From Bradykinin B2 Receptor Antagonists to Orally Active and Selective Bradykinin B1 Receptor Antagonists

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• 作者：Martine Barth ; Michel Bondoux ; Jean-Michel Luccarini ; Vincent Peyrou ; Pierre Dodey ; Didier Pruneau ; Christine Massardier ; Jean-Luc Paquet
• 刊名：Journal of Medicinal Chemistry
• 出版年：2012
• 出版时间：March 22, 2012
• 年：2012
• 卷：55
• 期：6
• 页码：2574-2584
• 全文大小：434K
• 年卷期：v.55,no.6(March 22, 2012)
• ISSN：1520-4804

文摘

The bradykinin (BK) B1 receptor is an attractive target for the treatment of chronic pain and inflammation. Starting from a dual B1 and B2 antagonist, novel antagonists were designed that display low-nanomolar affinity for human B1 receptor and selectivity over B2. Initially, potent imidazoline derivatives were studied, but these compounds suffered from low bioavailability. This issue could be overcome by the use of less basic amino derivatives leading to orally active compounds.