1. 1,5-Benzodiazepines. Part XII. Synthesis and biological evaluation of tricyclic and tetracyclic 1,5-benzodiazepines derivatives as nevirapine analogues
- Author
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Maria Elena Marongiu, Laura Vargiu, Mario Di Braccio, Giorgio Roma, Giancarlo Grossi, and Massimo Mura
- Subjects
Nevirapine ,medicine.drug_class ,Stereochemistry ,T-Lymphocytes ,Microbial Sensitivity Tests ,Chemical synthesis ,Cell Line ,chemistry.chemical_compound ,Benzodiazepines ,Drug Discovery ,medicine ,Humans ,Pharmacology ,chemistry.chemical_classification ,Benzodiazepine ,Reverse-transcriptase inhibitor ,biology ,Organic Chemistry ,General Medicine ,HIV Reverse Transcriptase ,Recombinant Proteins ,Enzyme ,chemistry ,Enzyme inhibitor ,biology.protein ,Lactam ,HIV-1 ,Reverse Transcriptase Inhibitors ,Tricyclic ,medicine.drug - Abstract
A number of properly substituted 5H-pyrimido[4,5-b][1,5]benzodiazepines (2) and pyrazolo[3,4-b][1,5]benzodiazepines (3 and 4), as well as compounds 5-7, which are derivatives of new tetracyclic systems, were prepared as nevirapine analogues through multistep synthetic routes. The cytotoxic and anti-HIV-1 properties of compounds 2-7 were evaluated in cell-based assays, together with their inhibitory activity against the HIV-1 recombinant reverse transcriptase (rRT) in enzyme assays. The modifications introduced into nevirapine heterocyclic skeleton proved to have a negative effect for the anti-HIV-1 activity. It is worth noting that some of the new derivatives proved to be cytotoxic in the low micromolar range.
- Published
- 2001