title: Synthesis, structure and in vitro anti-human immunodeficiency virus activity of novel 3-methyl-1H,3H-thiazolo[3,4-a]benzimidazoles.
abstract: A series of novel 1-aryl-3-methyl-1H,3H-thiazolo[3,4-a]benzimidazoles, TBZ analogues, were synthesized and investigated as anti-human immunodeficiency virus (HIV) agents in order to study the effects of structural modifications on antiviral activity and cytotoxicity. They were proved to inhibit significantly HIV-1 replication in vitro without showing inhibitory activity on HIV-2 or simian immunodeficiency virus. Their potency was influenced by the presence of suitable substituents in the phenyl ring at C-1 as well as by their stereochemical characteristics. In fact, the most active compound of the series was the trans-1-(2,6-difluorophenyl)-3-methyl-1H,3H-thiazolo[3,4- a]benzimidazole, in which the butterfly-like conformation is stabilized by two intramolecular hydrogen bonds between the fluorine atoms and H-1 and H-3. This was made possible by the trans arrangement of C-1 and C-3 substituents, as shown by X-ray and NMR analysis.
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: A M
authors.initials: AM
authors.lastname: Monforte
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: G
authors.initials: G
authors.lastname: Bruno
authors.forename: F
authors.initials: F
authors.lastname: Nicolò
authors.forename: C
authors.initials: C
authors.lastname: Pannecouque
authors.forename: M
authors.initials: M
authors.lastname: Witvrouw
authors.forename: E
authors.initials: E
authors.lastname: De Clercq
mesh_terms: D019380:Anti-HIV Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D000998:Antiviral Agents / Q000138:chemical synthesis / Q000494:pharmacology; D001562:Benzimidazoles / Q000138:chemical synthesis* / Q000494:pharmacology; D002460:Cell Line; D018360:Crystallography, X-Ray; D017611:Fluorine Compounds / Q000138:chemical synthesis / Q000494:pharmacology; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008968:Molecular Conformation; D015394:Molecular Structure; D013844:Thiazoles / Q000138:chemical synthesis* / Q000494:pharmacology; D014779:Virus Replication / Q000187:drug effects
chemical_list: D019380:Anti-HIV Agents; D000998:Antiviral Agents; D001562:Benzimidazoles; D017611:Fluorine Compounds; D013844:Thiazoles