) n6 NHC(O)R 16b , -(CH 2 ) n6 NHC(O)NR 4 R 5 , -(CH 2 ) n6 NHSO 2 R 16 , -(CH 2 ) n6 NHSO 2 NR 4 R 5 , and -(CH 2 ) n6 C(O)NR 28 R 29 where n 6 is 0-4, halogen and haloalkyl; or R 13 and R 14 taken together form a spirocyclic or a hetetospirocyclic ring of 3-6 atoms; wherein at least one of R 13 or R 14 is selected from the group consisting of -(CH 2 ) n6 NHC(O)OR 16b , -(CH 2 ) n6 NHC(O)R 16b , -(CH 2 ) n6 NHC(O)NR 4 R 5 , -(CH 2 ) n6 NHSO 2 R 16 , -(CH 2 ) n6 NHSO 2 NR 4 R 5 , and -(CH 2 ) n6 C(O)NR 28 R 29 where n 6 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.