Title: Structural features and anti-HIV activity of the isomers of 1-(2’,6’-difluorophenyl)-1H,3H-thiazolo[3,4-a]benzimidazole, a potent non-nucleoside HIV-1 reverse transcriptase inhibitor
Authors: Chimirri, A ×
Grasso, S
Molica, C
Monforte, A-M
Monforte, P
Zappala, M
Bruno, G
Nicolo, F
Witvrouw, Myriam
Jonckheere, H
Balzarini, Jan
De Clercq, Erik #
Issue Date: 1997
Series Title: Antivir Chem Chemoth vol:8 pages:363-370
Abstract: The structural features, including the absolute configuration, of the enantiomers of 1-(2',6'-difluorophenyl)-1H,3H-thiazolo[3,4-a]benzimidazole (TBZ; NSC 625487), the lead compound of a new class of human immunodeficiency virus type 1 (HIV-1) non-nucleoside reverse transcriptase inhibitors (NNRTIs), are described. Diffractometric analysis revealed that TBZ, like other NNRTIs, assumes a butterfly-like conformation in which the phenyl ring at C1 is in an orthogonal orientation relative to the thiazolobenzimidazole system, and the 2',6'-fluorine atoms form two intramolecular hydrogen bonds with H1 and one of the methylene protons at C3, respectively. The stereochemistry in solution, as confirmed by lanthanide shift reagent-assisted H-1 NMR, paralleled the situation present in the solid state. The in the vitro anti-HIV activity of the two enantiomers was also evaluated and the results obtained showed that the R-(+) is more active than the S-(-) isomer in inhibiting HIV-1 replication. Resistance and cross-resistance to other NNRTIs as well as inhibitory effects on HIV-1 reverse transcriptase activity are also reported.
ISSN: 0956-3202
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory of Virology and Chemotherapy (Rega Institute)
Molecular Virology and Gene Therapy
× corresponding author
# (joint) last author

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