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Updated: Jul 18, 2026

Quantitative Structure-Activity Relationship, Activity Prediction, and Molecular Dynamics of Non-nucleotide Reverse Transcriptase Inhibitors
Published on: May 9, 2025
Synthesis and anti-HIV activity of nevirapine prodrugs
D Sriram1, P Yogeeswari, M R K Kishore
1Medicinal Chemistry Research Laboratory, Pharmacy Group, Birla Institute of Technology and Science, Pilani - 333031 (Rajasthan), India. dsriram@bits-pilani.ac.in
Abstract:
The synthesis, in vitro anti-HIV activity and stability studies of the N-Mannich bases of nevirapine are reported. Among the synthesized compounds, 5-{[4-(4-chlorophenyl)piperazin-1 -yl]methyl}-1-cyclopropyl-4-methyl-5,11-dihydro-6H-dipyrido[2,3-e:3',2'-b][1,4]diazepin-6-one (3) was found to be the most potent compound with EC50 of 0.0159 microM against HIV-1 replication and CC50 of >1000 microM against CEM cell lines with selectivity index of >62893. Compound 3 was five times more active than nevirapine (EC50 of 0.09 microM). In vitro hydrolysis of the Mannich bases in phosphate buffer (pH 7.4) indicated that these agents were relatively stable with t1/2 ranging from 15 to 240 min.
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