Thiopyrimidine-based compounds and uses thereof

A method for the treatment of a kinase associated disease, wherein said method comprises administering to a subject in need of such treatment a therapeutically effective amount of:

• (a) a compound of formula I:
• wherein:
• X is N and Y is CR3;
• wherein each R3 is independently hydrogen, C1-6alkyl, C2-6alkenyl, hydroxyl, halogen, nitro, substituted or unsubstituted amino, cyano, trifluoromethyl, methoxy, trifluoromethoxy, aryl, or substituted or unsubstituted 5 or 6 membered heterocyclyl containing 1 to 2 N atoms;
• R1 is aryl;
• heterocyclyl;
• C1-6alkyl;
• or aryl substituted with one or more substituents R9 or R;
• wherein each R9 is independently substituted or unsubstituted C1-6alkyl, OH, OC1-6alkyl, CN, SR7, CHO, CO2R7, COR7, CONR5R6, CONR5R7, NR5COR7, NR5R6, or NR5COOR7, or a heterocyclyl optionally substituted with 1 to 4 substituents selected from the group consisting of NH2, CN, OH, CO2R7, CH2CN, and 5 membered N-containing heterocyclyl;
• and
• wherein R5 and R6 are each independently H, C1-6alkyl, C1-6alkylCN, C3-8cycloalkyl, aryl, heterocyclyl, C1-6alkylene, cycloalkyl, substituted or unsubstituted C1-6alkylene, SO2C1-6alkyl, or C1-6alkylene heterocyclyl;
• or
• R5 and R6 together with the nitrogen to which they are attached form a 4 to 8 membered ring having 1 to 3 heteroatoms independently selected from the group consisting of NR8, O, and S(O)m, wherein m is 0, 1, or 2, and wherein the ring may be optionally substituted with C1-6alkyl or NR5R6;
• wherein R8 is H, C1-6alkyl, C2-6alkyleneOH, C2-6alkyleneNR5R6, C3-8cycloalkyl, aryl, heterocyclyl, C1-6alkylenecycloalkyl, C1-6alkylenearyl, C1-6alkyleneheterocyclyl, or C1-6alkyleneCN,
• R7 is H, substituted or unsubstituted C1-6alkyl, substituted or unsubstituted OC1-6alkyl, substituted or unsubstituted SC1-6alkyl, CNOH, C1-6alkyleneCN, substituted or unsubstituted C3-8cycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heterocyclyl,C1-6alkylenecycloalkyl,C1-6alkylenearyl, C1-6alkyleneheterocyclyl, C2-6alkenyl, C2-6alkynyl, NR5R6, C1 6alkyleneNR5R6, or C1-6alkyleneOR5;
• each R is C1-6alkyleneR9 or OC1-6alkyleneR9 (except when R9 is NR5R6 or OC1-6alkyl, then R is OC2-6alkyleneR9);
• or
• R9 and R together with the groups to which they are attached form a substituted or unsubstituted 5 or 6 membered N-containing heterocyclyl;
• W is absent, CO, SO2 or C1-6alkylene;
• R2 is aryl;
• imidazolyl;
• (methylenedioxy)phenyl;
• or aryl substituted with one or more substituents selected from the group consisting of an N-containing 5 or 6 membered heterocyclyl;
• substituted or unsubstituted OC1-6alkyl;
• NR5COR7 wherein in this instance only, R5 is H and R7 is C1-6alkyl, C2-6alkenyl, C2-6alkynyl, CH2CN, or CN;
• NH2;
• halo;
• CO2R7;
• SO2NR5R6;
• NO2;
• NHSO2Me;
• CHOHCF3CH3;
• CH2NHSO2Me;
• OH;
• and SH;
• wherein each alkenyl or alkynyl is optionally substituted with 1 to 3 substituents independently selected from the group consisting of C1-6alkyl, CO2R7, CONR5R6, aryl, heterocyclyl, C1-6alkylene OH, and C1-6alkyleneNH2;
• and
• each heterocyclyl is independently a 5 to 7 membered saturated or unsaturated heterocyclyl having 1 to 4 heteroatoms independently selected from the group consisting of N, O, S, and SO2;
• provided that at least one of R1 and R2 is substituted with a substituent selected from the group consisting of:
• wherein
• D is O or N;
• R10 is H or substituted or unsubstituted C1-4alkyl;
• R11 and R12 are each independently H, substituted or unsubstituted C1-4alkylNR14R15, C1-4alkylOR8, or substituted or unsubstituted aryl, or R11 and R12 are joined to form a substituted or unsubstituted 5 to 8 membered ring optionally containing one or more heteroatoms selected from the group consisting of O, S, SO2, and NR10;
• R13 is OH, OC1-4alkyl, or NR14R15;
• p is 0, 1, 2, 3, or 4;
• and
• R14 and R15 are each independently H, or substituted or unsubstituted C1-4alkyl, or R14 and R15 are joined to form a substituted 3-8 membered ring optionally containing one or more heteroatoms selected from the group consisting of O, S, SO2 and NR10;
• or a salt and/or isomer thereof;
• or
• (b) a pharmaceutical composition comprising a compound of formula I or a salt and/or isomer thereof.