Synthesis and cytostatic and antiviral activities of 1-beta-D-ribofuranosyl-5-alkylcytosine (5-alkylcytidine) cyclic 3',5'-monophosphates

: A series of 5-alkylcytidines and their 5'-monophosphates and cyclic 3',5'-monophosphates have been synthesized and evaluated for antiviral and antitumor activity. The 5-alkyl cyclic nucleotides were not cytostatic (ID50 greater than 200 micrograms/mL) against leukemia L1210 cells and a deoxycytidine kinase-deficient subline thereof. Certain of the corresponding nucleosides and their 5'-monophosphates did show activity within the range of 35-162 micrograms/mL, as did the unsubstituted cytidine cyclic 3',5'-monophosphate. No antiviral activity was found for any of the compounds at 400 micrograms/mL. A drug design rationale for utilization of 5-alkylcytidines based on their potential conversion to biologically active 5-alkyl-2'-deoxyuridines is not supported by these experimental findings.