title: Synthesis and anti-HIV activity of nevirapine prodrugs.
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.
authors.affiliation: Medicinal Chemistry Research Laboratory, Pharmacy Group, Birla Institute of Technology and Science, Pilani - 333031 (Rajasthan), India. dsriram@bits-pilani.ac.in
authors.forename: D
authors.initials: D
authors.lastname: Sriram
authors.forename: P
authors.initials: P
authors.lastname: Yogeeswari
authors.forename: M R K
authors.initials: MR
authors.lastname: Kishore
mesh_terms: D019380:Anti-HIV Agents / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000821:virology; D002460:Cell Line; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D004355:Drug Stability; D006801:Humans; D006868:Hydrolysis; D007202:Indicators and Reagents; D019829:Nevirapine / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D011355:Prodrugs / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology
chemical_list: D019380:Anti-HIV Agents; D007202:Indicators and Reagents; D011355:Prodrugs; D019829:Nevirapine