title: HCV NS5A replication complex inhibitors. Part 4. Optimization for genotype 1a replicon inhibitory activity.
abstract: A series of symmetrical E-stilbene prolinamides that originated from the library-synthesized lead 3 was studied with respect to HCV genotype 1a (G-1a) and genotype 1b (G-1b) replicon inhibition and selectivity against BVDV and cytotoxicity. SAR emerging from an examination of the prolinamide cap region revealed 11 to be a selective HCV NS5A inhibitor exhibiting submicromolar potency against both G-1a and G-1b replicons. Additional structural refinements resulted in the identification of 30 as a potent, dual G-1a/1b HCV NS5A inhibitor.
authors.affiliation: Departments of †Medicinal Chemistry, ‡Virology, and §Computer-Aided Drug Design, Bristol-Myers Squibb Research and Development , 5 Research Parkway, Wallingford, Connecticut 06492, United States.
authors.forename: Denis R
authors.initials: DR
authors.lastname: St Laurent
authors.forename: Michael H
authors.initials: MH
authors.lastname: Serrano-Wu
authors.forename: Makonen
authors.initials: M
authors.lastname: Belema
authors.forename: Min
authors.initials: M
authors.lastname: Ding
authors.forename: Hua
authors.initials: H
authors.lastname: Fang
authors.forename: Min
authors.initials: M
authors.lastname: Gao
authors.forename: Jason T
authors.initials: JT
authors.lastname: Goodrich
authors.forename: Rudolph G
authors.initials: RG
authors.lastname: Krause
authors.forename: Julie A
authors.initials: JA
authors.lastname: Lemm
authors.forename: Mengping
authors.initials: M
authors.lastname: Liu
authors.forename: Omar D
authors.initials: OD
authors.lastname: Lopez
authors.forename: Van N
authors.initials: VN
authors.lastname: Nguyen
authors.forename: Peter T
authors.initials: PT
authors.lastname: Nower
authors.forename: Donald R
authors.initials: DR
authors.lastname: O'Boyle
authors.forename: Bradley C
authors.initials: BC
authors.lastname: Pearce
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Romine
authors.forename: Lourdes
authors.initials: L
authors.lastname: Valera
authors.forename: Jin-Hua
authors.initials: JH
authors.lastname: Sun
authors.forename: Ying-Kai
authors.initials: YK
authors.lastname: Wang
authors.forename: Fukang
authors.initials: F
authors.lastname: Yang
authors.forename: Xuejie
authors.initials: X
authors.lastname: Yang
authors.forename: Nicholas A
authors.initials: NA
authors.lastname: Meanwell
authors.forename: Lawrence B
authors.initials: LB
authors.lastname: Snyder
mesh_terms: D000998:Antiviral Agents / Q000737:chemistry / Q000494:pharmacology*; D005838:Genotype; D016174:Hepacivirus / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D011480:Protease Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D012324:RNA-Dependent RNA Polymerase / Q000037:antagonists & inhibitors*; D012093:Replicon / Q000187:drug effects*; D021241:Spectrometry, Mass, Electrospray Ionization; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors*; D014779:Virus Replication / Q000187:drug effects*
chemical_list: D000998:Antiviral Agents; D011480:Protease Inhibitors; D017361:Viral Nonstructural Proteins; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase