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    • 1. 发明申请
    • 2,4- DIAMINO QUINAZOLINE AND PYRIDOPYRIMIDINE ESTER DERIVATIVES AS DIHYDROFOLATE REDUCTASE INHIBITORS
    • 2,4-二氨基喹唑啉和吡咯烷酮衍生物作为二氢叶酸还原酶抑制剂
    • WO2004020418A1
    • 2004-03-11
    • PCT/GB2003/003714
    • 2003-08-27
    • MELACURE THERAPEUTICS ABPETT, Christopher, PhineasHALLBERG, AndersGRAFFNER-NORDBERG, MalinBOMAN, ArneSEIFERT, Elisabeth
    • HALLBERG, AndersGRAFFNER-NORDBERG, MalinBOMAN, ArneSEIFERT, Elisabeth
    • C07D239/95
    • C07D239/95
    • The invention provides novel compounds of the formula 11: wherein R 1 , R 2 , R 3 and R 4 are independently hydrogen or a group that liberates the free amine in vivo , for example -CO-alkyl, preferably -CO-C 1 -C 3 alkyl or pivalate; or -CO­haloalkyl, preferably -CO-C 1 -C 3 haloalkyl, most preferably -CO-C 1 -C 3 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 R 1 to R 4 are hydrogen, both X and Y are C-H, n is 1 and -(CH 2 ) n - is attached to the bridging oxygen of the ester group W, then m cannot be 0 or 1.
    • 本发明提供式11的新化合物:其中R 1,R 2,R 3和R 4独立地为氢或在体内释放游离胺的基团,例如-CO-烷基,优选-CO-C 1 -C 3烷基或特戊酸酯; 或-CO卤代烷基,优选-CO-C 1 -C 3卤代烷基,最优选-CO-C 1 -C 3氯代烷基; 其中W是; 和@表示连接点,并且其中酯可以位于任一方向上; 其中n和m独立地为0-5; 其中X和Y中的一个但不是二者可以是氮,或X是C-A和/或Y是C-B; 其中A和B独立地选自氢,任选被卤素取代的烷基,电子给体基团如氨基,烷基氨基,二烷基氨基或羟基,或电子受体基团如硝基,氰基,三卤代烷基或酰胺基,烷氧基或卤素; 及其药理学上可接受的盐。 假设当R1至R4为氢时,X和Y均为C-H,n为1, - (CH2)n-连接到酯基W的桥连氧上,则m不能为0或1。