title: Synthesis and biological activity of novel 1H,3H-thiazolo[3,4-a]benzimidazoles: non-nucleoside human immunodeficiency virus type 1 reverse transcriptase inhibitors.
abstract: Using a known human immunodeficiency virus type 1 (HIV-1) non-nucleoside reverse transcriptase inhibitor (NNRTI), 1-(2,6-difluorophenyl)-1H,3H-thiazolo[3,4-a]benzimidazole (TBZ NSC 625487) as the lead structure for drug design, a series of novel 1H,3H-thiazolo[3,4-a]benzimidazole derivatives substituted on the benzene-fused ring was prepared. Their in vitro anti-HIV-1 activity, as well as their inhibitory effects on the viral reverse transcriptase, were evaluated. The structure-activity relationships for these compounds are described and the results suggest that the apolar binding pocket of RT, into which the NNRTIs must fit, can accommodate only groups with a limited size and shape.
authors.affiliation: Dipartimento Farmaco-Chimico, Università di Messina, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Chimirri
authors.forename: S
authors.initials: S
authors.lastname: Grasso
authors.forename: P
authors.initials: P
authors.lastname: Monforte
authors.forename: A
authors.initials: A
authors.lastname: Rao
authors.forename: M
authors.initials: M
authors.lastname: Zappalà
authors.forename: A M
authors.initials: AM
authors.lastname: Monforte
authors.forename: C
authors.initials: C
authors.lastname: Pannecouque
authors.forename: M
authors.initials: M
authors.lastname: Witvrouw
authors.forename: J
authors.initials: J
authors.lastname: Balzarini
authors.forename: E
authors.initials: E
authors.lastname: De Clercq
mesh_terms: D019380:Anti-HIV Agents / Q000138:chemical synthesis / Q000494:pharmacology; D001562:Benzimidazoles / Q000138:chemical synthesis* / Q000494:pharmacology*; D002460:Cell Line; D015497:HIV-1 / Q000187:drug effects; D015498:HIV-2 / Q000187:drug effects; D006801:Humans; D015394:Molecular Structure; D018894:Reverse Transcriptase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D019380:Anti-HIV Agents; D001562:Benzimidazoles; D018894:Reverse Transcriptase Inhibitors