Solid-Phase Synthesis of the Alkenyldiarylmethane (ADAM) Series of Non-Nucleoside HIV-1 Reverse Transcriptase Inhibitors

• Published in: Journal of organic chemistry Vol. 66; no. 18; pp. 5958 - 5964
• Main Authors: Xu, Guozhang, Loftus, Tracy L, Wargo, Heather, Turpin, Jim A, Buckheit, Robert W, Cushman, Mark
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 07.09.2001; Amer Chemical Soc
• Subjects: Anti-HIV Agents - chemical synthesis; Anti-HIV Agents - pharmacology; Caproates - chemical synthesis; Caproates - pharmacology; Cell Line; Chemistry; Chemistry, Organic; HIV Reverse Transcriptase - antagonists & inhibitors; HIV-1 - drug effects; Humans; Physical Sciences; Reverse Transcriptase Inhibitors - chemical synthesis; Reverse Transcriptase Inhibitors - pharmacology; Science & Technology; Stereoisomerism; VIRUS TYPE-1 HIV-1; SELECTIVE-INHIBITION; LIBRARIES; COUPLING REACTIONS; DRUG DISCOVERY; BIOLOGICAL EVALUATION; STILLE; ANTIRETROVIRAL THERAPY; AGENTS; DERIVATIVES
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/jo0100291

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.