5H-pyrrolo[1,2-b][1,2,5]benzothiadiazepines (PBTDs): A novel class of non-nucleoside reverse transcriptase inhibitors
| Autor: | Maria Grazia Spiga, Anna Giulia Loi, Romano Silvestri, Silvio Massa, M. Putzolu, Simona Corrias, Paolo La Colla, E. Pagnozzi, Marino Artico, Giorgio Stefancich |
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| Přispěvatelé: | M., Artico, R., Silvestri, E., Pagnozzi, Stefancich, Giorgio, S., Massa, A. G., Loi, M., Putzolu, S., Corria, M. G., Spiga, P., LA COLLA |
| Rok vydání: | 1996 |
| Předmět: |
Magnetic Resonance Spectroscopy
Spectrophotometry Infrared Anti-HIV Agents Thiazepines Stereochemistry Clinical Biochemistry Pharmaceutical Science Virus Replication Biochemistry Pyrrolidine Cell Line Nucleoside Reverse Transcriptase Inhibitor law.invention Structure-Activity Relationship chemistry.chemical_compound law Drug Discovery Humans Structure–activity relationship Potency Molecular Biology Pyrrole Chemistry Organic Chemistry HIV Reverse Transcriptase In vitro Reverse transcriptase HIV-1 Recombinant DNA Reverse Transcriptase Inhibitors Molecular Medicine |
| Zdroj: | Bioorganic & Medicinal Chemistry. 4:837-850 |
| ISSN: | 0968-0896 |
| Popis: | 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). |
| Databáze: | OpenAIRE |
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