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US 7,888,330 B2Granted
Phosphoramidate derivatives of FAU
AssigneeWayne State University
InventorsAnthony F. Shields, Jiri Zemlicka, Sridhar Nimmagadda
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Abstract
The present invention provides phosphoramidate derivatives of a furanosyluracil analog, FAU, that can effectively deliver FAU monophosphate, or a derivative thereof, intracellularly. FAU-Phosphoramidate diesters can bypass the first step of phosphorylation and be activated intracellularly so as to be converted to nucleoside monophosphates. This results in improved formation of nucleoside triphosphates, and higher incorporation into DNA. The compounds of the invention can be used to treat cancer.
Claims18
A compound of formula I:
- wherein
- R1 is H, F, or (C1-C4)alkyl;
- X is F;
- R4 is phenyl, optionally substituted with 1-3 nitro, 1-5 halo, 1-3 (C1-C6)alkyl, 1-2 CF3 groups, or a combination thereof;
- R2 and R3 are individually H or (C1-C6)alkyl optionally substituted with 1 or 2 hydroxy, (C1-C6)alkoxy, (C1-C6)alkylthio, phenyl, (C6-C12)aryloxy, cyano, (C1-C6)alkoxycarbonyl, amido, (C1-C6)alkyl-amido, (C1-C6)alkylsulfonyl, (C6-C12)arylsulfonyl, (C1-C6)perfluoroalkyl-sulfonyl, (C1-C6)alkylsulfinyl, and (C6-C12)arylsulfinyl, or R2 and R3 taken together with N are a 5- or 6-membered heteroaryl or heterocyclic ring optionally containing 1 or 2 additional S, N, or O atoms, wherein N is substituted with R5, and R5 is H, O, (C1-C4)alkyl, phenyl, or benzyl;
- with the proviso that one of R2 and R3 is not H;
- or a pharmaceutically acceptable salt thereof.
4 more elements
Dependencies are inferred from the claim text.