Potent bradykinin B1 receptor antagonists: 4-Substituted phenyl cyclohexanes

Selective bradykinin (BK) B1 receptor antagonists have been shown to be antinociceptive in animal models and could be novel therapeutic agents for the treatment of pain and inflammation. Elucidation of the structure–activity relationships of the biphenyl moiety of the lead compound 1 provided a potent new structural class of BK B1 receptor antagonists.

4-Substituted phenyl cyclohexanes were identified as alternative isosteres for the biphenyl moiety of the lead compound 1. The syntheses, SAR optimization, and pharmacokinetic profiles of these compounds are described.Figure optionsDownload as PowerPoint slide