2,4- DIAMINO QUINAZOLINE AND PYRIDOPYRIMIDINE ESTER DERIVATIVES AS DIHYDROFOLATE REDUCTASE INHIBITORS

摘要

The invention provides novel compounds of the formula 11: wherein R1, R2, R3 and R4 are independently hydrogen or a group that liberates the free amine in vivo, for example -CO-alkyl, preferably -CO-C1-C3 alkyl or pivalate; or -CO­haloalkyl, preferably -CO-C1-C3 haloalkyl, most preferably -CO-C1-C3 chloroalkyl; wherein W is; and @ denotes the points of attachment and wherein the ester can be located in either direction; wherein n and m are independently 0-5; wherein one but not both of X and Y can be nitrogen, or X is C-A and/or Y is C-B; wherein A and B are independently selected from hydrogen, alkyl optionally substituted with a halogen, an electron donor group such as amino, alkylamino, dialkylamino or hydroxy, or an electron acceptor group such as nitro, cyano, trihaloalkyl or amido, alkoxy or halogen; and pharmacologically acceptable salts thereof. Provided that when R1 to R4 are hydrogen, both X and Y are C-H, n is 1 and -(CH2)n- is attached to the bridging oxygen of the ester group W, then m cannot be 0 or 1.