Aminopyrimidinimino isatin analogues: design and synthesis of novel non- nucleoside HIV-1 reverse transcriptase inhibitors with broad-spectrum anti-microbial properties.
HIV is the most significant risk factor for many opportunistic infections like tuberculosis, 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'-chloroben-zylpyrimidin-2'-yl)imino-1'-(5-methylisatinyl)] methyl]N(1)-piperazinyl]-3-quinoline carboxylic acid (10) emerged as the most potent broad-spectrum chemotherapeutic agent active against HIV-1 replication (EC(50): 9.4 microg /ml), M. tuberculosis (MIC: 3.13 microg /ml) and various pathogenic bacteria (MIC's: 1.22 microg /ml).
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
D000890:Anti-Infective Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D001419:Bacteria / Q000187:drug effects; D002478:Cells, Cultured; D015195:Drug Design; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors*; D015497:HIV-1 / Q000187:drug effects / Q000201:enzymology; D006801:Humans; D007097:Imines / Q000737:chemistry; D007211:Indoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D007510:Isatin / Q000737:chemistry; D007854:Lead / Q000737:chemistry; D009169:Mycobacterium tuberculosis / Q000187:drug effects; D011743:Pyrimidines / Q000737:chemistry; D011804:Quinolines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D018894:Reverse Transcriptase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D014779:Virus Replication / Q000187:drug effects
C512756:1-ethyl-6-fluoro-1,4-dihydro-4-oxo-7-((N4-(3'-(4'-amino-5'-chlorobenzylpyrimidin-2'-yl)imino-1'-(5-methylisatinyl))methyl)-N1-piperazinyl)-3-quinolinecarboxylic acid; D000890:Anti-Infective Agents; D007097:Imines; D007211:Indoles; D011743:Pyrimidines; D011804:Quinolines; D018894:Reverse Transcriptase Inhibitors; D007854:Lead; D007510:Isatin; D054303:HIV Reverse Transcriptase