A series of 1-beta-ribofuranosyl-5-halocytosine cyclic 3',5'-monophosphates (1-4) has been prepared. Direct halogenation of cytidine 3',5'-monophosphate (cCMP) yielded the Cl, Br, and I compounds while 5-F-cCMP (1) was obtained on cyclization of the 5'-monophosphate. On in vitro testing of 1-4 against L1210 and P388 leukemias, only 1 showed significant low-level activity (ID50 = 3.1 X 10(-4) mmol/L). Derivatives 2-4 were inactive at 10(-1) mmol/L and also proved to have low viral ratings against a series of RNA and DNA virus strains in vitro. By contrast the 5-F-cCMP showed moderate activity against VV, HSV-1, and HSV-2 strains (VR = 0.6-0.9). Both 5-fluorocytidine and 5-fluorocytidine 5'-monophosphate had marked antiviral activity (VR = 1.0-2.1) with the above viruses as well as with parainfluenza virus type 3. The nucleoside and nucleotide also were more active than 5-F-cCMP against L1210 and P388 cells. However, comparison of the cytotoxicities and antiviral ED50 values of 5-F-cCMP, 5-fluorocytidine 5'-monophosphate, and 5-fluorocytidine suggests a potential therapeutic advantage for 5-F-cCMP. Possible rationales for these activities are discussed in terms of 5-F-cCMP and the corresponding 5'-monophosphate as potential prodrugs and as sources, following enzymatic deamination, of cytotoxic 5-fluorouridine or its 5'-monophosphate.

SUWINIARY d 4 C Labelled 5-alkyluracils w e r e p r e p a r e d b y condensation of t h e diethylacetals of o(-formyl-carbonic a c i d esters with 14C-thiourea. Compounds labelled at 4-C w e r e s y n t h e s i z e d b y condensation of t h e labelled carboxylic a c i d derivatives with thiourea.,&An0 m e r s of 5lalkyl-2'-deoxyuridines w e r e obtained in a fairly good radiochemical yield, Alkyl substituents r a n g e d from methyl to tetradecyl, isopropyl a n d tert--bUtyl. K e y words: 5-alkyluracils1 5-alkyl-2*,deoxyuridines, C 0 2 -exchange 4-14C-labelled, * For Parts I a n d I1 s e e Ref, 3 a n d 4, respectively. 713 036 2-4803/78/0514-0 71380 1 .OO 0 1978 by John Wiley & Sons L t d .714 A. Saabotcs, G. Kmsppa, J. S&i and L. 8tv88

Aus (I) und (III) erhält man die Monophosphate (II), die auf antivirale und Antitumor‐Wirkung getestet werden.