en مقاله کامل Full Length/Original Article (+)-Trans-(5R,6R)-5-bromo-6-ethoxy-5-ethyl-5,6-dihydro-2&#39;-deoxyuridine [(5R,6R)-BEEDU], a po‌tential brain-targeted prodrug of 5-ethyl-2&#39;-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&deg;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&#39; excretion into urine, after injection of [4 C]‌EDU, was much faster than that after injection of [4- C]-(5R,6R)-BEEDU. 5-Ethyl-2-deoxyuridine, Dihydro prodrugs, Herpes Simplex Virus, Brain-targeted 105 113 http://ibj.pasteur.ac.ir/browse.php?a_code=A-10-1-430&slc_lang=en&sid=1 Majid Cheraghali مجید چراغعلی Yes Rakesh Kumar Leonard I. Wiebe No Kevin W. Morin Edward E. Knaus No Edward E. Knaus Kevin W. Morin No Leonard I. Wiebe Rakesh Kumar No