Design and discovery of new (3S,5R)-5-[4-(2-chlorophenyl)-2,2-dimethyl-5-oxopiperazin-1-yl]piperidine-3-carboxamides as potent renin inhibitors

Utilizing X-ray crystal structure analysis, (3S,5R)-5-[4-(2-chlorophenyl)-2,2-dimethyl-5-oxopiperazin-1-yl]piperidine-3-carboxamides were designed and identified as renin inhibitors. The most potent compound 15 demonstrated favorable pharmacokinetic and pharmacodynamic profiles in rat.

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Veröffentlicht in:	Bioorganic & medicinal chemistry letters 2012-12, Vol.22 (24), p.7677-7682
Hauptverfasser:	Mori, Yutaka, Ogawa, Yasuyuki, Mochizuki, Akiyoshi, Nakamura, Yuji, Sugita, Chie, Miyazaki, Shojiro, Tamaki, Kazuhiko, Matsui, Yumi, Takahashi, Mizuki, Nagayama, Takahiro, Nagai, Yoko, Inoue, Shin-ichi, Nishi, Takahide
Format:	Artikel
Sprache:	eng
Schlagworte:	Angiotensin-Converting Enzyme Inhibitors - chemical synthesis Angiotensin-Converting Enzyme Inhibitors - chemistry Angiotensin-Converting Enzyme Inhibitors - pharmacology Animals Biological and medical sciences chemistry Crystallography, X-Ray Dose-Response Relationship, Drug Drug Discovery Haplorhini Humans Ketopiperazine Medical sciences Models, Molecular Molecular Conformation pharmacokinetics Pharmacology. Drug treatments Piperazines - chemical synthesis Piperazines - chemistry Piperazines - pharmacology Piperidine Piperidines - chemical synthesis Piperidines - chemistry Piperidines - pharmacology rats Renin Renin - antagonists & inhibitors Renin - blood Renin - metabolism Structure-Activity Relationship X-ray crystal structure analysis X-ray diffraction
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Beschreibung
Zusammenfassung:	Utilizing X-ray crystal structure analysis, (3S,5R)-5-[4-(2-chlorophenyl)-2,2-dimethyl-5-oxopiperazin-1-yl]piperidine-3-carboxamides were designed and identified as renin inhibitors. The most potent compound 15 demonstrated favorable pharmacokinetic and pharmacodynamic profiles in rat.
ISSN:	0960-894X 1464-3405
DOI:	10.1016/j.bmcl.2012.09.103