title: Azetidines and spiro azetidines as novel P2 units in hepatitis C virus NS3 protease inhibitors.
abstract: Herein, we report the synthesis and structure-activity relationship studies of new analogs of boceprevir 1 and telaprevir 2. Introduction of azetidine and spiroazetidines as a P2 substituent that replaced the pyrrolidine moiety of 1 and 2 led to the discovery of a potent hepatitis C protease inhibitor 37c (EC50=0.8 μM).
authors.affiliation: Center for AIDS Research, Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine, Veterans Affairs Medical Center, 1670 Haygood Drive, NE, Atlanta, GA 30322, USA.
authors.forename: Lavanya
authors.initials: L
authors.lastname: Bondada
authors.forename: Ramu
authors.initials: R
authors.lastname: Rondla
authors.forename: Ugo
authors.initials: U
authors.lastname: Pradere
authors.forename: Peng
authors.initials: P
authors.lastname: Liu
authors.forename: Chengwei
authors.initials: C
authors.lastname: Li
authors.forename: Drew
authors.initials: D
authors.lastname: Bobeck
authors.forename: Tamara
authors.initials: T
authors.lastname: McBrayer
authors.forename: Philip
authors.initials: P
authors.lastname: Tharnish
authors.forename: Jerome
authors.initials: J
authors.lastname: Courcambeck
authors.forename: Philippe
authors.initials: P
authors.lastname: Halfon
authors.forename: Tony
authors.initials: T
authors.lastname: Whitaker
authors.forename: Franck
authors.initials: F
authors.lastname: Amblard
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Coats
authors.forename: Raymond F
authors.initials: RF
authors.lastname: Schinazi
mesh_terms: D000998:Antiviral Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001384:Azetidines / Q000737:chemistry* / Q000494:pharmacology*; D015195:Drug Design; D006526:Hepatitis C / Q000188:drug therapy*; D006801:Humans; D008958:Models, Molecular; D011480:Protease Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry*; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases
chemical_list: D000998:Antiviral Agents; D001384:Azetidines; D011480:Protease Inhibitors; 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: Antiviral; HCV; Protease inhibitor