title: Inhibitors of HCV NS5B polymerase. Part 1: Evaluation of the southern region of (2Z)-2-(benzoylamino)-3-(5-phenyl-2-furyl)acrylic acid.
abstract: A novel series of nonnucleoside HCV NS5B polymerase inhibitors were prepared from (2Z)-2-(benzoylamino)-3-(5-phenyl-2-furyl)acrylic acid, a high throughput screening lead. SAR studies combined with structure based drug design focusing on the southern heterobiaryl region of the template led to the synthesis of several potent and orally bioavailable lead compounds. X-ray crystallography studies were also performed to understand the interaction of these inhibitors with HCV NS5B polymerase.
authors.affiliation: Pfizer Global Research and Development, Michigan Laboratories, 2800 Plymouth Road, Ann Arbor, MI 48105, USA. jeffrey.a.pfefferkorn@pfizer.com
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Pfefferkorn
authors.forename: Meredith L
authors.initials: ML
authors.lastname: Greene
authors.forename: Richard A
authors.initials: RA
authors.lastname: Nugent
authors.forename: Rebecca J
authors.initials: RJ
authors.lastname: Gross
authors.forename: Mark A
authors.initials: MA
authors.lastname: Mitchell
authors.forename: Barry C
authors.initials: BC
authors.lastname: Finzel
authors.forename: Melissa S
authors.initials: MS
authors.lastname: Harris
authors.forename: Peter A
authors.initials: PA
authors.lastname: Wells
authors.forename: John A
authors.initials: JA
authors.lastname: Shelly
authors.forename: Robert A
authors.initials: RA
authors.lastname: Anstadt
authors.forename: Robert E
authors.initials: RE
authors.lastname: Kilkuskie
authors.forename: Laurice A
authors.initials: LA
authors.lastname: Kopta
authors.forename: Francis J
authors.initials: FJ
authors.lastname: Schwende
mesh_terms: D000179:Acrylates / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D001682:Biological Availability; D018360:Crystallography, X-Ray; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D005663:Furans / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors*; D012324:RNA-Dependent RNA Polymerase
chemical_list: D000179:Acrylates; D004791:Enzyme Inhibitors; D005663:Furans; D017361:Viral Nonstructural Proteins; C504279:(2Z)-2-(benzoylamino)-3-(5-phenyl-2-furyl)acrylic acid; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase; C036658:acrylic acid