A new class of bradykinin 1 receptor antagonists containing the piperidine acetic acid tetralin core

The bradykinin 1 (Bl) receptor is upregulated during times of inflammation and is important for maintaining inflamed and chronic pain states. Blocking this receptor has been shown to reverse and/or ameliorate pain and inflammation in animal models. In this report, we describe a new class of Bl receptor antagonists that contain the piperidine acetic acid tetralin core. A structure-activity relationship for these analogs is described in this paper. The most potent compounds from this class have IC 50 s < 20 nM in a Bl receptor functional assay. One of these compounds, 13g, shows modest oral bioavailability in rats.