title: Benzophenone derivatives: a novel series of potent and selective inhibitors of human immunodeficiency virus type 1 reverse transcriptase.
abstract: A series of benzophenone derivatives has been synthesized and evaluated as inhibitors of HIV-1 reverse transcriptase (RT) and the growth of HIV-1 in MT-4 cells. Through the use of the structure-activity relationships within this series of compounds and computational chemistry techniques, a binding conformation is proposed. The SAR also indicated that the major interactions of 1h with the RT enzyme are through hydrogen bonding of the amide and benzophenone carbonyls and pi-orbital interactions with the benzophenone nucleus and an aromatic function separated from the benzophenone by a suitable spacer group. The crystal structure of compound 1h has been determined. A number of compounds with potent inhibitory activity against HIV-1 RT and HIV in cellular assays at levels comparable with AZT and our efforts to identify a metabolically stable analogue are described.
authors.affiliation: Medicinal Chemistry Department, Glaxo Research and Development Limited, Glaxo Medicines Research Centre, Stevenage, Herts, U.K.
authors.forename: P G
authors.initials: PG
authors.lastname: Wyatt
authors.forename: R C
authors.initials: RC
authors.lastname: Bethell
authors.forename: N
authors.initials: N
authors.lastname: Cammack
authors.forename: D
authors.initials: D
authors.lastname: Charon
authors.forename: N
authors.initials: N
authors.lastname: Dodic
authors.forename: B
authors.initials: B
authors.lastname: Dumaitre
authors.forename: D N
authors.initials: DN
authors.lastname: Evans
authors.forename: D V
authors.initials: DV
authors.lastname: Green
authors.forename: P L
authors.initials: PL
authors.lastname: Hopewell
authors.forename: D C
authors.initials: DC
authors.lastname: Humber
mesh_terms: D001577:Benzophenones / Q000494:pharmacology*; D002460:Cell Line; D018360:Crystallography, X-Ray; D004352:Drug Resistance, Microbial; D054303:HIV Reverse Transcriptase; D015497:HIV-1 / Q000187:drug effects / Q000201:enzymology*; D018894:Reverse Transcriptase Inhibitors; D013329:Structure-Activity Relationship
chemical_list: D001577:Benzophenones; D018894:Reverse Transcriptase Inhibitors; D054303:HIV Reverse Transcriptase