Synthesis of a non-nucleoside reverse transcriptase inhibitor in the alkenyldiarylmethane (ADAM) series with optimized potency and therapeutic index.
A novel alkenyldiarylmethane (ADAM) analog has been synthesized with enhanced potency as an anti-HIV agent. The new compound (ADAM II) inhibits the cytopathic effect of HIV-1RF in CEM-SS cells with an EC50 of 13 nM, while it shows cytotoxicity with a CC50 of 31.6 microM, providing a therapeutic index of 2430. ADAM II is a non-nucleoside reverse transcriptase inhibitor, displaying an IC50 of 0.3 microM with poly(rC) oligo(dG) as the template/primer.
Cushman
M
M
Department of Medicinal Chemistry and Molecular Pharmacology, School of Pharmacy and Pharmacal Sciences, Purdue University, West Lafayette, Indiana 47907, USA.
Casimiro-Garcia
A
A
Williamson
K
K
Rice
W G
WG
D019380:Anti-HIV Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002460:Cell Line; D003588:Cytopathogenic Effect, Viral / Q000187:drug effects; D015497:HIV-1 / Q000187:drug effects / Q000472:pathogenicity; D006801:Humans; D008958:Models, Molecular; D018894:Reverse Transcriptase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
D019380:Anti-HIV Agents; D018894:Reverse Transcriptase Inhibitors