title: Synthesis, biological evaluation and docking studies of octane-carboxamide based renin inhibitors with extended segments toward S3' site of renin.
abstract: Eighteen octane-carboxamide based renin inhibitors with extended segments for mimicking P3' unit of angiotensinogen have been synthesized. The biological evaluation identified novel renin inhibitors with more potent activity than aliskiren. Molecular docking studies showed that the extended amide-tails matched the P3' position of angiotensinogen and exerted interactions with the S3' site of renin. An unexpected π-π stacking interaction was observed during docking study for compound 9r, which could be a reasonable explanation for the outstanding potency of this compound. Further study is in progress to reveal a feasibility for developing novel renin inhibitors based on the possible non-classical interactions between the ligands and the new subsite of renin.
authors.affiliation: Center for Drug Discovery, College of Pharmacy, China Pharmaceutical University, 24 Tongjia Xiang, Nanjing 210009, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Wu
authors.forename: Chen
authors.initials: C
authors.lastname: Shi
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Sun
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Wu
authors.forename: Hongbin
authors.initials: H
authors.lastname: Sun
mesh_terms: D000577:Amides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D008024:Ligands; D008958:Models, Molecular; D008968:Molecular Conformation; D009795:Octanes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D012084:Renin-Angiotensin System / Q000187:drug effects; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D000092502:Renin Inhibitors
chemical_list: D000577:Amides; D000806:Angiotensin-Converting Enzyme Inhibitors; D008024:Ligands; D009795:Octanes; D000092502:Renin Inhibitors; C026728:octane