Thiopyrimidine-based compounds and uses thereof

1. 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 CR 3 ;

wherein each R 3 is independently hydrogen, C 1-6 alkyl, C 2-6 alkenyl, 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;

R 1 is aryl; heterocyclyl; C 1-6 alkyl; or aryl substituted with one or more substituents R 9 or R;

wherein each R 9 is independently substituted or unsubstituted C 1-6 alkyl, OH, OC 1-6 alkyl, CN, SR 7 , CHO, CO 2 R 7 , COR 7 , CONR 5 R 6 , CONR 5 R 7 , NR 5 COR 7 , NR 5 R 6 , or NR 5 COOR 7 , or a heterocyclyl optionally substituted with 1 to 4 substituents selected from the group consisting of NH 2 , CN, OH, CO 2 R 7 , CH 2 CN, and 5 membered N-containing heterocyclyl; and

wherein R 5 and R 6 are each independently H, C 1-6 alkyl, C 1-6 alkylCN, C 3-8 cycloalkyl, aryl, heterocyclyl, C 1-6 alkylene, cycloalkyl, substituted or unsubstituted C 1-6 alkylene, SO 2 C 1-6 alkyl, or C 1-6 alkylene heterocyclyl; or

R 5 and R 6 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 NR 8 , O, and S(O) m , wherein m is 0, 1, or 2, and wherein the ring may be optionally substituted with C 1-6 alkyl or NR 5 R 6 ;

wherein R 8 is H, C 1-6 alkyl, C 2-6 alkyleneOH, C 2-6 alkyleneNR 5 R 6 , C 3-8 cycloalkyl, aryl, heterocyclyl, C 1-6 alkylenecycloalkyl, C 1-6 alkylenearyl, C 1-6 alkyleneheterocyclyl, or C 1-6 alkyleneCN,

R 7 is H, substituted or unsubstituted C 1-6 alkyl, substituted or unsubstituted OC 1-6 alkyl, substituted or unsubstituted SC 1-6 alkyl, CNOH, C 1-6 alkyleneCN, substituted or unsubstituted C 3-8 cycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heterocyclyl,C 1-6 alkylenecycloalkyl,C 1-6 alkylenearyl, C 1-6 alkyleneheterocyclyl, C 2-6 alkenyl, C 2-6 alkynyl, NR 5 R 6 , C 1 6 alkyleneNR 5 R 6 , or C 1-6 alkyleneOR 5 ;

each R is C 1-6 alkyleneR 9 or OC 1-6 alkyleneR 9 (except when R 9 is NR 5 R 6 or OC 1-6 alkyl, then R is OC 2-6 alkyleneR 9 ); or

R 9 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, SO 2 or C 1-6 alkylene;

R 2 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 OC 1-6 alkyl; NR 5 COR 7 wherein in this instance only, R 5 is H and R 7 is C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, CH 2 CN, or CN; NH 2 ; halo; CO 2 R 7 ; SO 2 NR 5 R 6 ; NO 2 ; NHSO 2 Me; CHOHCF 3 CH 3 ; CH 2 NHSO 2 Me; OH; and SH;

wherein each alkenyl or alkynyl is optionally substituted with 1 to 3 substituents independently selected from the group consisting of C 1-6 alkyl, CO 2 R 7 , CONR 5 R 6 , aryl, heterocyclyl, C 1-6 alkylene OH, and C 1-6 alkyleneNH 2 ; 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 SO 2;

provided that at least one of R 1 and R 2 is substituted with a substituent selected from the group consisting of:

wherein

D is O or N;

R 10 is H or substituted or unsubstituted C 1-4 alkyl;

R 11 and R 12 are each independently H, substituted or unsubstituted C 1-4 alkylNR 14 R 15 , C 1-4 alkylOR 8 , or substituted or unsubstituted aryl, or R 11 and R 12 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, SO 2 , and NR 10 ;

R 13 is OH, OC 1-4 alkyl, or NR 14 R 15 ;

p is 0, 1, 2, 3, or 4; and

R 14 and R 15 are each independently H, or substituted or unsubstituted C 1-4 alkyl, or R 14 and R 15 are joined to form a substituted 3-8 membered ring optionally containing one or more heteroatoms selected from the group consisting of O, S, SO 2 and NR 10 ;

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.

2. The method of claim 1 , wherein the compound of formula I has the formula Ia

wherein W, R 1 , R 2 and R 3 are as defined in claim 1 .

3. The method of claim 1 , wherein the compound of formula I has the formula lb

wherein W, R 1 and R 3 are as defined in claim 1 , and R′ is H, R, or R 9 , wherein R and R 9 are as defined in claim 1 .

4. The method of claim 1 , wherein the compound of formula I has the formula Ic

wherein W and R 3 are as defined in claim 1 ;

R′ is H, R or R 9 , wherein R and R 9 are as defined in claim 1 , and

R 1 is phenyl substituted as defined in claim 1 .

5. The method of claim 1 , wherein W is absent, CO or C 1-6 alkylene.

6. The method of claim 1 , wherein R 3 is H; C 1-6 alkyl; halo; C 2-6 alkenyl; amino which may be substituted with C 2-6 alkenyl; cyano; nitro; methoxy; aryl; or 5 or 6 membered heterocyclyl containing 1 or 2 N atoms which may be substituted with trimethylcarboxy.

7. The method of claim 1 , wherein the therapeutically effective amount of said compound is administered using an implant, wherein said implant comprises a compound of claim 1 or a pharmaceutical composition comprising a compound of claim 1 .

8. A method of claim 1 , wherein the kinase associated disease is an immunological disease, an inflammatory disease, a hyperproliferative disease, a viral disease, a metabolic disease or a vascular disease.

9. A method for suppressing the immune system of a subject, wherein said method comprises administering a therapeutically effective amount of a compound of claim 1 or a pharmaceutical composition comprising a compound of claim 1 .

10. A method of inhibiting a kinase in a cell, wherein said method comprises contacting the cell with a compound of claim 1 .