title: Picomolar Inhibitors of HIV-1 Reverse Transcriptase: Design and Crystallography of Naphthyl Phenyl Ethers.
abstract: Catechol diethers that incorporate a 6-cyano-1-naphthyl substituent have been explored as non-nucleoside inhibitors of HIV-1 reverse transcriptase (NNRTIs). Promising compounds are reported that show midpicomolar activity against the wild-type virus and sub-20 nM activity against viral variants bearing Tyr181Cys and Lys103Asn mutations in HIV-RT. An X-ray crystal structure at 2.49 Å resolution is also reported for the key compound 6e with HIV-RT.
authors.affiliation: Department of Chemistry, Yale University , New Haven, Connecticut 06520-8107, United States.
authors.forename: Won-Gil
authors.initials: WG
authors.lastname: Lee
authors.affiliation: Department of Pharmacology, Yale University School of Medicine , New Haven, Connecticut 06520-8066, United States.
authors.forename: Kathleen M
authors.initials: KM
authors.lastname: Frey
authors.affiliation: Department of Chemistry, Yale University , New Haven, Connecticut 06520-8107, United States.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Gallardo-Macias
authors.affiliation: Department of Pharmacology, Yale University School of Medicine , New Haven, Connecticut 06520-8066, United States.
authors.forename: Krasimir A
authors.initials: KA
authors.lastname: Spasov
authors.affiliation: Department of Chemistry, Yale University , New Haven, Connecticut 06520-8107, United States.
authors.forename: Mariela
authors.initials: M
authors.lastname: Bollini
authors.affiliation: Department of Pharmacology, Yale University School of Medicine , New Haven, Connecticut 06520-8066, United States.
authors.forename: Karen S
authors.initials: KS
authors.lastname: Anderson
authors.affiliation: Department of Chemistry, Yale University , New Haven, Connecticut 06520-8107, United States.
authors.forename: William L
authors.initials: WL
authors.lastname: Jorgensen
keywords: Anti-HIV agents; NNRTIs; protein crystallography