title: Biaryl ethers as potent allosteric inhibitors of reverse transcriptase and its key mutant viruses: aryl substituted pyrazole as a surrogate for the pyrazolopyridine motif.
abstract: Biaryl ethers were recently reported as potent NNRTIs. Herein, we disclose a detailed effort to modify the previously reported compound 1. We have designed and synthesized a series of novel pyrazole derivatives as a surrogate for pyrazolopyridine motif that were potent inhibitors of HIV-1 RT with nanomolar intrinsic activity on the WT and key mutant enzymes and potent antiviral activity in infected cells.
authors.affiliation: Department of Medicinal Chemistry and Structural Biology, Merck Research Laboratory, West Point, PA 19486, USA.
authors.forename: Dai-Shi
authors.initials: DS
authors.lastname: Su
authors.forename: John J
authors.initials: JJ
authors.lastname: Lim
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Tinney
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Tucker
authors.forename: Sandeep
authors.initials: S
authors.lastname: Saggar
authors.forename: John T
authors.initials: JT
authors.lastname: Sisko
authors.forename: Bang-Lin
authors.initials: BL
authors.lastname: Wan
authors.forename: Mary Beth
authors.initials: MB
authors.lastname: Young
authors.forename: Kenneth D
authors.initials: KD
authors.lastname: Anderson
authors.forename: Deanne
authors.initials: D
authors.lastname: Rudd
authors.forename: Vandna
authors.initials: V
authors.lastname: Munshi
authors.forename: Carolyn
authors.initials: C
authors.lastname: Bahnck
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Felock
authors.forename: Meiquing
authors.initials: M
authors.lastname: Lu
authors.forename: Ming-Tain
authors.initials: MT
authors.lastname: Lai
authors.forename: Sinoeun
authors.initials: S
authors.lastname: Touch
authors.forename: Gregory
authors.initials: G
authors.lastname: Moyer
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Distefano
authors.forename: Jessica A
authors.initials: JA
authors.lastname: Flynn
authors.forename: Yuexia
authors.initials: Y
authors.lastname: Liang
authors.forename: Rosa
authors.initials: R
authors.lastname: Sanchez
authors.forename: Rebecca
authors.initials: R
authors.lastname: Perlow-Poehnelt
authors.forename: Mike
authors.initials: M
authors.lastname: Miller
authors.forename: Joe P
authors.initials: JP
authors.lastname: Vacca
authors.forename: Theresa M
authors.initials: TM
authors.lastname: Williams
authors.forename: Neville J
authors.initials: NJ
authors.lastname: Anthony
mesh_terms: D000494:Allosteric Regulation; D000818:Animals; D019380:Anti-HIV Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D004285:Dogs; D004987:Ethers / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D009154:Mutation; D011720:Pyrazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D011725:Pyridines / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D051381:Rats; D018894:Reverse Transcriptase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D013329:Structure-Activity Relationship
chemical_list: D019380:Anti-HIV Agents; D004987:Ethers; D011720:Pyrazoles; D011725:Pyridines; D018894:Reverse Transcriptase Inhibitors; C118531:pyrazolopyridine; C514824:reverse transcriptase, Human immunodeficiency virus 1; D054303:HIV Reverse Transcriptase