title: Identification of a new biaryl scaffold generating potent renin inhibitors.
abstract: The discovery and SAR of a series of potent renin inhibitors possessing a novel biaryl scaffold are described herein. Molecular modeling revealed that the cyclopropylamide spacer present in 1 can be replaced by a simple, substituted aromatic ring such as a toluene in 2. The resulting compounds exhibit subnanomolar renin IC(50) and good oral bioavailability in rats.
authors: Merck Frosst Center for Therapeutic Research, PO Box 1005, Pointe Claire-Dorval, Québec, Canada.
authors: Patrick
authors: P
authors: Lacombe
authors: Renée
authors: R
authors: Aspiotis
authors: Christopher
authors: C
authors: Bayly
authors: Austin
authors: A
authors: Chen
authors: Daniel
authors: D
authors: Dubé
authors: Réjean
authors: R
authors: Fortin
authors: Michel
authors: M
authors: Gallant
authors: Hélène
authors: H
authors: Juteau
authors: Suzanna
authors: S
authors: Liu
authors: Dan
authors: D
authors: McKay
authors: Patrick
authors: P
authors: Roy
authors: Tom
authors: T
authors: Wu
mesh_terms: D000284:Administration, Oral; D000577:Amides / Q000737:chemistry; D000818:Animals; D001632:Bibenzyls / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D051381:Rats; D012083:Renin / Q000378:metabolism; D013329:Structure-Activity Relationship; D000092502:Renin Inhibitors
chemical_list: D000577:Amides; D001632:Bibenzyls; D004791:Enzyme Inhibitors; D012083:Renin; D000092502:Renin Inhibitors