title: 1,5-Benzodiazepines. Part XII. Synthesis and biological evaluation of tricyclic and tetracyclic 1,5-benzodiazepine derivatives as nevirapine analogues.
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.
authors.affiliation: Dipartimento di Scienze Farmaceutiche, Università di Genova, Viale Benedetto XV, 3, I-16132 Genoa, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Di Braccio
authors.forename: G
authors.initials: G
authors.lastname: Grossi
authors.forename: G
authors.initials: G
authors.lastname: Roma
authors.forename: L
authors.initials: L
authors.lastname: Vargiu
authors.forename: M
authors.initials: M
authors.lastname: Mura
authors.forename: M E
authors.initials: ME
authors.lastname: Marongiu
mesh_terms: D001569:Benzodiazepines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002460:Cell Line; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D008826:Microbial Sensitivity Tests; D019829:Nevirapine / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors; D018894:Reverse Transcriptase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013601:T-Lymphocytes / Q000187:drug effects*
chemical_list: D011994:Recombinant Proteins; D018894:Reverse Transcriptase Inhibitors; D001569:Benzodiazepines; D019829:Nevirapine; D054303:HIV Reverse Transcriptase