title: II. Novel HCV NS5B polymerase inhibitors: discovery of indole C2 acyl sulfonamides.
abstract: Development of SAR at the C2 position of indole lead 1, a palm site inhibitor of HCV NS5B polymerase (NS5B IC(50)=0.053μM, replicon EC(50)=4.8μM), is described. Initial screening identified an acyl sulfonamide moiety as an isostere for the C2 carboxylic acid group. Further SAR investigation resulted in identification of acyl sufonamide analog 7q (NS5B IC(50)=0.039μM, replicon EC(50)=0.011μM) with >100-fold improved replicon activity.
authors: Merck Research Laboratories, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA. gopinadhan.anilkumar@Merck.com
authors: Gopinadhan N
authors: GN
authors: Anilkumar
authors: Oleg
authors: O
authors: Selyutin
authors: Stuart B
authors: SB
authors: Rosenblum
authors: Qingbei
authors: Q
authors: Zeng
authors: Yueheng
authors: Y
authors: Jiang
authors: Tin-Yau
authors: TY
authors: Chan
authors: Haiyan
authors: H
authors: Pu
authors: Li
authors: L
authors: Wang
authors: Frank
authors: F
authors: Bennett
authors: Kevin X
authors: KX
authors: Chen
authors: Charles A
authors: CA
authors: Lesburg
authors: Jose
authors: J
authors: Duca
authors: Stephen
authors: S
authors: Gavalas
authors: Yuhua
authors: Y
authors: Huang
authors: Patrick
authors: P
authors: Pinto
authors: Mousumi
authors: M
authors: Sannigrahi
authors: Francisco
authors: F
authors: Velazquez
authors: Srikanth
authors: S
authors: Venkatraman
authors: Bancha
authors: B
authors: Vibulbhan
authors: Sony
authors: S
authors: Agrawal
authors: Eric
authors: E
authors: Ferrari
authors: Chuan-Kui
authors: CK
authors: Jiang
authors: H-C
authors: HC
authors: Huang
authors: Neng-Yang
authors: NY
authors: Shih
authors: F
authors: F
authors: George Njoroge
authors: Joseph A
authors: JA
authors: Kozlowski
mesh_terms: D000998:Antiviral Agents / Q000494:pharmacology*; D002626:Chemistry, Pharmaceutical / Q000379:methods; D018360:Crystallography, X-Ray / Q000379:methods; D015195:Drug Design; D006801:Humans; D006860:Hydrogen Bonding; D007211:Indoles / Q000737:chemistry*; D020128:Inhibitory Concentration 50; D008956:Models, Chemical; D008958:Models, Molecular; D008968:Molecular Conformation; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000737:chemistry; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors*; D012324:RNA-Dependent RNA Polymerase
chemical_list: D000998:Antiviral Agents; D007211:Indoles; D013449:Sulfonamides; D017361:Viral Nonstructural Proteins; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase