title: Identification of a novel series of potent HCV NS5B Site I inhibitors.
abstract: Efforts investigating spatially comparative alternates of the ethylene-bridged piperazine in BMS-791325 that would offer a maintained or improved virologic and pharmacokinetic profile have been multifaceted. One foray involved the utilization of various octahydropyrrolo[3,4-c]pyrrole propellanes. Many of the propellane analogs described in this work exhibited better than targeted potency (less than 20 nM). Additionally, improved exposure in rats was achieved through the employment of two newly invented and now readily accessible carbon bridged propellanes as compared to their heteroatom bridged analogs.
authors.affiliation: Research and Development, Bristol-Myers Squibb Company, 5 Research Parkway, Wallingford, CT 06492, USA. Electronic address: kyle.eastman@bms.com.
authors.forename: Kyle J
authors.initials: KJ
authors.lastname: Eastman
authors.affiliation: Research and Development, Bristol-Myers Squibb Company, 5 Research Parkway, Wallingford, CT 06492, USA.
authors.forename: Zhong
authors.initials: Z
authors.lastname: Yang
authors.affiliation: Research and Development, Bristol-Myers Squibb Company, 5 Research Parkway, Wallingford, CT 06492, USA.
authors.forename: John A
authors.initials: JA
authors.lastname: Bender
authors.affiliation: Research and Development, Bristol-Myers Squibb Company, 5 Research Parkway, Wallingford, CT 06492, USA.
authors.forename: Kathy
authors.initials: K
authors.lastname: Mosure
authors.affiliation: Research and Development, Bristol-Myers Squibb Company, 5 Research Parkway, Wallingford, CT 06492, USA.
authors.forename: Julie A
authors.initials: JA
authors.lastname: Lemm
authors.affiliation: Research and Development, Bristol-Myers Squibb Company, 5 Research Parkway, Wallingford, CT 06492, USA.
authors.forename: Nicholas A
authors.initials: NA
authors.lastname: Meanwell
authors.affiliation: Research and Development, Bristol-Myers Squibb Company, 5 Research Parkway, Wallingford, CT 06492, USA.
authors.forename: Susan B
authors.initials: SB
authors.lastname: Roberts
authors.affiliation: Research and Development, Bristol-Myers Squibb Company, 5 Research Parkway, Wallingford, CT 06492, USA.
authors.forename: Jay
authors.initials: J
authors.lastname: Knipe
authors.affiliation: Research and Development, Bristol-Myers Squibb Company, 5 Research Parkway, Wallingford, CT 06492, USA.
authors.forename: John F
authors.initials: JF
authors.lastname: Kadow
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000737:chemistry* / Q000493:pharmacokinetics*; D001552:Benzazepines / Q000737:chemistry; D016174:Hepacivirus; D007211:Indoles / Q000737:chemistry; D015394:Molecular Structure; D051381:Rats; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors*; D012324:RNA-Dependent RNA Polymerase
chemical_list: D000998:Antiviral Agents; D001552:Benzazepines; D007211:Indoles; D017361:Viral Nonstructural Proteins; C587012:8-cyclohexyl-N-((dimethylamino)sulfonyl)-1,1a,2,12b-tetrahydro-11-methoxy-1a-((3-methyl-3,8-diazabicyclo(3.2.1)oct-8-yl)carbonyl)cycloprop(d)indolo(2,1-a)(2)benzazepine-5-carboxamide; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase
keywords: HCV; Hepatitis; NS5B; Propellane; Site I