Design, synthesis and biological evaluation of novel non-nucleoside HIV-1 reverse transcriptase inhibitors with broad-spectrum chemotherapeutic properties.
Acquired immunodeficiency syndrome (AIDS) results from infection by the retrovirus, human immunodeficiency virus (HIV). HIV is the most significant risk factor for many opportunistic infections like tuberculosis, hepatitis, bacterial infections, etc. In this paper, we designed aminopyrimidinimino isatin lead compound as a novel non-nucleoside reverse transcriptase inhibitor with broad-spectrum chemotherapeutic properties for the effective treatment of AIDS and AIDS-related opportunistic infections. Compound 1-ethyl-6-fluoro-1,4-dihydro-4-oxo-7[[N(4)-[3'-(4'-amino-5'-trimethoxybenzylpyrimidin-2'-yl)imino-1'-(5-fluoroisatinyl)]methyl]-N(1)-piperazinyl]-3-quinoline carboxylic acid (12) emerged as the most potent broad-spectrum chemotherapeutic agent active against HIV, HCV, Mycobacterium tuberculosis and various pathogenic bacteria.
Sriram
Dharmarajan
D
Medicinal Chemistry Research Laboratory, Pharmacy Group, Birla Institute of Technology and Science, Pilani 333031, India. dsriram@bits-pilani.ac.in
Bal
Tanushree Ratan
TR
Yogeeswari
Perumal
P
D000818:Animals; D019380:Anti-HIV Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D002460:Cell Line; D015195:Drug Design; D004353:Drug Evaluation, Preclinical / Q000379:methods; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015497:HIV-1 / Q000187:drug effects* / Q000201:enzymology* / Q000254:growth & development; D006801:Humans; D008297:Male; D051379:Mice; D018894:Reverse Transcriptase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology
D019380:Anti-HIV Agents; D000970:Antineoplastic Agents; D018894:Reverse Transcriptase Inhibitors; D054303:HIV Reverse Transcriptase