Thiopyrimidine-based compounds and uses thereof

1. A compound of formula I:

or a salt and/or isomer thereof, 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 4-8 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 , 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 alkyl, 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 .

2. The compound according to 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 compound according to claim 1 , wherein the compound of formula I has the formula Ib

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 compound according to 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 compound according to claim 1 , wherein W is absent, CO or C 1-6 alkylene.

6. The compound according to 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. A process for the preparation of the compound of formula I according to claim 1 which comprises the steps of:

(a) adding S—R 1 wherein R 1 is as defined in claim 1 to a compound of formula II

wherein X, Y and R 3 are as defined in formula I above and LG is a leaving group to prepare a compound of formula III

wherein X, Y, LG, R 1 and R 3 are as defined above; and

(b) coupling the compound of formula III with a source of NH—W—R 2 wherein W and R 2 are as defined in claim 1 .

8. A pharmaceutical composition comprising a compound of claim 1 , or a salt and/or isomer thereof, and a pharmaceutically acceptable carrier.

9. An implant which comprises a compound of claim 1 or a salt and/or isomer thereof.

10. The compound according to claim 1 , wherein a substituent of R 1 is selected from the group consisting of:

wherein

D is O;

R 10 , R 11 and R 12 are each H; and

p is 0.