title: Discovery of novel tricyclic indole derived inhibitors of HCV NS5B RNA dependent RNA polymerase.
abstract: The characterization of HCV genome has identified various vital functional proteins involved in the life cycle of hepatitis C virus. This has resulted in many novel enzymatic targets that are potential for development of therapeutic agents. The HCV RNA dependent RNA polymerase (HCV NS5B) is one such essential enzyme for HCV replication that has been well characterized and studied by various groups to develop novel therapies for hepatitis C. In this paper, we describe our efforts towards the identification and structure-activity relationship (SAR) of novel tricyclic indole derivatives that bind close to the palm site of the NS5B polymerase. X-ray crystal structure of an inhibitor bound to the polymerase is also described.
authors: Merck Research Laboratories, Mail Stop RY121E-28, 126 East Lincoln Avenue, Rahway, NJ 07065-0900, USA. Srikanth.Venkatraman@merck.com
authors: Srikanth
authors: S
authors: Venkatraman
authors: Francisco
authors: F
authors: Velazquez
authors: Stephen
authors: S
authors: Gavalas
authors: Wanli
authors: W
authors: Wu
authors: Kevin X
authors: KX
authors: Chen
authors: Anilkumar G
authors: AG
authors: Nair
authors: Frank
authors: F
authors: Bennett
authors: Yuhua
authors: Y
authors: Huang
authors: Patrick
authors: P
authors: Pinto
authors: Yueheng
authors: Y
authors: Jiang
authors: Oleg
authors: O
authors: Selyutin
authors: Bancha
authors: B
authors: Vibulbhan
authors: Qingbei
authors: Q
authors: Zeng
authors: Charles
authors: C
authors: Lesburg
authors: Jose
authors: J
authors: Duca
authors: Hsueh-Cheng
authors: HC
authors: Huang
authors: Sony
authors: S
authors: Agrawal
authors: Chuan-kui
authors: CK
authors: Jiang
authors: Eric
authors: E
authors: Ferrari
authors: Cheng
authors: C
authors: Li
authors: Joseph
authors: J
authors: Kozlowski
authors: Stuart
authors: S
authors: Rosenblum
authors: Neng-Yang
authors: NY
authors: Shih
authors: F George
authors: FG
authors: Njoroge
mesh_terms: D000998:Antiviral Agents / Q000737:chemistry* / Q000494:pharmacology*; D001665:Binding Sites; D018360:Crystallography, X-Ray; D016174:Hepacivirus / Q000737:chemistry / Q000201:enzymology*; D006526:Hepatitis C / Q000188:drug therapy / Q000821:virology; D006801:Humans; D007211:Indoles / Q000737:chemistry* / Q000494:pharmacology*; D062105:Molecular Docking Simulation; D012324:RNA-Dependent RNA Polymerase / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D000998:Antiviral Agents; D007211:Indoles; D012324:RNA-Dependent RNA Polymerase