Preparation and Optimization of a Series of 3-Carboxamido-5-phenacylaminopyrazole Bradykinin B1 Receptor Antagonists

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• 作者：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
• 刊名：Journal of Medicinal Chemistry
• 出版年：2007
• 出版时间：October 18, 2007
• 年：2007
• 卷：50
• 期：21
• 页码：5161 - 5167
• 全文大小：134K
• 年卷期：v.50,no.21(October 18, 2007)
• ISSN：1520-4804

文摘

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 andhigh selectivity over B2. Initially, N-unsubstituted pyrazoles were studied, but these compounds sufferedfrom extensive glucuronidation in primates. This difficulty could be surmounted by the use of N-substitutedpyrazoles. Optimization efforts culminated in compound 41, which has high receptor potency and metabolicstability.