C-kit modulators and methods of use

1. A compound for modulating c-Kit activity according to Formula I,

or a pharmaceutically acceptable salt, thereof, wherein,

ring A is:

wherein each Y is independently either ═C(H)— or ═N—; and Z is selected from —O—, —S—, and —N(R 7 )—, provided that the A ring contains at least one annular N, O, or S;

each R 1 is independently selected from —H, halogen, trihalomethyl, —CN, —NO 2 , —OR 4 , —S(O) 0-2 R 4 , —SO 2 N(R 4 )R 4 , —C(═O)N(R 4 )R 4 , —C(═NR 5 )N(R 4 )R 4 , —C(═NR 5 )R 4 , —N(R 4 )SO 2 R 4 , —N(R 4 )C(O)R 4 , —NCO 2 R 4 , —C(═O)R 4 , optionally substituted alkoxy, optionally substituted C 1-6 alkyl, optionally substituted aryl C 1-6 alkyl, optionally substituted heterocyclyl, and optionally substituted heterocyclyl C 1-6 alkyl;

two adjacent of R 1 , together with the annular atoms to which they are attached, can form a five- to six-membered ring containing up to two heteroatoms and optionally substituted with up to three of R 10 ;

L 1 is a single bond;

ring B is phenyl;

each R 2 is independently selected from —H, halogen, trihalomethyl, —CN, —NO 2 , —OR 4 , —N(R 4 )R 4 , —S(O) 0-2 R 4 , —SO 2 N(R 4 )R 4 , —C(═O)N(R 4 )R 4 , —C(═NR 5 )N(R 4 )R 4 , —C(═NR 5 )R 4 , —N(R 4 )SO 2 R 4 , —N(R 4 )C(O)R 4 , —NCO 2 R 4 , —C(═O)R 4 , optionally substituted alkoxy, optionally substituted C 1-6 alkyl, optionally substituted aryl, optionally substituted aryl C 1-6 alkyl, optionally substituted heterocyclyl, and optionally substituted heterocyclyl C 1-6 alkyl;

two adjacent of R 2 , together with the annular atoms to which they are attached, can form a five- to six-membered ring containing up to two heteroatoms and optionally substituted with up to three of R 15 ;

L 2 is selected from —N(H)N(H)C(═O)N(H)—, —CH 2 N(H)C(═O)N(H)—, —CH 2 OC(═O)N(H)—, and —XCH 2 C(═O)N(H)—; wherein X is selected from —O—, —S(O) 0-2 —, and —N(R 7 )—; and any C—H of L 2 is optionally C—R 20 ;

ring C is phenyl;

each R 3 is independently selected from halogen, trihalomethyl, —CN, —NO 2 , —OR 4 , —S(O) 0-2 R 4 , —SO 2 N(R 4 )R 4 , —C(═O)N(R 4 )R 4 , —C(═NR 5 )N(R 4 )R 4 , —C(═NR 5 )R 4 , —N(R 4 )SO 2 R 4 , —N(R 4 )C(O)R 4 , —NCO 2 R 4 , —C(═O)R 4 , optionally substituted alkoxy, optionally substituted C 1-6 alkyl, optionally substituted aryl, optionally substituted aryl C 1-6 alkyl, and optionally substituted heterocyclyl C 1-6 alkyl; provided R 3 is not a cyclic sulfonamide attached to ring C via the nitrogen of said cyclic sulfonamide,

wherein there exists at least one of R 3 that is trihalomethyl;

R 4 is selected from —H, optionally substituted C 1-6 alkyl, optionally substituted aryl, optionally substituted aryl C 1-6 alkyl, substituted heterocyclyl, and optionally substituted heterocyclyl C 1-6 alkyl; or

two of R 4 , when taken together with a common nitrogen to which they are attached, form an optionally substituted five- to seven-membered heterocyclyl, said optionally substituted five- to seven-membered heterocyclyl optionally containing at least one additional heteroatom selected from N, O, S, and P;

R 5 is selected from —H, —CN, —NO 2 , —OR 4 , —S(O) 0-2 R 4 , —CO 2 R 4 , optionally substituted C 1-6 alkyl, optionally substituted C 1-6 alkenyl, and optionally substituted C 1-6 alkynyl;

R 7 is selected from —H, optionally substituted C 1-6 alkyl, —SO 2 N(R 4 )R 4 , —CO 2 R 4 , —C(═O)N(R 4 )R 4 , —C(═NR 5 )N(R 4 )R 4 , —C(═NR 5 )R 4 , —C(═O)R 4 , optionally substituted alkoxy, optionally substituted aryl C 1-6 alkyl, optionally substituted heterocyclyl, and optionally substituted heterocyclyl C 1-6 alkyl; and

each of R 10 , each of R 15 , each of R 20 , and each of R 25 is independently selected from —H, halogen, trihalomethyl, —CN, —NO 2 , —OR 4 , —N(R 4 )R 4 , —S(O) 0-2 R 4 , —SO 2 N(R 4 )R 4 , —CO 2 R 4 , —C(═O)N(R 4 )R 4 , —C(═NR 5 )N(R 4 )R 4 , —C(═NR 5 )R 4 , —N(R 4 )SO 2 R 4 , —N(R 4 )C(O)R 4 , —NCO 2 R 4 , —C(═O)R 4 , optionally substituted alkoxy, optionally substituted C 1-6 alkyl, optionally substituted aryl, optionally substituted aryl C 1-6 alkyl, optionally substituted heterocyclyl, and optionally substituted heterocyclyl C 1-6 alkyl;

provided:

the compound is not one of:

N-(2,3-dichlorophenyl)-2-{[3-(1H-tetrazol-1-yl)phenyl]oxy}acetamide,

N-(4-chloro-3-methylphenyl)-2-{[3-(1H-tetrazol-1-yl)phenyl]oxy}acetamide,

N-(4-bromophenyl)-2-{[3-(1H-tetrazol-1-yl)phenyl]oxy}acetamide

N-(2-fluorophenyl)-2-{[3-(1H-tetrazol-1-yl)phenyl]oxy}acetamide

N-(4-fluorophenyl)-2-{[3-(1H-tetrazol-1-yl)phenyl]oxy}acetamide

2-{[3-(1H-tetrazol-1-yl)phenyl]oxy}-N-[2-(trifluoromethyl)phenyl]acetamide

2-{[3-(1H-tetrazol-1-yl)phenyl]oxy}-N-[3-(trifluoromethyl)phenyl]acetamide

N-[2-chloro-5-(trifluoromethyl)phenyl]-2-{[3-(1H-tetrazol-1-yl)phenyl]oxy}acetamide

N-[4-chloro-3-(trifluoromethyl)phenyl]-2-{[3-(4H-1,2,4-triazol-4-yl)phenyl]oxy}acetamide or

N-(4-chlorophenyl)-2-{[3-(1H-tetrazol-1-yl)phenyl]oxy}acetamide.

2. The compound according to claim 1 , wherein ring C is a phenyl comprising a trifluoromethyl radical meta- to L 2 .

3. The compound according to claim 1 , wherein each of R 3 is independently selected from halogen, trihalomethyl, —OR 4 , —C(═O)R 4 , and optionally substituted C 1-6 alkyl.

4. A compound for modulating c-Kit activity according to the following Formula:

or a pharmaceutically acceptable salt, thereof, wherein,

W is selected from the following:

each of R 27 independently selected from halogen, trihalomethyl, —CN, —NO 2 , —OR 55 , —S(O) 0-2 R 55 , —C(═O)N(R 55 )R 55 , —C(═NR 50 )N(R 55 )R 55 , —C(═NR 50 )R 55 , —N(R 55 )SO 2 R 55 , —N(R 55 )C(O)R 55 , —NCO 2 R 55 , —C(═O)R 55 , optionally substituted alkoxy, optionally substituted C 1-6 alkyl, optionally substituted aryl C 1-6 alkyl, optionally substituted heterocyclyl, and optionally substituted heterocyclyl C 1-6 alkyl;

each Y is independently either ═C(H)— or ═N—;

Z is selected from —O—, —S(O) 0-2 —, and —N(R 7 )—,

provided that the W ring contains at least one annular annular N, O, or S;

E and G are each independently selected from —O—, —S(O) 0-2 —, —C(R 31 )R 32 —, and —N(R 33 )—;

J 1 and J 2 are each independently ═C(H)— or ═N—;

R 7 is selected from —H, optionally substituted C 1-6 alkyl, —SO 2 N(R 4 )R 4 , —CO 2 R 4 , —C(═O)N(R 4 )R 4 , —C(═NR 5 )N(R 4 )R 4 , —C(═NR 5 )R 4 , —C(═O)R 4 , optionally substituted alkoxy, optionally substituted aryl C 1-6 alkyl, optionally substituted heterocyclyl, and optionally substituted heterocyclyl C 1-6 alkyl;

R 4 is selected from —H, optionally substituted C 1-6 alkyl, optionally substituted aryl, optionally substituted aryl C 1-6 alkyl, substituted heterocyclyl, and optionally substituted heterocyclyl C 1-6 alkyl; or

two of R 4 , when taken together with a common nitrogen to which they are attached, form an optionally substituted five- to seven-membered heterocyclyl, said optionally substituted five- to seven-membered heterocyclyl optionally containing at least one additional heteroatom selected from N, O, S, and P;

R 5 is selected from —H, —CN, —NO 2 , —OR 4 , —S(O) 0-2 R 4 , —CO 2 R 4 , optionally substituted C 1-6 alkyl, optionally substituted C 1-6 alkenyl, and optionally substituted C 1-6 alkynyl;

R 26 is independently selected from —H, halogen, trihalomethyl, —CN, —NO 2 , —OR 40 , —N(R 40 )R 40 , —S(O) 0-2 R 40 , —SO 2 N(R 40 )R 40 , —CO 2 R 40 , —C(═O)N(R 40 )R 40 , —C(═NR 50 )N(R 40 )R 40 , —C(═NR 50 )R 40 , —N(R 40 )SO 2 R 40 , —N(R 40 )C(O)R 40 , —NCO 2 R 40 , —C(═O)R 40 , optionally substituted alkoxy, optionally substituted C 1-6 alkyl, optionally substituted aryl, optionally substituted aryl C 1-6 alkyl, optionally substituted heterocyclyl, and optionally substituted heterocyclyl C 1-6 alkyl;

R 30 is independently selected from halogen, trihalomethyl, —CN, —NO 2 , —OR 40 , —S(O) 0-2 R 40 , —SO 2 N(R 40 )R 40 , —C(═O)N(R 40 )R 40 , —C(═NR 50 )N(R 40 )R 40 , —C(NR 50 )R 40 , —N(R 40 )SO 2 R 40 , —N(R 40 )C(O)R 40 , —NCO 2 R 40 , —C(═O)R 40 , optionally substituted alkoxy, optionally substituted C 1-6 alkyl, optionally substituted aryl, optionally substituted aryl C 1-6 alkyl, and optionally substituted heterocyclyl C 1-6 alkyl, wherein there exists at least one of R 30 that is trihalomethyl;

R 31 and R 32 are each independently selected from —H, halogen, trihalomethyl, —NO 2 , —OR 40 , —N(R 40 )R 40 , —S(O) 0-2 R 40 , —SO 2 N(R 40 )R 40 , —CO 2 R 40 , —C(═O)N(R 40 )R 40 , —C(═NR 50 )N(R 40 )R 40 , —C(═NR 50 )R 40 , —N(R 40 )SO 2 R 40 , —N(R 40 )C(O)R 40 , —NCO 2 R 40 , —C(═O)R 40 , optionally substituted alkoxy, optionally substituted C 1-6 alkyl, optionally substituted aryl, optionally substituted aryl C 1-6 alkyl, optionally substituted heterocyclyl, and optionally substituted heterocyclyl C 1-6 alkyl;

R 33 is selected from —H, optionally substituted lower alkyl, —SO 2 N(R 40 )R 40 , —CO 2 R 40 , —C(═O)N(R 40 )R 40 , —C(NR 50 )N(R 40 )R 40 , —C(═NR 50 )R 40 , —C(═O)R 40 , optionally substituted alkoxy, optionally substituted C 1-6 alkyl, optionally substituted aryl, optionally substituted aryl C 1-6 alkyl, and optionally substituted heterocyclyl C 1-6 alkyl;

R 40 is selected from —H, optionally substituted alkoxy, optionally substituted C 1-6 alkyl, optionally substituted aryl, optionally substituted aryl C 1-6 alkyl, optionally substituted heterocyclyl, and optionally substituted heterocyclyl C 1-6 alkyl;

two of R 40 , when taken together with a common nitrogen to which they are attached, form an optionally substituted five- to seven-membered heterocyclyl, said optionally substituted five- to seven-membered heterocyclyl optionally containing at least one additional heteroatom selected from N, O, S, and P;

R 50 is selected from —H, —NO 2 , —OR 40 , —S(O) 0-2 R 40 , —CO 2 R 40 , optionally substituted C 1-6 alkyl, optionally substituted C 1-6 alkenyl, and optionally substituted C 1-6 alkynyl;

R 55 is selected from —H, optionally substituted C 1-6 alkyl, substituted heterocyclyl, and optionally substituted heterocyclyl C 1-6 alkyl; and

two of R 55 , when taken together with a common nitrogen to which they are attached, form an optionally substituted five- to seven-membered heterocyclyl, said optionally substituted five- to seven-membered heterocyclyl optionally containing at least one additional heteroatom selected from N, O, S, and P.

5. The compound according to claim 4 , wherein R 30 is selected from halogen, trihalomethyl, —OR 40 , —C(═O)R 40 , optionally substituted alkoxy, optionally substituted C 1-6 alkyl, optionally substituted aryl, optionally substituted aryl C 1-6 alkyl, and optionally substituted heterocyclyl C 1-6 alkyl, wherein there exists at least one of R 30 that is trifluoromethyl.

6. The compound according to claim 4 , wherein E is selected from —O—, —S(O) 0-2 —, and —NH—; and G is —CH 2 —.

7. The compound according to claim 4 , wherein E is either —CH 2 — or —NH—; and G is selected from —O—, —S—, and —NH—.

8. A compound selected from the following Table:

TABLE 3

Entry

Name

Structure

1

N-[5-chloro-2-(methyloxy)phenyl]-2-{[3- (1H-tetrazol-1-yl)phenyl]oxy}acetamide

4

N-(2-chlorophenyl)-2-{[3-(1H-tetrazol-1- yl)phenyl]oxy}acetamide

5

N-[4-chloro-3-(trifluoromethyl)phenyl]-2- {[3-(1H-tetrazol-1- yl)phenyl]oxy}acetamide

7

N-(3-chloro-2-methylphenyl)-2-{[3-(1H- tetrazol-1-yl)phenyl]oxy}acetamide

8

N-(3-fluorophenyl)-2-{[3-(1H-tetrazol-1- yl)phenyl]oxy}acetamide

9

N-[4-chloro-3-(trifluoromethyl)phenyl]- 2-{[3-(2H-tetrazol-5- yl)phenyl]oxy}acetamide

10

N-(4-chloro-2-fluorophenyl)-2-{[3-(1H- tetrazol-1-yl)phenyl]oxy}acetamide

11

N-(4-bromo-3-methylphenyl)-2-{[3-(1H- tetrazol-1-yl)phenyl]oxy}acetamide

13

N-[4-fluoro-3-(trifluoromethyl)phenyl]-2- {[3-(1H-tetrazol-1- yl)phenyl]oxy}acetamide

14

N-[4-bromo-3-(trifluoromethyl)phenyl]-2- {[3-(1H-tetrazol-1- yl)phenyl]oxy}acetamide

15

N-[4-chloro-3-(trifluoromethyl)phenyl]-2- {[4-(1H-tetrazol-1- yl)phenyl]oxy}acetamide

16

N-[4-chloro-3-(trifluoromethyl)phenyl]-2- {[3-(1H-tetrazol-1- yl)phenyl]oxy}propanamide

17

N-[4-chloro-3-(trifluoromethyl)phenyl]-2- {[3-(5-methyl-1H-tetrazol-1- yl)phenyl]oxy}acetamide

18

N-[4-chloro-3-(trifluoromethyl)phenyl]-2- {[2-methyl-5-(1H-tetrazol-1- yl)phenyl]oxy}acetamide

19

N-(4-chlorophenyl)-N-methyl-2-{[3-(1H- tetrazol-1-yl)phenyl]oxy}acetamide

20

N-[4-chloro-2-(trifluoromethyl)phenyl]-2- {[3-(1H-tetrazol-1- yl)phenyl]oxy}acetamide

23

N-[4-fluoro-3-(trifluoromethyl)phenyl]-2- {[4-(1H-tetrazol-1- yl)phenyl]oxy}acetamide

24

N-[4-chloro-3-(trifluoromethyl)phenyl]-2- {[3-(2-methyl-2H-tetrazol-5- yl)phenyl]oxy}acetamide

25

N-[4-chloro-3-(trifluoromethyl)phenyl]-2- {[2,4-dichloro-5-(1H-tetrazol-1- yl)phenyl]oxy}acetamide

26

N-[4-chloro-3-(trifluoromethyl)phenyl]-2- {[3-(1H-tetrazol-1- yl)phenyl]thio}acetamide

27

N-[4-chloro-3-(trifluoromethyl)phenyl]- N~2~-[3-(1H-tetrazol-1- yl)phenyl]glycinamide

28

N-[4-chloro-3-(trifluoromethyl)phenyl]-2- {[2-(1H-tetrazol-1- yl)phenyl]oxy}acetamide

37

N-[4-chloro-3-(trifluoromethyl)phenyl]-2- [(3-pyridin-4-ylphenyl)oxy]acetamide

38

N-[4-chloro-3-(trifluoromethyl)phenyl]- N~2~-methyl-N~2~-[3-(1H-tetrazol-1- yl)phenyl]glycinamide

49

N-[5-chloro-2,4-bis(methyloxy)phenyl]-2- {[3-(1H-tetrazol-1- yl)phenyl]oxy}acetamide

52

N-[2-(methyloxy)-5- (trifluoromethyl)phenyl]-2-{[3-(1H- tetrazol-1-yl)phenyl]oxy}acetamide

57

1,1-dimethylethyl 2-{3-[(2-{[4-chloro-3- (trifluoromethyl)phenyl]amino}-2- oxoethyl)oxy]phenyl}-1H-pyrrole-1- carboxylate

58

N-[4-chloro-3-(trifluoromethyl)phenyl]-2- {[3-(1H-pyrrol-2-yl)phenyl]oxy}acetamide

59

N-[4-chloro-3-(trifluoromethyl)phenyl]-2- [(3-pyrimidin-5-ylphenyl)oxy]acetamide

60

N-[4-chloro-3-(trifluoromethyl)phenyl]-2- {[3-(1H-1,2,3-triazol-1- yl)phenyl]oxy}acetamide

63

N-[4-chloro-3-(trifluoromethyl)phenyl]-2- [(3-pyridin-3-ylphenyl)oxy]acetamide

68

N-[4-chloro-3-(trifluoromethyl)phenyl]-2- {[3-(3,5-dimethylisoxazol-4- yl)phenyl]oxy}acetamide

69

N-[4-chloro-3-(trifluoromethyl)phenyl]-2- [(3-quinolin-7-ylphenyl)oxy]acetamide

71

N-[4-chloro-3-(trifluoromethyl)phenyl]-2- [3-(1H-tetrazol-1- yl)phenyl]hydrazinecarboxamide

73

N-[4-chloro-3-(trifluoromethyl)phenyl]-2- [(4-pyrimidin-5-ylphenyl)oxy]acetamide

75

N-[4-chloro-3-(trifluoromethyl)phenyl]-N′- {[3-(1H-tetrazol-1-yl)phenyl]methyl}urea

77

N-[4-fluoro-3-(trifluoromethyl)phenyl]- N~2~-[3-(1H-tetrazol-1- yl)phenyl]glycinamide

79

N-[2-fluoro-5-(trifluoromethyl)phenyl]-2- [3-(1H-tetrazol-1- yl)phenyl]hydrazinecarboxamide

80

N-[4-chloro-3-(trifluoromethyl)phenyl]-2- [(4-pyridin-3-ylphenyl)oxy]acetamide

81

N-[4-chloro-3-(trifluoromethyl)phenyl]- N′-[(3-pyrimidin-5-ylphenyl)methyl]urea

82

N-[4-chloro-3-(trifluoromethyl)phenyl]- N′-[(4-pyrimidin-5-ylphenyl)methyl]urea

83

N-[4-chloro-3-(trifluoromethyl)phenyl]- N′-[(4-pyridin-3-ylphenyl)methyl]urea

84

[3-(1H-tetrazol-1-yl)phenyl]methyl [4- chloro-3- (trifluoromethyl)phenyl]carbamate

85

N-[4-fluoro-3-(trifluoromethyl)phenyl]-2- [(4-pyrimidin-5-ylphenyl)oxy]acetamide

86

N~2~-[4-chloro-3- (trifluoromethyl)phenyl]-N-[3-(1H- tetrazol-1-yl)phenyl]glycinamide

87

2-{[4-chloro-3- (trifluoromethyl)phenyl]oxy}-N-[3- (1H-tetrazol-1-yl)phenyl]acetamide

88

N-[4-chloro-3-(trifluoromethyl)phenyl]-2- {[3-methyl-4-(1H-tetrazol-1- yl)phenyl]oxy}acetamide

89

N-[4-chloro-3-(trifluoromethyl)phenyl]-2- {[4-(1H-1,2,3-triazol-1- yl)phenyl]oxy}acetamide

90

N-[4-chloro-3-(trifluoromethyl)phenyl]-2- {[3-fluoro-4-(1H-tetrazol-1- yl)phenyl]oxy}acetamide

91

N-[4-chloro-3-(trifluoromethyl)phenyl]-2- {[2-fluoro-4-(1H-tetrazol-1- yl)phenyl]oxy}acetamide

94

N-[4-fluoro-3-(trifluoromethyl)phenyl]-2- [(4-pyridin-3-ylphenyl)oxy]acetamide

95

2-({4-[2,4-bis(methyloxy)pyrimidin-5- yl]phenyl}oxy)-N-[4-fluoro-3- (trifluoromethyl)phenyl]acetamide

96

2-({4-[2,4-bis(methyloxy)pyrimidin-5- yl]phenyl}oxy)-N-[4-chloro-3- (trifluoromethyl)phenyl]acetamide

97

N-[4-chloro-3-(trifluoromethyl)phenyl]-2- [(4-pyridin-4-ylphenyl)oxy]acetamide

98

N-[4-chloro-3-(trifluoromethyl)phenyl]- N~2~-[3-(methyloxy)-4-(1H-tetrazol-1- yl)phenyl]glycinamide

99

N-[4-chloro-3-(trifluoromethyl)phenyl]- N~2~-[4-(methyloxy)-3-(1H-tetrazol-1- yl)phenyl]glycinamide

100

N-[4-chloro-3-(trifluoromethyl)phenyl]- N~2~-[4-(1H-tetrazol-1- yl)phenyl]glycinamide

101

N-[4-chloro-3-(trifluoromethyl)phenyl]-2- (2,3,5,6-tetrafluoro-4-pyrimidin-5- ylphenyl)hydrazinecarboxamide

102

N-[4-chloro-3-(trifluoromethyl)phenyl]-N′- {[4-(1H-tetrazol-1-yl)phenyl]methyl}urea

103

N-[4-chloro-3-(trifluoromethyl)phenyl]-2- (4-pyrimidin-5- ylphenyl)hydrazinecarboxamide

104

N-[4-chloro-3-(trifluoromethyl)phenyl]-N′- [(3-pyridin-3-ylphenyl)methyl]urea

105

N-[4-chloro-3-(trifluoromethyl)phenyl]-2- methyl-2-{[3-(1H-tetrazol-1- yl)phenyl]oxy}propanamide

106

N-[4-chloro-3-(trifluoromethyl)phenyl]-2- {[4-(1H-tetrazol-1- yl)phenyl]oxy}propanamide

107

N-({4-[2,4-bis(methyloxy)pyrimidin-5- yl]phenyl}methyl)-N′-[4-chloro-3- (trifluoromethyl)phenyl]urea

108

N-[4-chloro-3-(trifluoromethyl)phenyl]- N′-({3-[2-(methyloxy)pyrimidin-5- yl]phenyl}methyl)urea

109

N-[4-chloro-3-(trifluoromethyl)phenyl]- N′-({3-[6-(methyloxy)pyridin-3- yl]phenyl}methyl)urea

110

N-[4-chloro-3-(trifluoromethyl)phenyl]- N′-({4-[2-(methyloxy)pyrimidin-5- yl]phenyl}methyl)urea

111

N-[4-chloro-3-(trifluoromethyl)phenyl]- N′-({4-[6-(methyloxy)pyridin-3- yl]phenyl}methyl)urea

114

N-[4-chloro-3-(trifluoromethyl)phenyl]- N~2~-[3-(2H-tetrazol-5- yl)phenyl]glycinamide

115

N-[4-chloro-3-(trifluoromethyl)phenyl]-2- {[2,6-difluoro-4-(1H-tetrazol-1- yl)phenyl]oxy}acetamide

116

(3-pyridin-3-ylphenyl)methyl [4-chloro-3- (trifluoromethyl)phenyl]carbamate

117

(3-pyrimidin-5-ylphenyl)methyl [4-chloro- 3-trifluoromethyl)phenyl]carbamate

118

(3-pyridin-4-ylphenyl)methyl [4-chloro-3- (trifluoromethyl)phenyl]carbamate

119

N-[4-chloro-3-(trifluoromethyl)phenyl]-2- [4-(1H-tetrazol-1- yl)phenyl]hydrazinecarboxamide

120

N-[4-chloro-3-(trifluoromethyl)phenyl]-2- (4-pyridin-3- ylphenyl)hydrazinecarboxamide

121

(4-pyridin-3-ylphenyl)methyl [4-chloro-3- (trifluoromethyl)phenyl]carbamate

122

(4-pyridin-4-ylphenyl)methyl [4-chloro-3- (trifluoromethyl)phenyl]carbamate

123

(4-pyrimidin-5-ylphenyl)methyl [4-chloro- 3-(trifluoromethyl)phenyl]carbamate

124

N-[4-chloro-3-(trifluoromethyl)phenyl]- N′-[(4-pyridin-4-ylphenyl)methyl]urea

125

N-[4-chloro-3-(trifluoromethyl)phenyl]-2- (3-pyridin-3- ylphenyl)hydrazinecarboxamide

126

N-[4-chloro-3-(trifluoromethyl)phenyl]-2- (3-pyrimidin-5- ylphenyl)hydrazinecarboxamide

127

N-[5-chloro-2,4-bis(methyloxy)phenyl]- N′-[(4-pyrimidin-5-ylphenyl)methyl]urea

128

N-[5-chloro-2,4-bis(methyloxy)phenyl]- N′-[(4-pyridin-3-ylphenyl)methyl]urea

129

(4-pyrimidin-5-ylphenyl)methyl [5-chloro- 2,4-bis(methyloxy)phenyl]carbamate

130

(4-pyridin-3-ylphenyl)methyl [5-chloro- 2,4-bis(methyloxy)phenyl]carbamate

131

1-(4-pyridin-3-ylphenyl)ethyl [4-chloro-3- (trifluoromethyl)phenyl]carbamate

132

1-(4-pyrimidin-5-ylphenyl)ethyl [4-chloro- 3-(trifluoromethyl)phenyl]carbamate

133

N-[5-chloro-2,4-bis(methyloxy)phenyl]- N′-[(3-pyridin-3-ylphenyl)methyl]urea

134

N-[5-chloro-2,4-bis(methyloxy)phenyl]- N′-[(3-pyrimidin-5-ylphenyl)methyl]urea

135

(3-pyridin-3-ylphenyl)methyl [5-chloro- 2,4-bis(methyloxy)phenyl]carbamate

136

(3-pyrimidin-5-ylphenyl)methyl [5-chloro- 2,4-bis(methyloxy)phenyl]carbamate

138

N-[4-fluoro-3-(trifluoromethyl)phenyl]-N′- [(4-pyridin-3-ylphenyl)methyl]urea

143

N-[4-chloro-3-(trifluoromethyl)phenyl]-N′- [1-(4-pyridin-3-ylphenyl)ethyl]urea

144

N-[4-chloro-3-(trifluoromethyl)phenyl]-N′- [1-(4-pyrimidin-5-ylphenyl)ethyl]urea

145

N-[4-chloro-3-(trifluoromethyl)phenyl]-2- {[4-(1H-indol-2-yl)phenyl]oxy}acetamide

147

N-[4-chloro-3-(trifluoromethyl)phenyl]-2- (4-pyridin-4- ylphenyl)hydrazinecarboxamide

148

N-[4-chloro-3-(trifluoromethyl)phenyl]-2- (3-pyridin-4- ylphenyl)hydrazinecarboxamide

149

N-[4-chloro-3-(trifluoromethyl)phenyl]-N′- [(3-pyridin-4-ylphenyl)methyl]urea

150

N-[4-chloro-3-(trifluoromethyl)phenyl]-N′- [(3-quinoxalin-6-ylphenyl)methyl]urea

152

N-[4-chloro-3-(trifluoromethyl)phenyl]-N′- [(4-quinoxalin-6-ylphenyl)methyl]urea

155

[3-(1H-tetrazol-1-yl)phenyl]methyl [3- chloro-4-(methyloxy)phenyl]carbamate

156

N-[3-chloro-4-(methyloxy)phenyl]-N′-{[3- (1H-tetrazol-1-yl)phenyl]methyl}urea

157

N-[4-chloro-3-(trifluoromethyl)phenyl]-2- {[4-(5-hydroxy-1H-tetrazol-1- yl)phenyl]oxy}acetamide

160

N-{[3-(6-chloropyridin-3- yl)phenyl]methyl}-N′-[4-chloro-3- (trifluoromethyl)phenyl]urea

161

N-{[4-(6-chloropyridin-3- yl)phenyl]methyl}-N′-[4-chloro-3- (trifluoromethyl)phenyl]urea

165

N-[4-chloro-3-(trifluoromethyl)phenyl]-N′- {[3-(6-fluoropyridin-3- yl)phenyl]methyl}urea

166

N-[4-chloro-3-(trifluoromethyl)phenyl]-N′- ({3-[2-(methyloxy)pyridin-3- yl]phenyl}methyl)urea

167

N-[4-chloro-3-(trifluoromethyl)phenyl]-N′- {[4-(6-fluoropyridin-3- yl)phenyl]methyl}urea

168

N-[4-chloro-3-(trifluoromethyl)phenyl]-N′- ({4-[2-(methyloxy)pyridin-3- yl]phenyl}methyl)urea

169

N-[4-chloro-3-(trifluoromethyl)phenyl]-N′- {[4-(6-methylpyridin-3- yl)phenyl]methyl}urea

171

N-[4-chloro-3-(trifluoromethyl)phenyl]-N′- {[3-(6-methylpyridin-3- yl)phenyl]methyl}urea

174

[3-(6-methylpyridin-3-yl)phenyl]methyl [4-chloro-3- (trifluoromethyl)phenyl]carbamate

177

(3-pyrazin-2-ylphenyl)methyl [4-chloro-3- (trifluoromethyl)phenyl]carbamate

179

N-{[3-(6-acetylpyridin-3- yl)phenyl]methyl}-N′-[4-chloro-3- (trifluoromethyl)phenyl]urea

180

N-[4-chloro-3-(trifluoromethyl)phenyl]-N′- {[3-(6-cyanopyridin-3- yl)phenyl]methyl}urea

185

[3-(7H-pyrrolo[2,3-d]pyrimidin-4- yl)phenyl]methyl [4-chloro-3- (trifluoromethyl)phenyl]carbamate

188

[3-(1H-benzimidazol-2-yl)phenyl]methyl [4-chloro-3- (trifluoromethyl)phenyl]carbamate

190

N-[4-chloro-3-(trifluoromethyl)phenyl]-N′- ({3-[5-(methylthio)pyridin-3- yl]phenyl}methyl)urea

191

[4-(6-methylpyridin-3-yl)phenyl]methyl [4-chloro-3- (trifluoromethyl)phenyl]carbamate

194

(4-pyrazin-2-ylphenyl)methyl [4-chloro-3- (trifluoromethyl)phenyl]carbamate

195

[4-(7H-pyrrolo[2,3-d]pyrimidin-4- yl)phenyl]methyl [4-chloro-3- (trifluoromethyl)phenyl]carbamate

200

(3-pyridin-3-ylphenyl)methyl [5-chloro-2- (methyloxy)phenyl]carbamate

201

[4-(1H-tetrazol-1-yl)phenyl]methyl [4- chloro-3- (trifluoromethyl)phenyl]carbamate

202

(3-pyrimidin-5-ylphenyl)methyl [5-chloro- 2-(methyloxy)phenyl]carbamate

213

N-[4-chloro-3-(trifluoromethyl)phenyl]-N′- {[3-(1H-pyrazol-4-yl)phenyl]methyl}urea

214

N-[4-chloro-3-(trifluoromethyl)phenyl]-N′- {[4-(1H-pyrazol-4-yl)phenyl]methyl}urea

215

[3-(2-piperazin-1-ylpyrimidin-5- yl)phenyl]methyl [4-chloro-3- (trifluoromethyl)phenyl]carbamate

216

[4-(2-piperazin-1-ylpyrimidin-5- yl)phenyl]methyl [4-chloro-3- (trifluoromethyl)phenyl]carbamate

217

N-{[3-(2-chloropyridin-3- yl)phenyl]methyl}-N′-[4-chloro-3- (trifluoromethyl)phenyl]urea

218

N-{[4-(2-chloropyridin-3- yl)phenyl]methyl}-N′-[4-chloro-3- (trifluoromethyl)phenyl]urea

219

N-[4-chloro-3-(trifluoromethyl)phenyl]- N′-{[3-(2-fluoropyridin-3- yl)phenyl]methyl}urea

220

N-[4-chloro-3-(trifluoromethyl)phenyl]- N′-{[4-(2-fluoropyridin-3- yl)phenyl]methyl}urea

221

[3-(1H-tetrazol-1-yl)phenyl]methyl [3- (trifluoromethyl)phenyl]carbamate

224

N-[4-chloro-3-(trifluoromethyl)phenyl]- N′-({3-[5-(methylthio)pyridin-2- yl]phenyl}methyl)urea

225

[3-(2,6-dimethylpyridin-3- yl)phenyl]methyl [4-chloro-3- (trifluoromethyl)phenyl]carbamate

226

{3-[5-(methyloxy)pyridin-3- yl]phenyl}methyl [4-chloro-3- (trifluoromethyl)phenyl]carbamate

229

N-[4-chloro-3-(trifluoromethyl)phenyl]-N′- [(3-isoquinolin-4-ylphenyl)methyl]urea

230

N-[4-chloro-3-(trifluoromethyl)phenyl]-N′- [(4-isoquinolin-4-ylphenyl)methyl]urea

232

[3-(1H-pyrazol-4-yl)phenyl]methyl [4- chloro-3- (trifluoromethyl)phenyl]carbamate

233

[4-(1H-pyrazol-4-yl)phenyl]methyl [4- chloro-3- (trifluoromethyl)phenyl]carbamate

9. A pharmaceutical composition comprising the compound according to claim 1 and a pharmaceutically acceptable carrier.

10. A method for modulating the in-vivo activity of a kinase, the method comprising administering to a subject an effective amount of the compound according to claim 1 .

11. The method according to claim 10 , wherein the kinase is c-Kit.

12. The method according to claim 11 , wherein modulating the in vivo activity of c-Kit comprises inhibition of c-Kit.

13. A method of treating rheumatoid arthritis, graft-host diseases, multiple sclerosis, psoriasis; artheroscrosis, myocardioinfarction, ischemia, stroke, restenosis; interbowel diseases, osteoarthritus, macular degeneration, or diabetic retinopathy, the method comprising administering, to a mammal in need thereof, a therapeutically effective amount of the compound or the pharmaceutical composition as described in claim 1 .

14. A method of screening for modulators of c-Kit, the method comprising combining the compound according to claim 1 and at least one candidate agent and determining the effect of the candidate agent on c-Kit activity.

15. A method of inhibiting proliferative activity in a cell, the method comprising administering an effective amount of a composition comprising the compound according to claim 1 to a cell or a plurality of cells.