Synthesis and HIV-1 Reverse Transcriptase Inhibitory Activity of Non-Nucleoside Phthalimide Derivatives

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-dihydroxybenzyl)phthalimide (11), N-[2-(α-furyl)ethyl]phthalimide (29) and N-(5-methylpyrazin-2-ylmethyl)phthalimide (25) exhibited IC₅₀ values of 60.90, 98.10 and 120.75 µg/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).