title: Synthesis and SAR studies of novel heteroaryl fused tetracyclic indole-diamide compounds: potent allosteric inhibitors of the hepatitis C virus NS5B polymerase.
abstract: Presented here are initial structure-activity relationship (SAR) studies on a series of novel heteroaryl fused tetracyclic indole-based inhibitors of the hepatitis C viral polymerase, NS5B. The introduction of alternative heterocyclic moieties into the indolo-fused inhibitor class significantly expands the reported SAR and resulted in the identification of pyridino analogs, typified by compounds 44 and 45 that displayed excellent potency against the NS5B polymerase of both HCV 1a and HCV 1b genotypes.
authors.affiliation: Molecular Sciences and Candidate Optimization, Bristol-Myers Squibb, Research and Development, Wallingford, CT 06492, United States. min.ding@bms.com
authors.forename: Min
authors.initials: M
authors.lastname: Ding
authors.forename: Feng
authors.initials: F
authors.lastname: He
authors.forename: Thomas W
authors.initials: TW
authors.lastname: Hudyma
authors.forename: Xiaofan
authors.initials: X
authors.lastname: Zheng
authors.forename: Michael A
authors.initials: MA
authors.lastname: Poss
authors.forename: John F
authors.initials: JF
authors.lastname: Kadow
authors.forename: Brett R
authors.initials: BR
authors.lastname: Beno
authors.forename: Karen L
authors.initials: KL
authors.lastname: Rigat
authors.forename: Ying-Kai
authors.initials: YK
authors.lastname: Wang
authors.forename: Robert A
authors.initials: RA
authors.lastname: Fridell
authors.forename: Julie A
authors.initials: JA
authors.lastname: Lemm
authors.forename: Dike
authors.initials: D
authors.lastname: Qiu
authors.forename: Mengping
authors.initials: M
authors.lastname: Liu
authors.forename: Stacey
authors.initials: S
authors.lastname: Voss
authors.forename: Lenore A
authors.initials: LA
authors.lastname: Pelosi
authors.forename: Susan B
authors.initials: SB
authors.lastname: Roberts
authors.forename: Min
authors.initials: M
authors.lastname: Gao
authors.forename: Jay
authors.initials: J
authors.lastname: Knipe
authors.forename: Robert G
authors.initials: RG
authors.lastname: Gentles
mesh_terms: D000494:Allosteric Regulation; D000577:Amides / Q000737:chemistry* / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology; D016174:Hepacivirus / Q000187:drug effects*; D006571:Heterocyclic Compounds / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology; D006801:Humans; D007211:Indoles / Q000737:chemistry / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D013329:Structure-Activity Relationship; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors*; D012324:RNA-Dependent RNA Polymerase
chemical_list: D000577:Amides; D004791:Enzyme Inhibitors; D006571:Heterocyclic Compounds; D007211:Indoles; D017361:Viral Nonstructural Proteins; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase