Studies Designed to Increase the Stability and Antiviral Activity (HCMV) of the Active Benzimidazole Nucleoside,TCRB |
| |
| Authors: | Leroy B Townsend Kristjan S Gudmundsson Susan M Daluge Jiong J Chen Zhijian Zhu George W Koszalka |
| |
| Institution: | 1. Department of Medicinal Chemistry, Department of Chemistry , College of Pharmacy, College of Literature, Science, and the Arts, University of Michigan , Ann Arbor, Michigan, 48109, USA;2. Biologic and Materials Sciences Department , School of Dentistry , Ann Arbor, Michigan, 48109, USA;3. Glaxo Wellcome Co. , Five Moore Drive, Research Triangle Park, North Carolina, 27709, USA |
| |
| Abstract: | Abstract The potent activity of 2,5,6-trichloro-1-(ß-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. |
| |
| Keywords: | |
|
|
