title: Biaryl ethers as novel non-nucleoside reverse transcriptase inhibitors with improved potency against key mutant viruses.
abstract: Biaryl ethers were recently reported as potent NNRTIs. Herein we disclose a detailed SAR study that led to the biaryl ether 6. This compound possessed excellent potency against WT RT and key clinically observed RT mutants and had an excellent pharmacokinetic profile in rats, dogs, and rhesus macaques. The compound also exhibited a clean safety profile in preclinical safety studies.
authors.affiliation: Department of Medicinal Chemistry and Structural Biology, Merck Research Laboratory, P.O. Box 4, West Point, Pennsylvania 19486, USA. Dai-Shi.X.Su@gsk.com
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: 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: D000818:Animals; D002460:Cell Line; D004285:Dogs; D004987:Ethers / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors* / Q000235:genetics*; D015497:HIV-1 / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics*; D006801:Humans; D008253:Macaca mulatta; D009154:Mutation; D009705:Nucleosides / Q000737:chemistry; D051381:Rats; D018894:Reverse Transcriptase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D004987:Ethers; D009705:Nucleosides; D018894:Reverse Transcriptase Inhibitors; D054303:HIV Reverse Transcriptase