Synthesis of a non-nucleoside reverse transcriptase inhibitor in the alkenyldiarylmethane (ADAM) series with optimized potency and therapeutic index

M Cushman, A Casimiro-Garcia, K Williamson…

Index: Cushman, Mark; Casimiro-Garcia, Agustin; Williamson, Karen; Rice, William G. Bioorganic and Medicinal Chemistry Letters, 1998 , vol. 8, # 2 p. 195 - 198

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Citation Number: 23

Abstract

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 μM, providing a therapeutic index of 2430. ADAM II is a non-nucleoside reverse transcriptase inhibitor, displaying an IC50 of 0.3 μM with poly (rC) oligo (dG) as the template/primer.