Studies designed to increase the stability and antiviral activity (HCMV) of the active benzimidazole nucleoside, TCRB.
The potent activity of 2,5,6-trichloro-1-(beta-D-ribofuranosyl)benzimidazole (TCRB) against Human Cytomegalovirus with the concomitant low cellular toxicity at concentrations that inhibit viral growth prompted considerable interest in this research area. This interest was moderated by the pharmacokinetic studies of TCRB in rats and monkeys that revealed the instability of TCRB in vivo. These studies suggested that the instability was due to a cleavage of the glycosidic bond in vivo which released the heterocycle (2,5,6-trichlorobenzimidazole) into the bloodstream. This prompted us to initiate synthetic studies designed to increase the stability of the glycosidic bond of TCRB and BDCRB. Several synthetic approaches to address this and other problems are presented.
Townsend
L B
LB
University of Michigan, Department of Medicinal Chemistry, College of Pharmacy, Ann Arbor 48109, USA.
Gudmundsson
K S
KS
Daluge
S M
SM
Chen
J J
JJ
Zhu
Z
Z
Koszalka
G W
GW
Boyd
L
L
Chamberlain
S D
SD
Freeman
G A
GA
Biron
K K
KK
Drach
J C
JC
D000818:Animals; D000998:Antiviral Agents / Q000737:chemistry* / Q000494:pharmacology*; D001562:Benzimidazoles / Q000737:chemistry* / Q000494:pharmacology*; D003587:Cytomegalovirus / Q000187:drug effects*; D000882:Haplorhini; D008826:Microbial Sensitivity Tests; D051381:Rats; D012263:Ribonucleosides / Q000737:chemistry* / Q000494:pharmacology*
C111642:2,5,6-trichloro-1-(ribofuranosyl)benzimidazole; D000998:Antiviral Agents; D001562:Benzimidazoles; D012263:Ribonucleosides