title: in vitro inhibition of the measles virus by novel ring-expanded ('fat') nucleoside analogues containing the imidazo[4,5-e]diazepine ring system.
abstract: The synthesis and in vitro anti-measles virus (anti-MV) activity of a class of ring-expanded ('fat') nucleoside analogues (1-4) containing the title heterocyclic ring system are reported. The target compounds were synthesized by base-catalyzed condensations of 4,5-dicarboxylic acid esters of the appropriately substituted imidazole-1-ribosides with suitably substituted guanidine derivatives. Compounds were screened for anti-MV activity in African green monkey kidney cells (CV-1), employing ribavirin as the control standard. While the parent compound 1 itself failed to show any significant antiviral activity against MV, its analogues containing hydrophobic substituents at the 2-position (2) or the 6-position (4) showed promising antiviral activity at submicromolar or micromolar concentration levels with no apparent toxicity to the host cell line. Both compounds showed higher anti-MV activity than the control drug ribavirin.
authors.affiliation: Laboratory for Drug Design and Synthesis, Department of Chemistry and Biochemistry, University of Maryland, Baltimore County 21250, USA.
authors.forename: Ning
authors.initials: N
authors.lastname: Zhang
authors.forename: Huan-Ming
authors.initials: HM
authors.lastname: Chen
authors.forename: Ramesh
authors.initials: R
authors.lastname: Sood
authors.forename: Kishna
authors.initials: K
authors.lastname: Kalicharran
authors.forename: Ali I
authors.initials: AI
authors.lastname: Fattom
authors.forename: Robert B
authors.initials: RB
authors.lastname: Naso
authors.forename: Dale L
authors.initials: DL
authors.lastname: Barnard
authors.forename: Robert W
authors.initials: RW
authors.lastname: Sidwell
authors.forename: Ramachandra S
authors.initials: RS
authors.lastname: Hosmane
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000737:chemistry* / Q000494:pharmacology*; D001381:Azepines / Q000737:chemistry / Q000494:pharmacology; D002460:Cell Line; D002522:Chlorocebus aethiops; D019791:Guanidine / Q000737:chemistry; D057927:Hydrophobic and Hydrophilic Interactions; D007093:Imidazoles / Q000737:chemistry / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D007668:Kidney / Q000166:cytology; D008459:Measles virus / Q000187:drug effects*; D009705:Nucleosides / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D000998:Antiviral Agents; D001381:Azepines; D007093:Imidazoles; D009705:Nucleosides; D019791:Guanidine