A series of 5′‐O‐ acyl derivatives (2a‐e) of 5‐ethyl‐2′‐deoxyuridine (EDU, EtUdR) were prepared by direct acylation of the parent nucleoside 1 in pyridine/N,N‐dimethylformamide (DMF). These compounds, designed as prodrugs of 1, offer a wider range of solubilities and lipophilicities than 1. The antiviral activities (against herpes simplex virus types 1 and 2) of all compounds were determined in primary rabbit kidney (PRK) cell cultures.

1) (EDU) have been synthesized and tested for their activities against vesicular stomatitis virus, vaccinia virus and various strains of herpes simplex virus type 1 (HSV-1) and herpes simplex virus type 2 (HSV-2) in primary rabbit kidney (PRK) cell cultures. The acyclic nucleoside analogues of EDU exhibited no activity against any of the viruses tested.

A series of forty 5'-ester derivatives of 5-ethyl-2'-deoxyuridine (EDU) have been evaluated for their inhibitory effects on the growth and metabolism of murine leukemia L1210 cells. Several EDU esters proved as potent as EDU in their inhibitory effects on L1210 cell growth (inhibitory dose-50:5-10 micrograms/ml), suggesting that these esters were readily hydrolyzed to release the parent compound EDU. That the EDU esters had to be hydrolyzed first to EDU was further suggested by the dependence of their antiproliferative action on the thymidine kinase activity of the cells. It was further ascertained that EDU and its esters acquired their antiproliferative effects by an interaction with dCTP biosynthesis, possibly at the CDP ribonucleotide reductase step. Under conditions where thymidine was readily incorporated, we were unable to demonstrate any incorporation of EDU into L1210 cell DNA.

Biotransformation of [2-14C]-1-AUyl-3,5-dethyl-6-chloronrac~ and Synthesis of Some Possible Degradation ProductsAfter intravenous application of [2-'4C]-1-allyl-3,5-diethyl-6-chlorouracil in rabbits, the major part of the activity is eliminated in the urine and faeces. The major metabolite has been isolated by thick layer and column chromatography. It was identified as 6,8-diethyl-2-(hydroxymethyl)tetrahydrooxazo-10-[3,2-c]pyrimidine-5,7(4H, 6H)-dione (13) by 'H-NMR and mass spectroscopy and by an independent synthesis. The synthesis of the potential degradation products 2-12 which may also occur as metabolites is described.

Die Titelverbindung 4 wurde durch Umsetzung von 5'-O-Trityl-5-ethyl-2'-desoxyundin mit Thionylchlorid in einer Mischung von Dichlormethan und Pyridin hergestellt. Die Tritylschutzgruppe wurde nach bekannten Verfahren abgespalten. Convenient Synthesis of Bis-3'-&(5-ethyl-2'-deoxyaridine) Sulfoxide (KK-Ro 258)The title compound 4 was prepared by treating 5'-O-trityld-ethyl-2'-deoxyuridine with thionyl chloride in a mixture of dichloromethane and pyridine. The trityl group was removed by standard procedures.