3,4-Diarylpiperidines as potent renin inhibitors

Autor:	Mélissa Arbour, Gavin Chit Tsui, Jean-Pierre Falgueyret, Pierre-André Fournier, Yongxin Han, Michel Gallant, Patrick Lacombe, Daniel Dube, Daniel Simard, Elizabeth Cauchon, Austin Chen, Renee Aspiotis, Suzanna Liu, René St-Jacques, Christophe Mellon, Erich L. Grimm, Yeeman K. Ramtohul, Helene Juteau
Rok vydání:	2011
Předmět:	Transgene Clinical Biochemistry hERG Pharmaceutical Science Biological Availability Pharmacology Biochemistry Plasma renin activity Rats Sprague-Dawley Structure-Activity Relationship Dogs Piperidines Drug Discovery Renin–angiotensin system Renin Structure–activity relationship Animals Cytochrome P-450 CYP3A Humans Animal species Molecular Biology Antihypertensive Agents Cytochrome P-450 CYP3A Inhibitors biology Chemistry Organic Chemistry Ether-A-Go-Go Potassium Channels Bioavailability Rats Hypertension biology.protein Molecular Medicine Rats Transgenic
Zdroj:	Bioorganicmedicinal chemistry letters. 22(5)
ISSN:	1464-3405
Popis:	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 IC(50), 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.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::72bbcef3547c253b1c7b45e16084feb3 https://pubmed.ncbi.nlm.nih.gov/22325946 Zobrazit plný text záznamu Full Text from ScienceDirect