title: 5H-pyrrolo[1,2-b] [1,2,5]benzothiadiazepines (PBTDs): a novel class of non-nucleoside reverse transcriptase inhibitors.
abstract: With the aim of developing novel inhibitors of human immunodeficiency virus, various derivatives (10-17) related to 5H-pyrrolo[1,2-b] [1,2,5]benzothiadiazepine (PBTD) were prepared and tested in vitro. The title tricyclic derivatives were obtained by intramolecular cyclization of the open-chain intermediate arylpyrrylsulfones, followed by N-alkylation at position 10. Among test derivatives some 10-alkyl-5H-pyrrolo[1,2-b] [1,2,5]benzothiadiazepin-11(10H)-one-5,5-dioxides were found to exert potent and specific activity against HIV-1. In particular, 7-chloro derivatives 11i and j showed a potency comparable to that of nevirapine. However, when the chloro atom was shifted to the 8 position, the related products were scarcely active or totally inactive. Replacement of the pyrrole with pyrrolidine led to inactive products and the reduction of SO2 to S strongly diminished the antiviral potency. PBTD derivatives active in cell cultures were also inhibitory to the recombinant HIV-1 RT in enzyme assays, thus allowing the conclusion that PBTDs are a new class of non-nucleoside reverse transcriptase inhibitors (NNRTIs).
authors.affiliation: Dipartimento di Studi Farmaceutici, Università di Roma La Sapienza, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Artico
authors.forename: R
authors.initials: R
authors.lastname: Silvestri
authors.forename: E
authors.initials: E
authors.lastname: Pagnozzi
authors.forename: G
authors.initials: G
authors.lastname: Stefancich
authors.forename: S
authors.initials: S
authors.lastname: Massa
authors.forename: A G
authors.initials: AG
authors.lastname: Loi
authors.forename: M
authors.initials: M
authors.lastname: Putzolu
authors.forename: S
authors.initials: S
authors.lastname: Corrias
authors.forename: M G
authors.initials: MG
authors.lastname: Spiga
authors.forename: P
authors.initials: P
authors.lastname: La Colla
mesh_terms: D019380:Anti-HIV Agents / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D054303:HIV Reverse Transcriptase / Q000187:drug effects*; D015497:HIV-1 / Q000187:drug effects / Q000201:enzymology*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D018894:Reverse Transcriptase Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D013055:Spectrophotometry, Infrared; D013329:Structure-Activity Relationship; D013841:Thiazepines / Q000737:chemistry / Q000494:pharmacology*; D014779:Virus Replication / Q000187:drug effects
chemical_list: D019380:Anti-HIV Agents; D018894:Reverse Transcriptase Inhibitors; D013841:Thiazepines; D054303:HIV Reverse Transcriptase