94427-55-1Relevant academic research and scientific papers
Synthesis and Antitumor and Antiviral Activities of a Series of 1-β-D-Ribofuranosyl-5-halocytosine (5-Halocytidine) Cyclic 3',5'-Monophosphates
Beres, Jozsef,Bentrude, Wesley G.,Kruppa, Gabor,McKernan, Patricia A.,Robins, Roland K.
, p. 418 - 422 (2007/10/02)
A series of 1-β-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*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 cytoxicities 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
