3,4-Diarylpiperidines as potent renin inhibitors

详细信息    查看全文

• 作者：Patrick Lacombe ; ^{lacombepatrick@hotmail.com} ; Mé ; lissa Arbour ; René ; e Aspiotis ; Elizabeth Cauchon ; Austin Chen ; Daniel Dubé ; Jean-Pierre Falgueyret ; Pierre-André ; Fournier ; Michel Gallant ; Erich Grimm ; Yongxin Han ; Hé ; lè ; ne Juteau ; Suzanna Liu ; Christophe Mellon ; Yeeman Ramtohul ; Daniel Simard ; René ; St-Jacques ; Gavin Chit Tsui
• 关键词：Renin ; Inhibitor ; Anti-hypertensive
• 刊名：Bioorganic and Medicinal Chemistry Letters
• 出版年：2012
• 出版时间：1 March, 2012
• 年：2012
• 卷：22
• 期：5
• 页码：1953-1957
• 全文大小：566 K

文摘

The discovery and SAR of a series of potent renin inhibitors possessing a novel 3,4-diarylpiperidine scaffold are described herein. The resulting compound 38 exhibit low nanomolar plasma renin IC₅₀, had a clean CYP 3A4 profile and displayed micromolar affinity for the hERG channel. Furthermore, it was found to be efficacious in the double transgenic rat hypertension model and show good to moderate oral bioavailability in two animal species.