COMPOSITIONS USEFUL FOR TREATING DISORDERS RELATED TO KIT

1 . A method of treating melanoma in a patient in need thereof, wherein the method comprises administering to the patient a therapeutically effective amount of a compound of Formula I:

or a pharmaceutically acceptable salt thereof, wherein

W is selected from hydrogen and

wherein Ring A is selected from monocyclic or bicyclic aryl, monocyclic or bicyclic heteroaryl, cycloalkyl and heterocyclyl;

each X and Y is independently selected from CR 1 and N;

Z is selected from C 1 -C 6 alkyl, cycloalkyl, monocyclic or bicyclic aryl, monocyclic or bicyclic aralkyl, monocyclic or bicyclic heteroaryl, monocyclic or bicyclic heterocyclyl, and monocyclic or bicyclic heterocyclylalkyl; wherein each of C 1 -C 6 alkyl, cycloalkyl, monocyclic or bicyclic aryl, monocyclic or bicyclic aralkyl, monocyclic or bicyclic heteroaryl, monocyclic or bicyclic heterocyclyl, monocyclic and bicyclic heterocyclylalkyl is independently substituted with 0-5 occurrences of R C ;

L is selected from a bond, —(C(R 2 )(R 2 )) m —, —(C 2 -C 6 alkynylene)-, —(C 2 -C 6 alkenylene)-, —(C 1 -C 6 haloalkylene)-, —(C 1 -C 6 heteroalkylene)-, —(C 1 -C 6 hydroxyalkylene)-, —C(O)—, —O—, —S—, —S(O), —S(O) 2 —, —N(R 2 )—, —O—(C 1 -C 6 alkylene)-, —(C 1 -C 6 alkylene)-O—, —N(R 2 )—C(O)—, —C(O)—N(R 2 )—, —(C 1 -C 6 alkylene)-N(R 2 )—, —N(R 2 )—(C 1 -C 6 alkylene)-, —N(R 2 )—C(O)—(C 1 -C 6 alkylene)-, —C(O)—N(R 2 )—(C 1 -C 6 alkylene)-, —N(R 2 )—S(O) 2 —, —S(O) 2 —N(R 2 )—, —N(R 2 )—S(O) 2 —(C 1 -C 6 alkylene)-, and —S(O) 2 —N(R 2 )—(C 1 -C 6 alkylene)-;

each R A and R B is independently selected from C 1 -C 6 alkyl, C 1 -C 6 cycloalkyl, C 1 -C 6 heterocyclyl, halo, C 1 -C 6 haloalkyl, C 1 -C 6 hydroxyalkyl, C 1 -C 6 heteroalkyl, monocyclic or bicyclic aralkyl, —N(R 2 )(R 2 ), cyano, and —OR 2 ;

each R C is independently selected from C 1 -C 6 alkyl, C 1 -C 6 alkynyl, halo, C 1 -C 6 heteroalkyl, C 1 -C 6 haloalkyl, C 1 -C 6 haloalkoxy, C 1 -C 6 hydroxyalkyl, cycloalkyl, monocyclic or bicyclic aryl, monocyclic or bicyclic aryloxy, monocyclic or bicyclic aralkyl, monocyclic or bicyclic heterocyclyl, monocyclic or bicyclic heterocyclylalkyl, nitro, cyano, —C(O)R 2 , —OC(O)R 2 , —C(O)OR 2 , —SR 2 , —S(O) 2 R 2 , —S(O) 2 —N(R 2 )(R 2 ), —(C 1 -C 6 alkylene)-S(O) 2 —N(R 2 )(R 2 ), —N(R 2 )(R 2 ), —C(O)—N(R 2 )(R 2 ), —N(R 2 )(R 2 )—C(O)R 2 , —(C 1 -C 6 alkylene)-N(R 2 )—C(O)R 2 , —NR 2 S(O) 2 R 2 , —P(O)(R 2 )(R 2 ), and —OR 2 ; wherein each of heteroalkyl, haloalkyl, haloalkoxy, alkyl, alkynyl, cycloalkyl, aryl, aryloxy, aralkyl, heterocyclyl, heterocyclylalkyl is independently substituted with 0-5 occurrences of R a ; or 2 R C together with the carbon atom(s) to which they are attached form a cycloalkyl or heterocyclyl ring substituted with 0-5 occurrences of R a ;

each of R D and R F is independently selected from hydrogen, C 1 -C 6 alkyl, C 1 -C 6 cycloalkyl, hydroxyl, halo, C 1 -C 6 alkoxy, C 1 -C 6 haloalkyl, —N(R 2 )(R 2 ), and cyano;

each R 1 is independently selected from hydrogen, C 1 -C 6 alkyl, monocyclic aralkyl, C 1 -C 6 hydroxyalkyl, halo, C 1 -C 6 haloalkyl, —N(R 2 )(R 2 ), and —OR 2 ;

each R 2 is independently selected from hydrogen, hydroxyl, halo, thiol, C 1 -C 6 thioalkyl, —NR″R″, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, C 1 -C 6 haloalkyl, C 1 -C 6 hydroxyalkyl, cycloalkyl, cycloalkylalkyl, heterocyclyl, and heterocyclylalkyl, wherein each of C 1 -C 6 alkyl, cycloalkyl and heterocyclyl is independently substituted with 0-5 occurrences of R b , or 2 R 2 together with the atoms to which they are attached form a cycloalkyl or heterocyclyl ring;

each R a and R b is independently selected from hydrogen, halo, cyano, hydroxyl, C 1 -C 6 alkoxyl, —C(O)R′, C(O)OR′, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 heteroalkyl, C 1 -C 6 hydroxyalkyl, —NR′R′, and cycloalkyl, wherein cycloalkyl is substituted with 0-5 occurrences of R′;

each R′ is hydrogen, hydroxyl, or C 1 -C 6 alkyl;

each R″ is hydrogen, C 1 -C 6 alkyl, —C(O)—C 1 -C 6 alkyl, —C(O)—NR′R′; or —C(S)—NR′R′; and

m, p, and q are each independently 0, 1, 2, 3, or 4.

2 . The method of claim 1 , wherein the compound is a compound of Formula II:

or a pharmaceutically acceptable salt thereof.

3 . The method of claim 1 , wherein the compound is a compound of Formula III:

or a pharmaceutically acceptable salt thereof.

4 . The method of claim 1 , wherein at least one of X and Y is N.

5 . (canceled)

6 . The method of claim 1 , wherein L is —(C(R 2 )(R 2 )) m —.

7 . The method of claim 1 , wherein A is monocyclic or bicyclic aryl.

8 . The method of claim 1 , wherein Z is monocyclic or bicyclic aryl.

9 . The method of claim 1 , wherein Z is monocyclic or bicyclic heteroaryl.

10 . The method of claim 1 , wherein Z is monocyclic heteroaryl.

11 . The method of claim 1 , wherein Z is selected from pyrazolyl, isoxazolyl, thiophenyl, thiazolyl, and pyridyl.

12 . The method of claim 1 , wherein Z is phenyl.

13 . The method of claim 1 , wherein Z is monocyclic or bicyclic heterocyclyl.

14 . The method of claim 1 , wherein R A is fluoro and q is 1.

15 . A method of treating melanoma in a patient in need thereof, wherein the method comprises administering to the patient a therapeutically effective amount of a compound selected from the group consisting of the compounds below, or a pharmaceutically acceptable salt thereof:

Compound

Number

Structure

1

2

4

6

7

8

9

10

11

12

13

14

15

16

17

18

19

20

21

22

23

24

25

26

27

28

29

30

31

32

33

34

35

36

37

38

39

40

41

42

43

44

45

46

47

48

49

50

51

52

53

54

55

56

57

58

59

60

61

62

63

64

65

66

67

68

69

70

71

72

73

74

75

76

77

78

79

80

81

82

83

84

85

86

87

88

89

90

91

92

93

95

96

97

94

98

99

100

101

102

103

104

105

106

107

108

109

110

111

112

113

114

115

116

117

118

119

120

121

122

123

124

16 .- 19 . (canceled)

20 . The method of claim 1 , wherein the patient has a mutation in Exon 17 in KIT.

21 . The method of claim 20 , wherein the patient has a D816 mutation in KIT in Exon 17.

22 . The method of claim 21 , wherein the D816 mutation is D816V.

23 .- 24 . (canceled)

25 . A method of treating systemic mastocytosis in a patient in need thereof, wherein the systemic mastocytosis is selected from aggressive systemic mastocytosis (ASM), SM with associated hematologic non-mast cell lineage disease (SM-AHNMD), and mast cell leukemia, wherein the method comprises administering to the patient once daily

i) 200-300 mg of a compound which is:

or a pharmaceutically acceptable salt thereof, or

ii) a pharmaceutical composition comprising a pharmaceutically acceptable carrier and 200-300 mg of the compound or a pharmaceutically acceptable salt thereof.

26 .- 31 . (canceled)

32 . The method of claim 25 , wherein the patient is administered once daily

i) 200 mg of the compound or a pharmaceutically acceptable salt thereof; or

ii) a pharmaceutical composition comprising a pharmaceutically acceptable carrier and 200 mg of the compound or a pharmaceutically acceptable salt thereof.