Bradykinin B1 receptor antagonists: SAR studies of the aryl-piperidines on the cyclopropane carboxamide scaffold

MEDI 300

Jenny Wai, jenny_wai@merck.com1, Scott D. Kuduk, scott_d_kuduk@merck.com1, Michael R Wood1, Ronald K. Chang, ronald_chang@merck.com1, Dong-Mei Feng1, Kathy L. Murphy2, Richard W. Ransom2, Cuyue Tang3, Thomayant Prueksaritanont4, Roger M. Freidinger1, Douglas Pettibone2, and Mark G. Bock1. (1) Department of Medicinal Chemistry, Merck & Co., Inc, WP14-3, Sumneytown Pike, Post Office Box 4, West Point, PA 19486, (2) Neuroscience Drug Discovery, Merck Research Laboratories, Sumneytown Pike, West Point, PA 19486, (3) Drug Metabolism, Merck Research Laboratories, Sumeytown Pike, West Point, PA 19486, (4) Department of Molecular Endocrinology, and Department of Drug Metabolism, Merck Research Laboratories, Sumeytown Pike, West Point, PA 19486
Bradykinin B1 receptor antagonists are targeted as potential therapeutic agents for the treatment of chronic pain and inflammation. A series of cyclopropane carboxamides containing arylpiperidines as a new scaffold were evaluated. Several of these antagonists showed sub-nanomolar binding affinities for the human bradykinin B1 receptor, and exhibited good pharmacokinetic profiles in both dog and rat.

 

Poster Session
7:00 PM-9:00 PM, Wednesday, August 22, 2007 BCEC -- Exhibit Hall - B2, Poster

Division of Medicinal Chemistry

The 234th ACS National Meeting, Boston, MA, August 19-23, 2007