Author/Authors :
Christopher Fotsch، نويسنده , , Gloria Biddlecome، نويسنده , , Kaustav Biswas، نويسنده , , Jian Jeff Chen، نويسنده , , Derin C. D’Amico، نويسنده , , Robert D. Groneberg، نويسنده , , Nianhe Bruce Han، نويسنده , , Feng-Yin Hsieh، نويسنده , , Augustus Kamassah، نويسنده , , Gondi Kumar، نويسنده , , Dianna Lester-Zeiner، نويسنده , , Qingyian Liu، نويسنده , , David A. Mareska، نويسنده , , Babak Bobby Riahi، نويسنده , , Yueh-Ju Judy Wang، نويسنده , , Kevin Yang، نويسنده , , James Zhan، نويسنده , , Joe Zhu، نويسنده , , Eileen Johnson، نويسنده , , Gordon Ng، نويسنده , , et al، نويسنده ,
Abstract :
The bradykinin 1 (B1) 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 B1 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 IC50s < 20 nM in a B1 receptor functional assay. One of these compounds, 13g, shows modest oral bioavailability in rats.
