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

AbstractA 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).