Amide derivatives as PDGFR modulators

1 . A method of modulating PDGF-R, 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, spharmaceutically 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, where

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):

wherein K is

each R k is independently H, halogen, substituted or unsubstituted alkyl, or substituted or unsubstituted alkoxy.

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:

each R 1 is independently H, halogen, substituted or unsubstituted alkyl, —O(substituted or unsubstituted alkyl), —O(substituted or unsubstituted alkenyl), —NR c (O)O(substituted or unsubstituted alkyl), —NR c C(O) (substituted or unsubstituted alkyl), —NR c C(O)(substituted or unsubstituted alkenyl), —C(O)NR c (substituted or unsubstituted alkyl), —C(O)NR c (substituted or unsubstituted alkenyl), —NO 2 , —S(═O)R c , —SR c , C(O) 2 R c , or —C(O)R c ; and

each R 2 is independently H or substituted or unsubstituted alkyl.

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

8 . The method of claim 7 , wherein said compound is selected from the group consisting of:

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

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

10 . The method of claim 9 , wherein said compound corresponds to Formula (VII):

wherein:

each R 1 is independently H, halogen, substituted or unsubstituted alkyl, —O(substituted or unsubstituted alkyl), —O(substituted or unsubstituted alkenyl), —NR c C(O)O(substituted or unsubstituted alkyl), —NR c C(O)(substituted or unsubstituted alkyl), —NR c C(O)(substituted or unsubstituted alkenyl), —C(O)NR c (substituted or unsubstituted alkyl), —C(O)NR c (substituted or unsubstituted alkenyl), —NO 2 , —S(═O)R c , —SR c , C(O) 2 R c , or —C(O)R c ; and

each R 2 is independently H or substituted or unsubstituted alkyl, or two R 2 groups are linked together to form an optionally substituted alkylene.

11 . The method of claim 9 , wherein said compound corresponds to Formula (VIII):

12 . The method of claim 11 , wherein said compound is selected from the group consisting of:

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

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.

14 . The method of claim 13 , wherein T of said compound corresponds to Formula (X):

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.

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

16 . The method of claim 15 , wherein L of said compound is a covalent bond, —C(O)NH(substituted or unsubstituted alkylene), —NHC(O)—, —NHC(O)(substituted or unsubstituted alkylene)-, —NH—, or —O(substituted or unsubstituted alkylene)-.

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

18 . The method of claim 17 , wherein B of said compound is a substituted or unsubstituted five-membered heteroarylene.

19 . The method of claim 18 , wherein said five-membered heteroarylene is substituted or unsubstituted thiophenylene.

20 . The method of claim 19 , wherein said compound is selected from the group consisting of:

21 . The method of claim 18 , wherein B is substituted or unsubstituted imidazolylene.

22 . The method of claim 21 , wherein said compound is selected from the group consisting of:

23 . The method of claim 18 , wherein B is substituted or unsubstituted pyrrolylene.

24 . The method of claim 23 , wherein said compound is selected from the group consisting of:

25 . The method of claim 17 , wherein B of said compound is a substituted or unsubstituted 6-membered arylene or heteroarylene.

26 . The method of claim 25 , wherein B is substituted or unsubstituted phenylene.

27 . The method of claim 26 , wherein said compound is selected from the group consisting of:

28 . The method of claim 25 , wherein B is substituted or unsubstituted pyridinylene or pyridazine.

29 . The method of claim 28 , wherein said compound is selected from the group consisting of:

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

31 . The method of claim 30 , wherein B of said compound is a substituted or unsubstituted six-membered heteroarylene.

32 . The method of claim 31 , wherein said six-membered heteroarylene is substituted or unsubstituted pyrimidinylene.

33 . The method of claim 32 , wherein said compound is selected from the group consisting of:

34 . The method of claim 16 , wherein L of said compound —OCH 2 —.

35 . The method of claim 34 , wherein said compound is selected from the group consisting of:

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

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

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

each of X 1 -X 5 is independently C, CR, N, NR, S, or O, wherein no more than three of X 1 -X 5 is a heteroatom, and no two adjacent ring atoms are O or S; where 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.

38 . The method of claim 37 , wherein said compound corresponds to Formula (XV):

39 . The method of claim 38 , wherein L of said compound is a covalent bond, —C(O)NH—, or —O(substituted or unsubstituted alkylene)-.

40 . The method of claim 39 , wherein

of said compound is selected from the group consisting of:

41 . The method of claim 40 , wherein said compound is selected from the group consisting of:

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

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

each of X 1 -X 5 is independently C, CR, N—O, or N, wherein no more than two of X 1 -X 5 is N, where

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.

43 . The method of claim 42 , wherein said compound corresponds to Formula (XVII):

44 . The method of claim 43 , wherein L is a linker selected from the group consisting of a covalent bond, -(substituted or unsubstituted alkylene), —NHC(O)—, —C(O)NH(substituted or unsubstituted alkylene)-, —NHC(O)(substituted or unsubstituted alkylene)-, —C(O)NH(substituted or unsubstituted alkenylene)-, —NHC(O)(substituted or unsubstituted alkenylene)-, and —O(substituted or unsubstituted alkylene)-,

45 . The method of claim 44 , wherein said compound is:

46 . The method of claim 43 , wherein said compound corresponds to Formula (XVIII):

47 . The method of claim 46 , wherein said compound corresponds to Formula (XIX):

48 . The method of claim 47 , wherein said compound is selected from the group consisting of:

49 . The method of claim 46 , wherein said compound corresponds to Formula (XX):

50 . The method of claim 49 , wherein said compound is selected from the group consisting of:

51 . The method of claim 43 , wherein said compound corresponds to Formula (XXI):

52 . The method of claim 51 , wherein said compound is selected from the group consisting of:

53 . The method of claim 43 , wherein said compound corresponds to Formula (XXII):

54 . The method of claim 53 , wherein said compound is selected from the group consisting of:

55 . The method of claim 43 , wherein said compound corresponds to Formula (XXIII):

56 . The method of claim 55 , wherein said compound is selected from the group consisting of:

57 . The method of claim 43 , wherein said compound corresponds to Formula (XXIV):

58 . The method of claim 57 , wherein said compound is selected from the group consisting of:

59 . The method of claim 43 , wherein said compound corresponds to Formula (XXV):

60 . The method of claim 59 , wherein L of said compound is —OCH 2 — or —OCH 2 CHCH—.

61 . The method of claim 60 , wherein said compound is selected from the group consisting of:

62 . The method of claim 59 , wherein L of said compound is —NHC(O)—.

63 . The method of claim 62 , wherein said compound is selected from the group consisting of:

64 . The method of claim 59 , wherein L of said compound is a covalent bond, substituted or unsubstituted alkylene, —NHC(O)(substituted or unsubstituted alkylene)-, —C(O)NH(substituted or unsubstituted alkylene)-, —C(O)NH(substituted or unsubstituted alkenylene)-, or —NHC(O)(substituted or unsubstituted alkenylene)-.

65 . The method of claim 64 , wherein said compound is selected from the group consisting of:

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

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

each of X 1 -X 5 is independently C, CR, NR, O, S, or N, wherein no more than two of X 1 -X 5 is a hetroatom, and no two adjacent ring atoms are O or S, where

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.

Z 1 is O or S; and

Z 2 is CR 3 or N.

67 . The method of claim 66 , wherein said compound corresponds to Formula (XXVII):

68 . The method of claim 67 , wherein said compound is

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

wherein:

each of L and L 1 is independently 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—;

U is a substituted or unsubstituted cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; and

V is a substituted or unsubstituted cycloalkylene, heterocyclene, arylene, or heteroarylene.

70 . The method of claim 69 , wherein said compound corresponds to Formula (XXIX):

71 . The method of claim 70 , wherein said compound is

72 . The method of claim 70 , wherein said compound corresponds to Formula (XXX):

73 . The method of claim 72 , wherein said compound is selected from the group consisting of:

74 . The method of claim 70 , wherein said compound corresponds to Formula (XXXI):

wherein:

each of X 1 -X 5 is independently C, CR, N, NR, S, or O, wherein no more than three of X 1 -X 5 is a heteroatom, and no two adjacent ring atoms are S or 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.

75 . The method of claim 74 , wherein V is a five-membered hetroarylene group.

76 . The method of claim 75 , wherein U is a substituted or unsubstituted five-membered heteroaryl, substituted or unsubstituted phenyl, or substituted or unsubstituted six-membered heteroaryl.

77 . The method of claim 76 , wherein said compound is selected from the group consisting of:

78 . The method of claim 1 , wherein said compound is selected from the group consisting of:

79 . The method of claim 1 , wherein said compound is selected from the group consisting of:

80 . A method of treating a PDGF-R mediated disease, 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.