Synthesis and HIV-1 reverse transcriptase inhibitory activity of non-nucleoside phthalimide derivatives

Abstract

A new type of non-nucleoside HIV-1 reverse transcriptase inhibitors in phthalimide series has been synthesized from either the reaction of N-carboethoxyphthalimide with amines or phthalimide with appropriate alkyl halides. The in vitro inhibitory activity of the synthesized compounds was studied by a radiometric assay at a concentration of 200 μg/mL using poly(rA)·oligo(dT) as a template-primer and methyl-[3H]dTTP as a substrate. The three most potent compounds, N-(m,p-dihydroxybenayl) phihalimide (11), N-[2-(a-furyl)ethyl]phthalimide (29) and N-(5-methylpyrazin-2- ylmethyl)phthalimide (25) exhibited IC50 values of 60.90, 98.10 and 120.75 μ/mL, respectively, lower than IC50 of delavirdine (502.22 μg/mL, using poly(rA)·oligo(dT) as a template-primer and [ 3H]dTTP as a substrate). © 2008 SIOC, CAS, & Wiley-VCH Verlag GmbH & Co. KGaA.