new inhibitors of uridinphosphorylase (urdpase) and dihydrouracildehydrogenase (dhudase)

摘要

Novel compounds are provided that are effective to inhibit the activity of DHUDase or UrdPase. Such compounds have the general formula IMAGE IMAGE where X is S or Se; Y is I, F, Cl, Br, methoxy, benzyl, selenenylphenyl, or thiophenyl, and R1 is an acyclo tail having the general formula IMAGE where R2 is H, CH2 OH or CH2 NH2; R3 is OH, NH2, or OCOCH2CH2CO2H; and R4 is O, S, or CH2. The compounds can be used in pharmaceutical compositions, along with various chemotherapeutic agents to increase the efficacy of the treatment. These compounds can also be used in methods of treating patients by coadministering or sequentially administering the enzyme inhibiting compounds with a chemotherapeutic agent effective to treat cancers, or viral, fungal, bacterial, or parasitic infections. The compounds have further utility in enhancing imaging. Further, they can be administered alone to prevent and/or treat disorders of pyrimidine catabolism and other physiological disorders.