Pyrrolobenzoxazepinones (PBOs) represent a new class of human immunodeficiency virus type 1 (HIV-1) nonnucleoside reverse transcriptase (RT) inhibitors (NNRTIs) whose prototype is 5. Molecular modeling studies based on the X-ray structures of HIV-1 RT prompted the synthesis of novel analogues which were tested as anti-HIV agents. The PBO derivatives specifically designed to target the highly conserved amino acid residues within the â12-â13 hairpin, namely primer grip, proved to be very potent against the most common mutant enzymes, including the highly resistant K103N mutant strain. Structure-activity relationships (SARs) are discussed in terms of a possible interaction with the RT binding site, depending on the nature of the substituents at C-6. Among the pyrrolobenzoxazepines investigated, 15c appeared to be the most promising NNRTI of the series characterized by potent antiviral activity, broad spectrum, and low cytotoxicity. 15c showed synergistic antiviral activity with AZT.

Fattorusso, C., Gemma, C., Butini, S., Huleatt, P., Catalanotti, B., Persico, M., et al. (2005). Specific Targeting Highly Conserved Residues in the HIV-1 Reverse Transcriptase Primer Grip Region. Design, Synthesis, and Biological Evaluation of Novel, Potent, and Broad Spectrum NNRTIs with Antiviral Activity. JOURNAL OF MEDICINAL CHEMISTRY, 48(23), 7153-7165.

Specific Targeting Highly Conserved Residues in the HIV-1 Reverse Transcriptase Primer Grip Region. Design, Synthesis, and Biological Evaluation of Novel, Potent, and Broad Spectrum NNRTIs with Antiviral Activity

BERGAMINI, ALBERTO;MARINI, STEFANO;COLETTA, MASSIMILIANO;
2005-11-01

Abstract

Pyrrolobenzoxazepinones (PBOs) represent a new class of human immunodeficiency virus type 1 (HIV-1) nonnucleoside reverse transcriptase (RT) inhibitors (NNRTIs) whose prototype is 5. Molecular modeling studies based on the X-ray structures of HIV-1 RT prompted the synthesis of novel analogues which were tested as anti-HIV agents. The PBO derivatives specifically designed to target the highly conserved amino acid residues within the â12-â13 hairpin, namely primer grip, proved to be very potent against the most common mutant enzymes, including the highly resistant K103N mutant strain. Structure-activity relationships (SARs) are discussed in terms of a possible interaction with the RT binding site, depending on the nature of the substituents at C-6. Among the pyrrolobenzoxazepines investigated, 15c appeared to be the most promising NNRTI of the series characterized by potent antiviral activity, broad spectrum, and low cytotoxicity. 15c showed synergistic antiviral activity with AZT.
nov-2005
Pubblicato
Rilevanza internazionale
Articolo
Esperti anonimi
Settore BIO/10 - BIOCHIMICA
English
Con Impact Factor ISI
HIV, antivirals
Fattorusso, C., Gemma, C., Butini, S., Huleatt, P., Catalanotti, B., Persico, M., et al. (2005). Specific Targeting Highly Conserved Residues in the HIV-1 Reverse Transcriptase Primer Grip Region. Design, Synthesis, and Biological Evaluation of Novel, Potent, and Broad Spectrum NNRTIs with Antiviral Activity. JOURNAL OF MEDICINAL CHEMISTRY, 48(23), 7153-7165.
Fattorusso, C; Gemma, C; Butini, S; Huleatt, P; Catalanotti, B; Persico, M; De Angelis, M; Fiorini, I; Nacci, V; Ramunno, A; Rodriquez, M; Greco, G; N...espandi
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/67359
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