title: Design, synthesis and antiviral efficacy of a series of potent chloropyridyl ester-derived SARS-CoV 3CLpro inhibitors.
abstract: Design, synthesis and biological evaluation of a series of 5-chloropyridine ester-derived severe acute respiratory syndrome-coronavirus chymotrypsin-like protease inhibitors is described. Position of the carboxylate functionality is critical to potency. Inhibitor 10 with a 5-chloropyridinyl ester at position 4 of the indole ring is the most potent inhibitor with a SARS-CoV 3CLpro IC(50) value of 30 nM and an antiviral EC(50) value of 6.9 microM. Molecular docking studies have provided possible binding modes of these inhibitors.
authors.affiliation: Department of Chemistry, Purdue University, 560 Oval drive, West Lafayette, IN 47907, USA. akghosh@purdue.edu
authors.forename: Arun K
authors.initials: AK
authors.lastname: Ghosh
authors.forename: Gangli
authors.initials: G
authors.lastname: Gong
authors.forename: Valerie
authors.initials: V
authors.lastname: Grum-Tokars
authors.forename: Debbie C
authors.initials: DC
authors.lastname: Mulhearn
authors.forename: Susan C
authors.initials: SC
authors.lastname: Baker
authors.forename: Melissa
authors.initials: M
authors.lastname: Coughlin
authors.forename: Bellur S
authors.initials: BS
authors.lastname: Prabhakar
authors.forename: Katrina
authors.initials: K
authors.lastname: Sleeman
authors.forename: Michael E
authors.initials: ME
authors.lastname: Johnson
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Mesecar
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D020134:Catalytic Domain; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D000086782:Coronavirus 3C Proteases; D003546:Cysteine Endopeptidases / Q000737:chemistry; D015195:Drug Design; D004952:Esters; D006801:Humans; D020128:Inhibitory Concentration 50; D008956:Models, Chemical; D008958:Models, Molecular; D008968:Molecular Conformation; D011485:Protein Binding; D045473:Severe acute respiratory syndrome-related coronavirus / Q000378:metabolism*; D014764:Viral Proteins / Q000037:antagonists & inhibitors*
chemical_list: D000998:Antiviral Agents; D004952:Esters; D014764:Viral Proteins; D003546:Cysteine Endopeptidases; D000086782:Coronavirus 3C Proteases
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