METHOTREXATE DERIVATIVES

摘要

Methotrexate conjugates of formula (I) are disclosed as well as their use in the treatment of a disease with an autoimmune component and cancers. A particular example of a compound of formula (I) is methotrexate- gamma -glycine Tris, in which M is methotrexate or an analogue thereof; A=H, CX2-O-R2 or halogen; B=H, CX2-O-R3 or halogen; X is independently H or halogen; n is 0 or greater than or equal to 1; Y is a linker group, and where n is greater than 1, each Y is the same or different; R1, R2, and R3 are the same or different and are either hydrogen, substituted or unsubstituted methyl, ethyl, a saturated or unsaturated fatty acyl group, with the proviso that when n is 0 or 1, and A is CH2-O-R2 and/or B is CH2-O-R3, then R1, R2 and R3 are not selected from a fatty acyl group; with the proviso that when n is greater than or equal to 2, and A is CH2-O-R2 and/or B is CH2-O-R3, and at least one of R1, R2 and R3 is a fatty acyl group, then -[Y]n- is other than -(AA)n- or -Y-(AA)n-1-, where AA is an amino acid.