title: Acyclic nucleoside/nucleotide analogues with an imidazole ring skeleton.
abstract: Syntheses of a few acyclic nucleoside and acyclic nucleoside phosphonate analogues containing an imidazole ring have been reported. These analogues include methyl 1-(2-hydroxyethoxymethyl)imidazole-4, 5-dicarbo-xylate (1), 4,5-dicarbamoyl-1-(2-hydroxyethoxymethyl)imidazole (2), 4,5-dicyano-1-(2-hydroxyethoxymethyl)imidazole (4), Methyl 1-(2-bromoethoxymethyl)imidazole-4,5-dicarboxylate (7), 4,5-dicyano-(2-bromoethoxymethyl)imidazole (8), and Methyl 1-(2-phosphonomethoxyethyl)imidazole (10). Also reported are a few potential prodrugs of the above compounds, including the acetyl derivatives 5 and 6 (of 1 and 4, respectively), and the diethyl phosphonate ester 9 (of 10). In addition, the corresponding benzyl-protected precursors 11 and 12 (of 1 and 4, respectively), along with their common hydrolysis product, 1-(2-benzyloxy-ethoxymethyl)-4,5-imidazoledicarboxylic acid (3), are reported. Another potential prodrug included in the list is 1-(2-acetoxyethyl)-4,5-dicyanoimidazole (15). The compounds were screened for in vitro antiviral activity against a wide variety of herpes and respiratory viruses. The most active compound was the phosphonate analogue 9 which exhibited an anti-measles virus activity with an EC50 of <2.5 microg/mL and an SI value of > 176.
authors.affiliation: Department of Chemistry & Biochemistry, University of Maryland, Baltimore County, Baltimore 21250, USA.
authors.forename: H M
authors.initials: HM
authors.lastname: Chen
authors.forename: R S
authors.initials: RS
authors.lastname: Hosmane
mesh_terms: D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002855:Chromatography, Thin Layer; D003588:Cytopathogenic Effect, Viral / Q000187:drug effects; D015195:Drug Design; D007093:Imidazoles / Q000138:chemical synthesis / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D009499:Neutral Red / Q000378:metabolism; D009705:Nucleosides / Q000138:chemical synthesis* / Q000737:chemistry; D009711:Nucleotides / Q000138:chemical synthesis* / Q000737:chemistry; D013329:Structure-Activity Relationship; D014780:Viruses / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D007093:Imidazoles; D009705:Nucleosides; D009711:Nucleotides; D009499:Neutral Red; C029899:imidazole