Urea derivatives as ABL modulators

1 . A method of modulating abl kinase, said method comprising administering an effective amount of a compound corresponding to Formula (IA):

wherein:

M is substituted or unsubstituted heteroaryl, or substituted or unsubstituted aryl;

N is a substituted or unsubstituted aryl, or substituted or unsubstituted hetroaryl; and

K is

Y is O or S;

each R k is independently H, halogen, substituted or unsubstituted alkyl, —OH, substituted or unsubstituted alkoxy, —OC(O)R 2 , —NO 2 , —N(R 2 ) 2 , —SR 2 , —C(O)R 2 , —C(O) 2 R 2 , —C(O)N(R 2 ) 2 , or —N(R 2 )C(O)R 2 ,

each R 2 is independently H, substituted or unsubstituted alkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; or wherein two R 2 groups are linked together by an optionally substituted alkylene; and

each n is independently 0, 1, 2, 3 or 4;

or an active metabolite, or a pharmaceutically acceptable prodrug, isomer, pharmaceutically acceptable salt or solvate thereof.

2 . The method of claim 1 , wherein said compound corresponds to Formula (IB):

wherein:

each Z is independently C, CR 3 , N, NR 3 , O, or S, provided that no more than two Z's are heteroatoms and wherein no two adjacent Z's are O or S,

where R 3 is H, substituted or unsubstituted alkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heteroaryl, or substituted or unsubstituted aryl; and

each R 1 is independently H, halogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkoxy, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, —OR c —OH, —OC(O)R c , —NO 2 , —N(R c ) 2 , —SR c , S(O) j R c where j is 1 or 2, —NR c C(O)R c , —C(O)N(R c ) 2 , —C(O) 2 R c , or —C(O)R c ; or two adjacent R 1 's, are taken together to form a substituted or unsubstituted aryl or heteroaryl,

each R c is independently H, substituted or unsubstituted alkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

3 . The method of claim 2 , wherein said compound corresponds to Formula (I):

4 . The method of claim 3 , wherein said compound corresponds to Formula (II):

5 . The method of claim 4 , wherein said compound corresponds to Formula (III):

wherein Z 1 is CR 3 or N; and Z 2 is O or S.

6 . The method of claim 5 , wherein said compound corresponds to Formula (IV):

wherein:

L is a linker selected from the group consisting of a covalent bond, substituted or unsubstituted alkenylene, substituted or unsubstituted alkylene, —C(O)NH—, —C(O)—, —NH—, —O—, —S—, —O(substituted or unsubstituted alkylene)-, —N(substituted or unsubstituted alkylene)-, —C(O)NH(substituted or unsubstituted alkylene), —C(O)NH(substituted or unsubstituted alkenylene)-, —NHC(O)(substituted or unsubstituted alkylene)-, —NHC(O)(substituted or unsubstituted alkenylene)-, —C(O)(substituted or unsubstituted alkenylene)-, and —NHC(O)(substituted or unsubstituted alkylene)S(substituted or unsubstituted alkylene)C(O)NH—; and

T is a mono-, bi-, or tricyclic, substituted or unsubstituted cycloalkyl, heterocyclyl, aryl, or heteroaryl.

7 . The method of claim 6 , wherein T of said compound corresponds to Formula (V):

wherein A is a substituted or unsubstituted five or six-membered heterocyclyl, aryl, or heteroaryl; and B is a substituted or unsubstituted five or six-membered heterocyclene, arylene, or heteroarylene, wherein A and B together form a fused two ring moiety.

8 . The method of claim 7 , wherein said compound corresponds to Formula (VI):

9 . The method of claim 8 , wherein L of said compound is —O(substituted or unsubstituted alkylene)-, —C(O)NH—, or a covalent bond.

10 . The method of claim 8 , wherein A of said compound is substituted or unsubstituted five or six-membered aryl or heteroaryl; and B of said compound is substituted or unsubstituted five or six-membered arylene or heteroarylene.

11 . The method of claim 10 , wherein said compound corresponds to Formula (VII):

wherein:

each X is independently C, CR, N, NR, or O, wherein no more than three X's is a heteroatom, and no two adjacent ring atoms are O; and

each R is independently H, halogen, substituted or unsubstituted alkyl, —OH, substituted or unsubstituted alkoxy, —OC(O)R d , —NO 2 , —N(R d ) 2 , —SR d , —S(O) j R d where j is 1 or 2, —NR d C(O)R d , —C(O) 2 R d , —C(O)N(R d ) 2 or —C(O)R d , or two adjacent R's are taken together to form a substituted or unsubstituted aryl or hetroaryl, where

each R d is independently H, substituted or unsubstituted alkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl or substituted or unsubstituted heteroaryl.

12 . The method of claim 11 , wherein said compound corresponds to Formula (VIII):

13 . The method of claim 12 , wherein said compound is selected from the group consisting of:

14 . The method of claim 10 , wherein said compound corresponds to Formula (IX):

wherein:

each X is independently C, CR, N, NR, or O, wherein no more than three X's is a heteroatom, and no two adjacent ring atoms are O; and

each R is independently H, halogen, substituted or unsubstituted alkyl, —OH, substituted or unsubstituted alkoxy, —OC(O)R d , —NO 2 , —N(R d ) 2 , —SR d , —S(O) j R d where j is 1 or 2, —NR d C(O)R d , —C(O) 2 R d, —C(O )N(R d ) 2 or —C(O)R d , or two adjacent R's are taken together to form a substituted or unsubstituted aryl or hetroaryl, where

each R d is independently H, substituted or unsubstituted alkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl or substituted or unsubstituted heteroaryl.

15 . The method of claim 14 , wherein said compound corresponds to Formula (X):

16 . The method of claim 15 , wherein said compound corresponds to Formula (XI):

17 . The method of claim 16 , wherein said compound is selected from the group consisting of:

18 . The method of claim 15 , wherein said compound corresponds to Formula (XII):

19 . The method of claim 1 , wherein said abl kinase is mutant T3151 Abl-1 kinase.

20 . A method of treating a disease mediated by abl kinase, said method comprising administering a therapeutically effective amount of a compound corresponding to Formula (IA):

wherein:

M is substituted or unsubstituted heteroaryl, or substituted or unsubstituted aryl;

N is a substituted or unsubstituted aryl, or substituted or unsubstituted hetroaryl; and

K is

Y is O or S;

each R k is independently H, halogen, substituted or unsubstituted alkyl, —OH, substituted or unsubstituted alkoxy, —OC(O)R 2 , —NO 2 , —N(R 2 ) 2 , —SR 2 , —C(O)R 2 , —C(O) 2 R 2 , —C(O)N(R 2 ) 2 , or —N(R 2 )C(O)R 2 ,

each R 2 is independently H, substituted or unsubstituted alkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; or wherein two R 2 groups are linked together by an optionally substituted alkylene; and

each n is independently 0, 1, 2, 3 or 4;

or an active metabolite, or a pharmaceutically acceptable prodrug, isomer, pharmaceutically acceptable salt or solvate thereof.