title: 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.
abstract: 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.
authors.affiliation: Lead Discovery & Optimization Research Laboratories I, Daiichi Sankyo Co., Ltd, 1-2-58 Hiromachi, Shinagawa-ku, Tokyo 140-8710, Japan.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Mori
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Ogawa
authors.forename: Akiyoshi
authors.initials: A
authors.lastname: Mochizuki
authors.forename: Yuji
authors.initials: Y
authors.lastname: Nakamura
authors.forename: Chie
authors.initials: C
authors.lastname: Sugita
authors.forename: Shojiro
authors.initials: S
authors.lastname: Miyazaki
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Tamaki
authors.forename: Yumi
authors.initials: Y
authors.lastname: Matsui
authors.forename: Mizuki
authors.initials: M
authors.lastname: Takahashi
authors.forename: Takahiro
authors.initials: T
authors.lastname: Nagayama
authors.forename: Yoko
authors.initials: Y
authors.lastname: Nagai
authors.forename: Shin-ichi
authors.initials: S
authors.lastname: Inoue
authors.forename: Takahide
authors.initials: T
authors.lastname: Nishi
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D018360:Crystallography, X-Ray; D004305:Dose-Response Relationship, Drug; D055808:Drug Discovery; D000882:Haplorhini; D006801:Humans; D008958:Models, Molecular; D008968:Molecular Conformation; D010879:Piperazines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D010880:Piperidines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D012083:Renin / Q000097:blood / Q000378:metabolism; D013329:Structure-Activity Relationship; D000092502:Renin Inhibitors
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D010879:Piperazines; D010880:Piperidines; D012083:Renin; D000092502:Renin Inhibitors; C581120:(3S,5R)-5-(4-(2-chlorophenyl)-2,2-dimethyl-5-oxopiperazin-1-yl)piperidine-3-carboxamide