:: Volume 2, Issue 3 And 4 (7-1998) ::
IBJ 1998, 2(3 And 4): 105-113 Back to browse issues page
Evaluation of (5R,6R)-5-Bromo-6-Ethoxy-5-Ethyl-5,6-Dihydro-2'- Deoxyuridine as a Brain-Targeted Prodrug of 5-Ethyl-2'- Deoxyuridine
Majid Cheraghali , Rakesh Kumar , Kevin W. Morin , Edward E. Knaus , Leonard I. Wiebe
Abstract:  
(+)-Trans-(5R,6R)-5-bromo-6-ethoxy-5-ethyl-5,6-dihydro-2'-deoxyuridine [(5R,6R)-BEEDU], a po‌tential brain-targeted prodrug of 5-ethyl-2'-deoxyuridine (EDU), was synthesized by the regiospecific addition of BrOEt to the 5,6-olefinic bond of EDU. (5R,6R)-BEEDU is more lipophilic (log P = 0.04) than EDU (log P = -1.09). In vitro incubation of (5R,6R)-BEEDU with rat whole blood and brain ho‌mogenate resulted in a 53% and 16% conversion, respectively, to EDU. In contrast, (5R,6R)-BEEDU was not converted to EDU upon incubation with glutathione (GSH) at 37°C for 36 hours. After i.v. injection into rats, (5R,6R)-BEEDU was rapidly converted to EDU, which was then further metabo‌lized like EDU. However, (5R,6R)-BEEDU provided a substantially higher Ryncentration of EDU in blood, relative to that when EDU was injected. A biodistribution study of [4- C]-(5R,6R)-BEEDU in Balb/c mice showed that (5R,6R)-BEEDU provided significantly higher (P < 0.05) radirctivityievels in brain samples at 8, 18 and 30 min post injection than observfid after injection of [4- C]-EDU. The higher repioactivity levels in liver samples after injection of [4- C]-(5R,6R)-BEEDU, relative to those after [4- C]-EDU, indicates that the 5,6-dihydro derivative undergoes a higher hepatic extraition than EDU. Clearance of radioactivity from blood qv' excretion into urine, after injection of [4 C]‌EDU, was much faster than that after injection of [4- C]-(5R,6R)-BEEDU.
Keywords: 5-Ethyl-2-deoxyuridine, Dihydro prodrugs, Herpes Simplex Virus, Brain-targeted
Full-Text [PDF 444 kb]      
Type of Study: Full Length |
Add your comments about this article
Your username or Email:

CAPTCHA code


XML     Print


Download citation:
BibTeX | RIS | EndNote | Medlars | ProCite | Reference Manager | RefWorks
Send citation to:

Cheraghali M, Kumar R, Morin K W, Knaus E E, Wiebe L I. Evaluation of (5R,6R)-5-Bromo-6-Ethoxy-5-Ethyl-5,6-Dihydro-2'- Deoxyuridine as a Brain-Targeted Prodrug of 5-Ethyl-2'- Deoxyuridine. IBJ. 1998; 2 (3 and 4) :105-113
URL: http://ibj.pasteur.ac.ir/article-1-862-en.html


Volume 2, Issue 3 And 4 (7-1998) Back to browse issues page
Persian site map - English site map - Created in 0.17 seconds with 37 queries by YEKTAWEB 3781