PHOSPHORAMIDATE DERIVATIVES OF 5-FLUORO-2'-DEOXYURIDINE FOR USE IN THE TREATMENT OF CANCER

摘要

Phosphoramidate derivatives of 5-fluoro-2′-deoxyuridine are disclosed for use in the treatment of cancer, especially in the treatment of cancer where the patient shows resistance, for example, in a patient with cells with a lowered level of nucleoside transporter proteins and/or with nucleoside kinase-deficient cells and/or with mycoplasma-infected cells and/or with cells with a raised level of thymidylate synthase.;

主权项

1. A compound of formula (I): wherein Ar is a fused bicyclic aryl moiety or a monocyclic aryl moiety, either of which aryl moieties is carbocyclic or heterocyclic and is optionally substituted; R3 is alkyl, which is optionally substituted; R4 is H or alkoyl; R1 and R2 are independently selected from the group consisting of H and alkyl, or R1 and R2 together form an alkylene chain so as to provide, together with the C atom to which they are attached, a cyclic system, or one of R1 and R2 comprises an alkylene chain attached to N, the H atom attached to N is absent and one of R1 and R2 comprise H or alkyl, any of which said alkyl moieties or alkylene chains is optionally substituted; or a pharmaceutically acceptable salt, ester, salt of such ester, hydrate, solvate, crystalline form, or metabolite thereof, or any other compound which upon administration to a recipient is capable of providing (directly or indirectly) said compound of formula (I), wherein the compound is not a compound having, in combination, Ar as unsubstituted phenyl, R3 as CH3, R4 as H, one of R1 and R2 as H and one of R1 and R2 as CH3.