Synthesis of alkenyldiarylmethane (ADAM) non-nucleoside HIV-1 reverse transcriptase inhibitors with non-identical aromatic rings.
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.
Xu
Guozhang
G
Department of Medicinal Chemistry and Molecular Pharmacology, School of Pharmacy and Pharmacal Sciences, Purdue University, West Lafayette, IN 47907, USA.
Hartman
Tracy L
TL
Wargo
Heather
H
Turpin
Jim A
JA
Buckheit
Robert W
RW
Cushman
Mark
M
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
D006841:Hydrocarbons, Aromatic; D018894:Reverse Transcriptase Inhibitors; D054303:HIV Reverse Transcriptase