in vitro inhibition of the measles virus by novel ring-expanded ('fat') nucleoside analogues containing the imidazo[4,5-e]diazepine ring system.
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.
Zhang
Ning
N
Laboratory for Drug Design and Synthesis, Department of Chemistry and Biochemistry, University of Maryland, Baltimore County 21250, USA.
Chen
Huan-Ming
HM
Sood
Ramesh
R
Kalicharran
Kishna
K
Fattom
Ali I
AI
Naso
Robert B
RB
Barnard
Dale L
DL
Sidwell
Robert W
RW
Hosmane
Ramachandra S
RS
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*
D000998:Antiviral Agents; D001381:Azepines; D007093:Imidazoles; D009705:Nucleosides; D019791:Guanidine