title: Synthesis of alkenyldiarylmethane (ADAM) non-nucleoside HIV-1 reverse transcriptase inhibitors with non-identical aromatic rings.
abstract: The existing methods for the synthesis of alkenyldiarylmethane (ADAM) non-nucleoside reverse transcriptase inhibitors proceed from symmetrical benzophenones and therefore result in products with identical aromatic rings. New methods have therefore been devised for the preparation of stereochemically defined ADAMs with non-identical aromatic rings. The new routes rely on palladium-catalyzed reactions, including Sonogashira, Suzuki, Stille, and hydroarylation methodology. Several of the new ADAMs inhibited the cytopathic effect of HIV-1 in cell culture and HIV-1 reverse transcriptase at submicromolar concentrations.
authors.affiliation: Department of Medicinal Chemistry and Molecular Pharmacology, School of Pharmacy and Pharmacal Sciences, Purdue University, West Lafayette, IN 47907, USA.
authors.forename: Guozhang
authors.initials: G
authors.lastname: Xu
authors.forename: Tracy L
authors.initials: TL
authors.lastname: Hartman
authors.forename: Heather
authors.initials: H
authors.lastname: Wargo
authors.forename: Jim A
authors.initials: JA
authors.lastname: Turpin
authors.forename: Robert W
authors.initials: RW
authors.lastname: Buckheit
authors.forename: Mark
authors.initials: M
authors.lastname: Cushman
mesh_terms: D001671:Biochemistry / Q000379:methods*; D002478:Cells, Cultured; D004353:Drug Evaluation, Preclinical / Q000379:methods; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors*; D006801:Humans; D006841:Hydrocarbons, Aromatic / Q000737:chemistry; D020128:Inhibitory Concentration 50; D018894:Reverse Transcriptase Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D006841:Hydrocarbons, Aromatic; D018894:Reverse Transcriptase Inhibitors; D054303:HIV Reverse Transcriptase