AU2008200842B2 — Tricyclic thrombin receptor antagonists

USPTO Abstract

Heterocyclic-substituted tricyclics of the formula (I) or a pharmaceutically acceptable salt thereof, wherein: 5 the dotted line represents an optional single bond; ----- represents an optional double bond; n is 0-2; Q is cycloalkyl, optionally substituted by R'3 and R14 ; each R" is independently selected from H, (C,-C6 )alkyl, (03 -C5 )cycloalkyl, 10 -(CH 2)neNHC(O)OR'*O, -(CH 2)neNHC(O)R'", -(CH 2),,6NHC(O)NR 4 R5, -(CH 2)neNHSO 2 R0 , -(CH 2)n6 NH S0 2N R4R, and -(CH 2)nsC(O)NR 28 R29 where ne is 0-4, haloalkyl, and halogen; each R14 is independently selected from H, (C,-C)alkyl, -OH, (C-C)alkoxy, R27-aryl(C1-C5)alkyl, heteroaryl, heteroarylalkyl, heterocycyl, is heterocycylalkyl, -(CH 2)n6NHC(O)OR'b, -(CH2)neNHC(O)R'Ib, -(CH 2)neNHC(O)NR 4R5, -(CH 2)meNHSO 2 R, -(CH 2)n6NHSO 2NR4R5 , and -(CH 2)neC(O)NRaR" where n, is 0-4, halogen and haloalkyl; or R's and R14 taken together form a spirocyclic or a heterospirocyclic ring of 3-6 atoms; 20 wherein at least one of R'5 or R" is selected from the group consisting of -(CH 2)neNHC(O)OR"", -(CH 2)neNHC(O) R'O, -(CH 2)neNHC(O)NR 4R', -(CH2)sNHSO 2 R'6 , -(CH 2),nNHSO 2NRR 6, and -(CH 2)neC(O)NR 2 R29 where na is 04; Het is a mono- or bi-cyclic optionally substituted heteroaryl group; and 25 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. 30 Combination therapy with other cardiovascular agents is also claimed. y- R .3 10 (CH 2)n, R x R R Q (I) Het