Solid-phase synthesis of the alkenyldiarylmethane (ADAM) series of non-nucleoside HIV-1 reverse transcriptase inhibitors.
The Sonogashira and Stille cross-coupling reactions have been employed in the synthesis of several non-nucleoside reverse transcriptase inhibitors (NNRTIs) in the alkenyldiarylmethane (ADAM) series. The synthesis has been carried out both in solution and on a solid support. In contrast to previous syntheses of NNRTIs in the ADAM series, the present strategy allows the incorporation of differently substituted aromatic rings in a stereochemically defined fashion. The most potent of the new ADAMs inhibited the cytopathic effect of HIV-1RF in CEM-SS cell culture with an EC50 value of 20 nM.
Xu
G
G
Department of Medicinal Chemistry and Molecular Pharmacology, School of Pharmacy and Pharmacal Sciences, Purdue University, West Lafayette, Indiana 47907, USA.
Loftus
T L
TL
Wargo
H
H
Turpin
J A
JA
Buckheit
R W
RW
Cushman
M
M
D019380:Anti-HIV Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D002208:Caproates / Q000138:chemical synthesis / Q000494:pharmacology; D002460:Cell Line; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors*; D015497:HIV-1 / Q000187:drug effects; D006801:Humans; D018894:Reverse Transcriptase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D013237:Stereoisomerism
D019380:Anti-HIV Agents; D002208:Caproates; D018894:Reverse Transcriptase Inhibitors; D054303:HIV Reverse Transcriptase