Darren Dressen,
Albert W Garofalo,
Jon Hawkinson, Dennis Hom,
Jacek Jagodzinski,
Jennifer L Marugg,
Martin L Neitzel,
Michael A Pleiss,
Balazs Szoke,
Jay S Tung,
David W G Wone,
Jing Wu,
Heather Zhang
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ABSTRACT: The B1 receptor is an attractive target for the treatment of pain and inflammation. A series of 3-carboxamido-5-phenacylamino pyrazole B1 receptor antagonists are described that exhibit good potency against B1 and high selectivity over B2. Initially, N-unsubstituted pyrazoles were studied, but these compounds suffered from extensive glucuronidation in primates. This difficulty could be surmounted by the use of N-substituted pyrazoles. Optimization efforts culminated in compound 41, which has high receptor potency and metabolic stability.
Journal of Medicinal Chemistry 11/2007; 50(21):5161-7. · 5.25 Impact Factor
