title: Design of non-nucleoside inhibitors of HIV-1 reverse transcriptase with improved drug resistance properties. 2.
abstract: HIV-1 nonnucleoside reverse transcriptase inhibitors (NNRTIs) are part of the combination therapy currently used to treat HIV infection. The features of a new NNRTI drug for HIV treatment must include selective potent activity against both wild-type virus as well as against mutant virus that have been selected by use of current antiretroviral treatment regimens. Based on analogy with known HIV-1 NNRTI inhibitors and modeling studies utilizing the X-ray crystal structure of inhibitors bound in the HIV-1 RT, a series of substituted 2-quinolones was synthesized and evaluated as HIV-1 inhibitors.
authors.affiliation: GlaxoSmithKline Research and Development, 5 Moore Drive, Research Triangle Park, North Carolina 27709, USA. Andy.A.Freeman@gsk.com
authors.forename: George A
authors.initials: GA
authors.lastname: Freeman
authors.forename: C Webster
authors.initials: CW
authors.lastname: Andrews Iii
authors.forename: Andrew L
authors.initials: AL
authors.lastname: Hopkins
authors.forename: Gina S
authors.initials: GS
authors.lastname: Lowell
authors.forename: Lee T
authors.initials: LT
authors.lastname: Schaller
authors.forename: Jill R
authors.initials: JR
authors.lastname: Cowan
authors.forename: Stephen S
authors.initials: SS
authors.lastname: Gonzales
authors.forename: George W
authors.initials: GW
authors.lastname: Koszalka
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Hazen
authors.forename: Lawrence R
authors.initials: LR
authors.lastname: Boone
authors.forename: Rob G
authors.initials: RG
authors.lastname: Ferris
authors.forename: Katrina L
authors.initials: KL
authors.lastname: Creech
authors.forename: Grace B
authors.initials: GB
authors.lastname: Roberts
authors.forename: Steven A
authors.initials: SA
authors.lastname: Short
authors.forename: Kurt
authors.initials: K
authors.lastname: Weaver
authors.forename: David J
authors.initials: DJ
authors.lastname: Reynolds
authors.forename: John
authors.initials: J
authors.lastname: Milton
authors.forename: Jingshan
authors.initials: J
authors.lastname: Ren
authors.forename: David I
authors.initials: DI
authors.lastname: Stuart
authors.forename: David K
authors.initials: DK
authors.lastname: Stammers
authors.forename: Joseph H
authors.initials: JH
authors.lastname: Chan
mesh_terms: D000480:Alkynes; D019380:Anti-HIV Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D048588:Benzoxazines; D001665:Binding Sites; D002460:Cell Line; D018360:Crystallography, X-Ray; D003521:Cyclopropanes; D015195:Drug Design; D024882:Drug Resistance, Viral; D054303:HIV Reverse Transcriptase / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D015497:HIV-1 / Q000187:drug effects / Q000201:enzymology; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D009154:Mutation; D010078:Oxazines / Q000737:chemistry; D015363:Quinolones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D018894:Reverse Transcriptase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D000480:Alkynes; D019380:Anti-HIV Agents; D048588:Benzoxazines; D003521:Cyclopropanes; D010078:Oxazines; D015363:Quinolones; D018894:Reverse Transcriptase Inhibitors; D054303:HIV Reverse Transcriptase; C098320:efavirenz