title: Novel, sulfonamide linked inhibitors of the hepatitis C virus NS3 protease.
abstract: A sulfonamide replacement of the P2-P3 amide bond in the context of macrocyclic HCV NS3 protease inhibitors was investigated. These analogs displayed good inhibitory potency in the absence of any P3 capping group. The synthesis and preliminary SAR are described.
authors.affiliation: Gilead Sciences, Inc., Department of Medicinal Chemistry, 333 Lakeside Dr, Foster City, CA 94404, USA. Electronic address: tkirschberg@gilead.com.
authors.forename: Thorsten A
authors.initials: TA
authors.lastname: Kirschberg
authors.affiliation: Gilead Sciences, Inc., Department of Medicinal Chemistry, 333 Lakeside Dr, Foster City, CA 94404, USA.
authors.forename: Neil H
authors.initials: NH
authors.lastname: Squires
authors.affiliation: Gilead Sciences, Inc., Department of Biology, 333 Lakeside Dr, Foster City, CA 94404, USA.
authors.forename: Huiling
authors.initials: H
authors.lastname: Yang
authors.affiliation: Gilead Sciences, Inc., Department of Biology, 333 Lakeside Dr, Foster City, CA 94404, USA.
authors.forename: Amoreena C
authors.initials: AC
authors.lastname: Corsa
authors.affiliation: Gilead Sciences, Inc., Department of Biology, 333 Lakeside Dr, Foster City, CA 94404, USA.
authors.forename: Yang
authors.initials: Y
authors.lastname: Tian
authors.affiliation: Gilead Sciences, Inc., Department of Biology, 333 Lakeside Dr, Foster City, CA 94404, USA.
authors.forename: Neeraj
authors.initials: N
authors.lastname: Tirunagari
authors.affiliation: Gilead Sciences, Inc., Department of Medicinal Chemistry, 333 Lakeside Dr, Foster City, CA 94404, USA.
authors.forename: X Christopher
authors.initials: XC
authors.lastname: Sheng
authors.affiliation: Gilead Sciences, Inc., Department of Medicinal Chemistry, 333 Lakeside Dr, Foster City, CA 94404, USA; Kainos Medicine, Inc., 88, Olympic-ro 43-gil, Seoul 138-736, Republic of Korea.
authors.forename: Choung U
authors.initials: CU
authors.lastname: Kim
mesh_terms: D004789:Enzyme Activation / Q000187:drug effects; D016174:Hepacivirus / Q000187:drug effects*; D006801:Humans; D020128:Inhibitory Concentration 50; D015394:Molecular Structure; D011480:Protease Inhibitors / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000737:chemistry* / Q000494:pharmacology; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors*; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases
chemical_list: D011480:Protease Inhibitors; D013449:Sulfonamides; D017361:Viral Nonstructural Proteins; C084422:NS3 protein, hepatitis C virus; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases
keywords: HCV; NS3 protease; Sulfonamide