title: Design and synthesis of pyridone inhibitors of non-nucleoside reverse transcriptase.
abstract: Next generation NNRTIs are sought which possess both broad spectrum antiviral activity against key mutant strains and a high genetic barrier to the selection of new mutant viral strains. Pyridones were evaluated as an acyclic conformational constraint to replace the aryl ether core of MK-4965 (1) and the more rigid indazole constraint of MK-6186 (2). The resulting pyridone compounds are potent inhibitors of HIV RT and have antiviral activity in cell culture that is superior to other next generation NNRTI's.
authors.affiliation: Department of West Point Discovery Chemistry, Merck Research Labs., 770 Sumneytown Pike, PO Box 4, West Point, PA 19486-0004, USA. Robert_gomez@merck.com
authors.forename: Robert
authors.initials: R
authors.lastname: Gomez
authors.forename: Samson
authors.initials: S
authors.lastname: Jolly
authors.forename: Theresa
authors.initials: T
authors.lastname: Williams
authors.forename: Thomas
authors.initials: T
authors.lastname: Tucker
authors.forename: Robert
authors.initials: R
authors.lastname: Tynebor
authors.forename: Joe
authors.initials: J
authors.lastname: Vacca
authors.forename: Georgia
authors.initials: G
authors.lastname: McGaughey
authors.forename: Ming-Tain
authors.initials: MT
authors.lastname: Lai
authors.forename: Peter
authors.initials: P
authors.lastname: Felock
authors.forename: Vandna
authors.initials: V
authors.lastname: Munshi
authors.forename: Daniel
authors.initials: D
authors.lastname: DeStefano
authors.forename: Sinoeun
authors.initials: S
authors.lastname: Touch
authors.forename: Mike
authors.initials: M
authors.lastname: Miller
authors.forename: Youwei
authors.initials: Y
authors.lastname: Yan
authors.forename: Rosa
authors.initials: R
authors.lastname: Sanchez
authors.forename: Yuexia
authors.initials: Y
authors.lastname: Liang
authors.forename: Brenda
authors.initials: B
authors.lastname: Paton
authors.forename: Bang-Lin
authors.initials: BL
authors.lastname: Wan
authors.forename: Neville
authors.initials: N
authors.lastname: Anthony
mesh_terms: D001665:Binding Sites; D002460:Cell Line; D003198:Computer Simulation; D015195:Drug Design; D004789:Enzyme Activation / Q000187:drug effects; D006678:HIV / Q000201:enzymology; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D017434:Protein Structure, Tertiary; D011720:Pyrazoles / Q000737:chemistry; D011725:Pyridines / Q000737:chemistry; D011728:Pyridones / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D018894:Reverse Transcriptase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
chemical_list: C532853:3-(5-((6-amino-1H-pyrazolo(3,4-b)pyridine-3-yl)methoxy)-2-chlorophenoxy)-5-chlorobenzonitrile; D011720:Pyrazoles; D011725:Pyridines; D011728:Pyridones; D018894:Reverse Transcriptase Inhibitors; D054303:HIV Reverse Transcriptase