IP Library › Granted Patent US 8,349,848
Granted Patent B2
US 8,349,848 · App. 12/266,259 · Granted Jan 8, 2013

Pyrrolo[3,2-D]pyrimidines that are selective antagonists of A

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Quick Facts
Patent No.
US 8,349,848
App. No.
12/266,259
Granted
Jan 8, 2013
Kind
B2
Abstract

The present invention provides compounds of the following formula and pharmaceutical compositions that are selective antagonists of A 2B adenosine receptors (ARs). These compounds and compositions are useful as pharmaceutical agents.

Claims (4883)

1. A method for inhibiting, relieving and/or ameliorating asthma, allergies by A 2B antagonism, sinusitis or allergic rhinitis in a mammal comprising administering to the mammal an effective amount of a compound of formula I or a stereoisomer or a pharmaceutically acceptable salt thereof:

wherein:

R is selected from: H, OH, C 1-6 alkyl, halo-C 1-8 alkyl, C 3-6 alkenyl, C 3-6 alkynyl, (C 3-8 cycloalkyl)C 1-8 alkylene, (C 4-10 heterocycle)C 1-8 alkylene, (C 6-10 aryl)C 1-8 alkylene, and (C 5-10 heteroaryl)C 1-8 alkylene, wherein R optionally is substituted with 1 R d ;

R d is independently selected from: F, Cl, Br, I, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, OC 1-6 alkyl, NO 2 , —CN, CF 3 , and OCF 3 ;

R 1 and R 2 are independently selected from: H, C 1-8 alkyl, C 3-8 alkenyl, C 3-8 alkynyl, C 1-8 alkoxy, C 3-8 cycloalkyl, (C 3-8 cycloalkyl)C 1-4 alkylene, C 4-10 heterocycle, (C 4-10 heterocycle)C 1-8 alkylene, C 6-10 aryl, (C 6-10 aryl)C 1-8 alkylene, C 5-10 heteroaryl, and (C 5-10 heteroaryl)C 1-8 alkylene, wherein R 1 and R 2 are independently optionally substituted with 1-2 R 1a ;

R 1a is independently selected from: F, Cl, Br, I, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, —(CH 2 ) a OR a , —(CH 2 ) a NR a R a , —(CH 2 ) a NHOH, —(CH 2 ) a NR a NR a R a , —(CH 2 ) a NO 2 , —(CH 2 ) a CN, —(CH 2 ) a CO 2 R a , —(CH 2 ) a C(O)R a , —(CH 2 ) a OC(O)R a , —(CH 2 ) a CONR a R a , CF 3 , and OCF 3 ;

R a is independently selected from: H, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-8 cycloalkyl, (C 3-8 cycloalkyl)C 1-8 alkylene, C 4-10 heterocycle, (C 4-10 heterocycle)C 1-8 alkylene, C 6-10 aryl, (C 6-10 aryl)C 1-8 alkylene, C 5-10 heteroaryl, and (C 5-10 heteroaryl)C 1-8 alkylene, wherein the alkyl is optionally interrupted with 1-2 heteroatoms selected from the group consisting of —O—, —S(O) P — and —NR b —;

R b is independently selected from the group consisting of H, C 1-6 alkyl, and benzyl;

R 3 is selected from: OH, C 1-8 alkoxy, NR 3a R 3b , C 3-8 cycloalkyl, C 4-10 heterocycle, C 6-10 aryl, and C 5-10 heteroaryl, wherein the cycloalkyl, heterocycle, aryl, and heteroaryl are optionally substituted with 1-2 R 3c ;

R 3a and R 3b are independently selected from: C 1-8 alkyl, C 2-8 alkenyl, C 2-8 alkynyl, phenyl, and benzyl;

R 3c is independently selected from: F, Cl, Br, I, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, —(CH 2 ) a OR a , —(CH 2 ) a NR a R a , —(CH 2 ) a NHOH, —(CH 2 ) a NR a NR a R a , —(CH 2 ) a NO 2 , —(CH 2 ) a CN, —(CH 2 ) a CO 2 R a , —(CH 2 ) a C(O)R a , —(CH 2 ) a OC(O)R a , —(CH 2 ) a CONR a R a , CF 3 , and OCF 3 ;

X is selected from: (CH 2 ) q , (CH 2 ) r C(O), and (CH 2 ) r C(O)NR 4 ;

R 4 is selected from: H, C 1-4 alkyl, C 1-4 alkoxy, and C 1-4 haloalkyl;

Y is selected from: 5-10 membered heteroaryl and 6-10 membered aryl, wherein Y is optionally substituted with 1-4 Y 1 ;

Y 1 is independently selected from: F, Cl, Br, I, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, —(CH 2 ) a OR a , —(CH 2 ) a NR a R a , —(CH 2 ) a NHOH, —(CH 2 ) a NR a NR a R a , —(CH 2 ) a NO 2 , —(CH 2 ) a CN, —(CH 2 ) a CO 2 R a , —(CH 2 ) a C(O)R a , —(CH 2 ) a OC(O)R a , —(CH 2 ) a CONR a R a , CF 3 , and OCF 3 ;

a is independently selected from the group consisting of 0, 1, and 2;

n is independently selected from: 1, 2, and 3;

p is independently selected from: 0, 1, and 2;

q is independently selected from 1, 2, 3, and 4; and,

r is independently selected from 0, 1, 2, and 3.

2. The method according to claim 1 , wherein the compound is of formula II or a stereoisomer or a pharmaceutically acceptable salt thereof:

wherein:

R is selected from: H and C 1-4 alkyl;

R 1 and R 2 are independently selected from: H, C 1-4 alkyl, C 3-4 alkenyl, C 3-4 alkynyl, C 3-6 cycloalkyl, (C 3-6 cycloalkyl)C 1-2 alkylene, C 5-6 heterocycle, (C 5-6 heterocycle)C 1-2 alkylene, C 6-10 aryl, (C 6-10 aryl)C 1-2 alkylene, C 5-10 heteroaryl, and (C 5-10 heteroaryl)C 1-2 alkylene, wherein R 1 and R 2 are independently optionally substituted with 1-2 R 1a ;

R 1a is independently selected from: F, Cl, Br, I, C 1-4 alkyl, OR a , NR a R a , NO 2 , —CN, CO 2 R a , C(O)R a , OC(O)R a , CONR a R a , CF 3 , and OCF 3 ;

R 3 is selected from: OCH 3 , OCH 2 CH 3 , NR 3a R 3b , C 3-6 cycloalkyl, and C 5-6 heterocycle, wherein the cycloalkyl and heterocycle are optionally substituted with 1-2 R 3c ;

R 3a and R 3b are independently selected from: C 1-4 alkyl, phenyl, and benzyl;

R 3c is independently selected from: F, Cl, Br, I, C 1-4 alkyl, OR a , NR a R a , NO 2 , —CN, CO 2 R a , C(O)R a , OC(O)R a , CONR a R a , CF 3 , and OCF 3 ;

Y is selected from: 5-6 membered heteroaryl and phenyl, wherein Y is optionally substituted with 1-2 Y 1 ;

Y 1 is independently selected from: F, Cl, Br, I, C 1-4 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, OR a , NR a R a , NO 2 , —CN, CO 2 R a , C(O)R a , OC(O)R a , CONR a R a , CF 3 , and OCF 3 ; and,

R a is independently selected from: H, C 1-4 alkyl, C 3-6 cycloalkyl, phenyl, and benzyl.

3. The method according to claim 2 , wherein:

R is H;

R 1 and R 2 are independently selected from: n-propyl, cyclopropylmethyl, and cyclobutyl;

R 3 is selected from: cyclopropyl, cyclobutyl, N-pyrrolidino, N-piperidino, N-piperazino, and N-morpholino;

Y is selected from: pyridyl and pyrimidyl, wherein Y is optionally substituted with 1-2 Y 1 ; and,

Y 1 is independently selected from: F, Cl, CH 3 , OCH 3 , NO 2 , —CN, and CF 3 .

4. The method according to claim 3 , wherein:

R 1 is selected from: n-propyl and cyclopropylmethyl; and,

R 2 is n-propyl.

5. The method according to claim 3 , wherein:

R 1 is n-propyl; and,

R 2 is n-propyl.

6. The method according to claim 1 , wherein the compound is of formula IV or a stereoisomer or a pharmaceutically acceptable salt thereof:

wherein:

R is selected from: H and C 1-4 alkyl;

R 1 and R 2 are independently selected from: H, C 1-4 alkyl, C 3-4 alkenyl, C 3-4 alkynyl, C 3-6 cycloalkyl, (C 3-6 cycloalkyl)C 1-2 alkylene, C 5-6 heterocycle, (C 5-6 heterocycle)C 1-2 alkylene, C 6-10 aryl, (C 6-10 aryl)C 1-2 alkylene, C 5-10 heteroaryl, and (C 5-10 heteroaryl)C 1-2 alkylene, wherein R 1 and R 2 are independently optionally substituted with 1-2 R 1a ;

R 1a is independently selected from: F, Cl, Br, I, C 1-4 alkyl, OR a , NR a R a , NO 2 , —CN, CO 2 R a , C(O)R a , OC(O)R a , CONR a R a , CF 3 , and OCF 3 ;

R 3 is selected from: OCH 3 , OCH 2 CH 3 , NR 3a R 3b , C 3-6 cycloalkyl, and C 5-6 heterocycle, wherein the cycloalkyl and heterocycle are optionally substituted with 1-2 R 3c ;

R 3a and R 3b are independently selected from: C 1-4 alkyl, phenyl, and benzyl;

R 3c is independently selected from: F, Cl, Br, I, C 1-4 alkyl, OR a , NR a R a , NO 2 , —CN, CO 2 R a , C(O)R a , OC(O)R a , CONR a R a , CF 3 , and OCF 3 ;

Y is selected from: 5-6 membered heteroaryl and phenyl, wherein Y is optionally substituted with 1-2 Y 1 ;

Y 1 is independently selected from: F, Cl, Br, I, C 1-4 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, OR a , NR a R a , NO 2 , —CN, CO 2 R a , C(O)R a , OC(O)R a , CONR a R a , CF 3 , and OCF 3 ; and,

R a is independently selected from: H, C 1-4 alkyl, C 3-6 cycloalkyl, phenyl, and benzyl.

7. The method according to claim 1 , wherein the compound is of formula V or VI or stereoisomer or a pharmaceutically acceptable salt thereof:

8. The method according to claim 1 , wherein the compound is:

or a pharmaceutically acceptable salt thereof.

9. The method according to claim 1 , wherein the compound is selected from

wherein R, R 2 , R 3 and Y′ are as defined in the following table:

Ex.#

R

R 1

R 2

R 3

Y′

1

H

n-propyl

n-propyl

CH 2 OCH 3

H

2

H

n-propyl

n-propyl

CH 3

H

3

H

n-propyl

n-propyl

CH 2 OH

H

4

H

p-propyl

n-propyl

CH 2 N(CH 3 ) 2

H

5

H

p-propyl

n-propyl

CH 2 -N-piperdinyl

H

6

H

n-propyl

n-propyl

CH 2 -N-morpholinyl

FI

7

H

n-propyl

n-propyl

cyclopropyl

H

8

H

n-propyl

n-propyl

CH 2 cyclopropyl

H

9

H

n-propyl

n-propyl

2-tetrahydrofuranyl

H

10

H

n-propyl

n-propyl

CH 2 -2-tetrahydrofuran

H

11

H

n-propyl

n-propyl

2-tetrahydrothienyl

H

12

H

n-propyl

n-propyl

CH 2 OCH 3

CF 3

13

H

n-propyl

n-propyl

CH 3

CF 3

14

H

n-propyl

n-propyl

CH 2 OH

CF 3

15

H

n-propyl

n-propyl

CH 2 N(CH 3 ) 2

CF 3

16

H

n-propyl

n-propyl

CH 2 -N-piperdinyl

CF 3

17

H

n-propyl

n-propyl

CH 2 -N-morpholinyl

CF 3

18

H

n-propyl

n-propyl

cyclopropyl

CF 3

19

H

n-propyl

n-propyl

CH 2 -cyclopropyl

CF 3

20

H

n-propyl

n-propyl

2-tetrahydrofuranyl

CF 3

21

H

n-propyl

n-propyl

CH 2 -2-tetrahydrofuran

CF 3

22

H

n-propyl

n-propyl

2-tetrahydrothienyl

CF 3

23

H

n-propyl

n-propyl

CH 2 OCH 3

F

24

H

n-propyl

n-propyl

CH 3

F

25

H

n-propyl

n-propyl

CH 2 OH

F

26

H

n-propyl

n-propyl

CH 2 N(CH 3 ) 2

F

27

H

n-propyl

n-propyl

CH 2 -N-piperdinyl

F

28

H

n-propyl

n-propyl

CH 2 -N-morpholinyl

F

29

H

n-propyl

n-propyl

cyclopropyl

F

30

H

n-propyl

n-propyl

CH 2 -cyclopropyl

F

31

H

n-propyl

n-propyl

2-tetrahydrofuranyl

F

32

H

n-propyl

n-propyl

CH 2 -2-tetrahydrofuran

F

33

H

n-propyl

n-propyl

2-tetrahydrothienyl

F

34

H

n-propyl

n-propyl

CH 2 OCH 3

Cl

35

H

n-propyl

n-propyl

CH 3

Cl

36

H

n-propyl

n-propyl

CH 2 OH

Cl

37

H

n-propyl

n-propyl

CH 2 N(CH 3 ) 2

Cl

38

H

n-propyl

n-propyl

CH 2 -N-piperdinyl

Cl

39

H

n-propyl

n-propyl

CH 2 -N-morpholinyl

Cl

40

H

n-propyl

n-propyl

cyclopropyl

Cl

41

H

n-propyl

n-propyl

CH 2 -cyclopropyl

Cl

42

H

n-propyl

n-propyl

2-tetrahydrofuranyl

Cl

43

H

n-propyl

n-propyl

CH 2 -2-tetrahydrofuran

Cl

44

H

n-propyl

n-propyl

2-tetrahydrothienyl

Cl

45

H

n-propyl

n-propyl

CH 2 OCH 3

Br

46

H

n-propyl

n-propyl

CH 3

Br

47

H

n-propyl

n-propyl

CH 2 OH

Br

48

H

n-propyl

n-propyl

CH 2 N(CH 3 ) 2

Br

49

H

n-propyl

n-propyl

CH 2 -N-piperdinyl

Br

50

H

n-propyl

n-propyl

CH 2 -N-morpholinyl

Br

51

H

n-propyl

n-propyl

cyclopropyl

Br

52

H

n-propyl

n-propyl

CH 2 -cyclopropyl

Br

53

H

n-propyl

n-propyl

2-tetrahydrofuranyl

Br

54

H

n-propyl

n-propyl

CH 2 -2-tetrahydrofuran

Br

55

H

n-propyl

n-propyl

2-tetrahydrothienyl

Br

56

H

n-propyl

n-propyl

CH 2 OCH 3

I

57

H

n-propyl

n-propyl

CH 3

I

58

H

n-propyl

n-propyl

CH 2 OH

I

59

H

n-propyl

n-propyl

CH 2 N(CH 3 ) 2

I

60

H

n-propyl

n-propyl

CH 2 -N-piperdinyl

I

61

H

n-propyl

n-propyl

CH 2 -N-morpholinyl

I

62

H

n-propyl

n-propyl

cyclopropyl

I

63

H

n-propyl

n-propyl

CH 2 -cyclopropyl

I

64

H

n-propyl

n-propyl

2-tetrahydrofuranyl

I

65

H

n-propyl

n-propyl

CH 2 -2-tetrahydrofuran

I

66

H

n-propyl

n-propyl

2-tetrahydrothienyl

I

67

H

i-propyl

n-propyl

CH 2 OCH 3

H

68

H

i-propyl

n-propyl

CH 3

H

69

H

i-propyl

n-propyl

CH 2 OH

H

70

H

i-propyl

n-propyl

CH 2 N(CH 3 ) 2

H

71

H

i-propyl

n-propyl

CH 2 -N-piperdinyl

H

72

H

i-propyl

n-propyl

CH 2 -N-morpholinyl

H

73

H

i-propyl

n-propyl

cyclopropyl

H

74

H

i-propyl

n-propyl

CH 2 -cyclopropyl

H

75

H

i-propyl

n-propyl

2-tetrahydrofuranyl

H

76

H

i-propyl

n-propyl

CH 2 -2-tetrahydrofuran

H

77

H

i-propyl

n-propyl

2-tetrahydrothienyl

H

78

H

i-propyl

n-propyl

CH 2 OCH 3

CF 3

79

H

i-propyl

n-propyl

CH 3

CF 3

80

H

i-propyl

n-propyl

CH 2 OH

CF 3

81

H

i-propyl

n-propyl

CH 2 N(CH 3 ) 2

CF 3

82

H

i-propyl

n-propyl

CH 2 -N-piperdinyl

CF 3

83

H

i-propyl

n-propyl

CH 2 -N-morpholinyl

CF 3

84

H

i-propyl

n-propyl

cyclopropyl

CF 3

85

H

i-propyl

n-propyl

CH 2 -cyclopropyl

CF 3

86

H

i-propyl

n-propyl

2-tetrahydrofuranyl

CF 3

87

H

i-propyl

n-propyl

CH 2 -2-tetrahydrofuran

CF 3

88

H

i-propyl

n-propyl

2-tetrahydrothienyl

CF 3

89

H

i-propyl

n-propyl

CH 2 OCH 3

F

90

H

i-propyl

n-propyl

CH 3

F

91

H

i-propyl

n-propyl

CH 2 OH

F

92

H

i-propyl

n-propyl

CH 2 N(CH 3 ) 2

F

93

H

i-propyl

n-propyl

CH 2 -N-piperdinyl

F

94

H

i-propyl

n-propyl

CH 2 -N-morpholinyl

F

95

H

i-propyl

n-propyl

cyclopropyl

F

96

H

i-propyl

n-propyl

CH 2 -cyclopropyl

F

97

H

i-propyl

n-propyl

2-tetrahydrofuranyl

F

98

H

i-propyl

n-propyl

CH 2 -2-tetrahydrofuran

F

99

H

i-propyl

n-propyl

2-tetrahydrothienyl

F

100

H

i-propyl

n-propyl

CH 2 OCH 3

Cl

101

H

i-propyl

n-propyl

CH 3

Cl

102

H

i-propyl

n-propyl

CH 2 OH

Cl

103

H

i-propyl

n-propyl

CH 2 N(CH 3 ) 2

Cl

104

H

i-propyl

n-propyl

CH 2 -N-piperdinyl

Cl

105

H

i-propyl

n-propyl

CH 2 -N-morpholinyl

Cl

106

H

i-propyl

n-propyl

cyclopropyl

Cl

107

H

i-propyl

n-propyl

CH 2 -cyclopropyl

Cl

108

H

i-propyl

n-propyl

2-tetrahydrofuranyl

Cl

109

H

i-propyl

n-propyl

CH 2 -2-tetrahydrofuran

Cl

110

H

i-propyl

n-propyl

2-tetrahydrothienyl

Cl

111

H

i-propyl

n-propyl

CH 2 OCH 3

Br

112

H

i-propyl

n-propyl

CH 3

Br

113

H

i-propyl

n-propyl

CH 2 OH

Br

114

H

i-propyl

n-propyl

CH 2 N(CH 3 ) 2

Br

115

H

i-propyl

n-propyl

CH 2 -N-piperdinyl

Br

116

H

i-propyl

n-propyl

CH 2 -N-morpholinyl

Br

117

H

i-propyl

n-propyl

cyclopropyl

Br

118

H

i-propyl

n-propyl

CH 2 -cyclopropyl

Br

119

H

i-propyl

n-propyl

2-tetrahydrofuranyl

Br

120

H

i-propyl

n-propyl

CH 2 -2-tetrahydrofuran

Br

121

H

i-propyl

n-propyl

2-tetrahydrothienyl

Br

122

H

i-propyl

n-propyl

CH 2 OCH 3

I

123

H

i-propyl

n-propyl

CH 3

I

124

H

i-propyl

n-propyl

CH 2 OH

I

125

H

i-propyl

n-propyl

CH 2 N(CH 3 ) 2

I

126

H

i-propyl

n-propyl

CH 2 -N-piperdinyl

I

127

H

i-propyl

n-propyl

CH 2 -N-morpholinyl

I

128

H

i-propyl

n-propyl

cyclopropyl

I

129

H

i-propyl

n-propyl

CH 2 -cyclopropyl

I

130

H

i-propyl

n-propyl

2-tetrahydrofuranyl

I

131

H

i-propyl

n-propyl

CH 2 -2-tetrahydrofuran

I

132

H

i-propyl

n-propyl

2-tetrahydrothienyl

I

133

H

n-butyl

n-propyl

CH 2 OCH 3

H

134

H

n-butyl

n-propyl

CH 3

H

135

H

n-butyl

n-propyl

CH 2 OH

H

136

H

n-butyl

n-propyl

CH 2 N(CH 3 ) 2

H

137

H

n-butyl

n-propyl

CH 2 -N-piperdinyl

H

138

H

n-butyl

n-propyl

CH 2 -N-morpholinyl

H

139

H

n-butyl

n-propyl

cyclopropyl

H

140

H

n-butyl

n-propyl

CH 2 -cyclopropyl

H

141

H

n-butyl

n-propyl

2-tetrahydrofuranyl

H

142

H

n-butyl

n-propyl

CH 2 -2-tetrahydrofuran

H

143

H

n-butyl

n-propyl

2-tetrahydrothienyl

H

144

H

n-butyl

n-propyl

CH 2 OCH 3

CF 3

145

H

n-butyl

n-propyl

CH 3

CF 3

146

H

n-butyl

n-propyl

CH 2 OH

CF 3

147

H

n-butyl

n-propyl

CH 2 N(CH 3 ) 2

CF 3

148

H

n-butyl

n-propyl

CH 2 -N-piperdinyl

CF 3

149

H

n-butyl

n-propyl

CH 2 -N-morpholinyl

CF 3

150

H

n-butyl

n-propyl

cyclopropyl

CF 3

151

H

n-butyl

n-propyl

CH 2 -cyclopropyl

CF 3

152

H

n-butyl

n-propyl

2-tetrahydrofuranyl

CF 3

153

H

n-butyl

n-propyl

CH 2 -2-tetrahydrofuran

CF 3

154

H

n-butyl

n-propyl

2-tetrahydrothienyl

CF 3

155

H

n-butyl

n-propyl

CH 2 OCH 3

F

156

H

n-butyl

n-propyl

CH 3

F

157

H

n-butyl

n-propyl

CH 2 OH

F

158

H

n-butyl

n-propyl

CH 2 N(CH 3 ) 2

F

159

H

n-butyl

n-propyl

CH 2 -N-piperdinyl

F

160

H

n-butyl

n-propyl

CH 2 -N-morpholinyl

F

161

H

n-butyl

n-propyl

cyclopropyl

F

162

H

n-butyl

n-propyl

CH 2 -cyclopropyl

F

163

H

n-butyl

n-propyl

2-tetrahydrofuranyl

F

164

H

n-butyl

n-propyl

CH 2 -2-tetrahydrofuran

F

165

H

n-butyl

n-propyl

2-tetrahydrothienyl

F

166

H

n-butyl

n-propyl

CH 2 OCH 3

Cl

167

H

n-butyl

n-propyl

CH 3

Cl

168

H

n-butyl

n-propyl

CH 2 OH

Cl

169

H

n-butyl

n-propyl

CH 2 N(CH 3 ) 2

Cl

170

H

n-butyl

n-propyl

CH 2 -N-piperdinyl

Cl

171

H

n-butyl

n-propyl

CH 2 -N-morpholinyl

Cl

172

H

n-butyl

n-propyl

cyclopropyl

Cl

173

H

n-butyl

n-propyl

CH 2 -cyclopropyl

Cl

174

H

n-butyl

n-propyl

2-tetrahydrofuranyl

Cl

175

H

n-butyl

n-propyl

CH 2 -2-tetrahydrofuran

Cl

176

H

n-butyl

n-propyl

2-tetrahydrothienyl

Cl

177

H

n-butyl

n-propyl

CH 2 OCH 3

Br

178

H

n-butyl

n-propyl

CH 3

Br

179

H

n-butyl

n-propyl

CH 2 OH

Br

180

H

n-butyl

n-propyl

CH 2 N(CH 3 ) 2

Br

181

H

n-butyl

n-propyl

CH 2 -N-piperdinyl

Br

182

H

n-butyl

n-propyl

CH 2 -N-morpholinyl

Br

183

H

n-butyl

n-propyl

cyclopropyl

Br

184

H

n-butyl

n-propyl

CH 2 -cyclopropyl

Br

185

H

n-butyl

n-propyl

2-tetrahydrofuranyl

Br

186

H

n-butyl

n-propyl

CH 2 -2-tetrahydrofuran

Br

187

H

n-butyl

n-propyl

2-tetrahydrothienyl

Br

188

H

n-butyl

n-propyl

CH 2 OCH 3

I

189

H

n-butyl

n-propyl

CH 3

I

190

H

n-butyl

n-propyl

CH 2 OH

I

191

H

n-butyl

n-propyl

CH 2 N(CH 3 ) 2

I

192

H

n-butyl

n-propyl

CH 2 -N-piperdinyl

I

193

H

n-butyl

n-propyl

CH 2 -N-morpholinyl

I

194

H

n-butyl

n-propyl

cyclopropyl

I

195

H

n-butyl

n-propyl

CH 2 -cyclopropyl

I

196

H

n-butyl

n-propyl

2-tetrahydrofuranyl

I

197

H

n-butyl

n-propyl

CH 2 -2-tetrahydrofuran

I

198

H

n-butyl

n-propyl

2-tetrahydrothienyl

I

199

H

i-butyl

n-propyl

CH 2 OCH 3

H

200

H

i-butyl

n-propyl

CH 3

H

201

H

i-butyl

n-propyl

CH 2 OH

H

202

H

i-butyl

n-propyl

CH 2 N(CH 3 ) 2

H

203

H

i-butyl

n-propyl

CH 2 -N-piperdinyl

H

204

H

i-butyl

n-propyl

CH 2 -N-morpholinyl

H

205

H

i-butyl

n-propyl

cyclopropyl

H

206

H

i-butyl

n-propyl

CH 2 -cyclopropyl

207

H

i-butyl

n-propyl

2-tetrahydrofuranyl

H

208

H

i-butyl

n-propyl

CH 2 -2-tetrahydrofuran

H

209

H

i-butyl

n-propyl

2-tetrahydrothienyl

H

210

H

i-butyl

n-propyl

CH 2 OCH 3

CF 3

211

H

i-butyl

n-propyl

CH 3

CF 3

212

H

i-butyl

n-propyl

CH 2 OH

CF 3

213

H

i-butyl

n-propyl

CH 2 N(CH 3 ) 2

CF 3

214

H

i-butyl

n-propyl

CH 2 -N-piperdinyl

CF 3

215

H

i-butyl

n-propyl

CH 2 -N-morpholinyl

CF 3

216

H

i-butyl

n-propyl

cyclopropyl

CF 3

217

H

i-butyl

n-propyl

CH 2 -cyclopropyl

CF 3

218

H

i-butyl

n-propyl

2-tetrahydrofuranyl

CF 3

219

H

i-butyl

n-propyl

CH 2 -2-tetrahydrofuran

CF 3

220

H

i-butyl

n-propyl

2-tetrahydrothienyl

CF 3

221

H

i-butyl

n-propyl

CH 2 OCH 3

F

222

H

i-butyl

n-propyl

CH 3

F

223

H

i-butyl

n-propyl

CH 2 OH

F

224

H

i-butyl

n-propyl

CH 2 N(CH 3 ) 2

F

225

H

i-butyl

n-propyl

CH 2 -N-piperdinyl

F

226

H

i-butyl

n-propyl

CH 2 -N-morpholinyl

F

227

H

i-butyl

n-propyl

cyclopropyl

F

228

H

i-butyl

n-propyl

CH 2 -cyclopropyl

F

229

H

i-butyl

n-propyl

2-tetrahydrofuranyl

F

230

H

i-butyl

n-propyl

CH 2 -2-tetrahydrofuran

F

231

H

i-butyl

n-propyl

2-tetrahydrothienyl

F

232

H

i-butyl

n-propyl

CH 2 OCH 3

Cl

233

H

i-butyl

n-propyl

CH 3

Cl

234

H

i-butyl

n-propyl

CH 2 OH

Cl

235

H

i-butyl

n-propyl

CH 2 N(CH 3 ) 2

Cl

236

H

i-butyl

n-propyl

CH 2 -N-piperdinyl

Cl

237

H

i-butyl

n-propyl

CH 2 -N-morpholinyl

Cl

238

H

i-butyl

n-propyl

cyclopropyl

Cl

239

H

i-butyl

n-propyl

CH 2 -cyclopropyl

Cl

240

H

i-butyl

n-propyl

2-tetrahydrofuranyl

Cl

241

H

i-butyl

n-propyl

CH 2 -2-tetrahydrofuran

Cl

242

H

i-butyl

n-propyl

2-tetrahydrothienyl

Cl

243

H

i-butyl

n-propyl

CH 2 OCH 3

Br

244

H

i-butyl

n-propyl

CH 3

Br

245

H

i-butyl

n-propyl

CH 2 OH

Br

246

H

i-butyl

n-propyl

CH 2 N(CH 3 ) 2

Br

247

H

i-butyl

n-propyl

CH 2 -N-piperdinyl

Br

248

H

i-butyl

n-propyl

CH 2 -N-morpholinyl

Br

249

H

i-butyl

n-propyl

cyclopropyl

Br

250

H

i-butyl

n-propyl

CH 2 -cyclopropyl

Br

251

H

i-butyl

n-propyl

2-tetrahydrofuranyl

Br

252

H

i-butyl

n-propyl

CH 2 -2-tetrahydrofuran

Br

253

H

i-butyl

n-propyl

2-tetrahydrothienyl

Br

254

H

i-butyl

n-propyl

CH 2 OCH 3

I

255

H

i-butyl

n-propyl

CH 3

I

256

H

i-butyl

n-propyl

CH 2 OH

I

257

H

i-butyl

n-propyl

CH 2 N(CH 3 ) 2

I

258

H

i-butyl

n-propyl

CH 2 -N-piperdinyl

I

259

H

i-butyl

n-propyl

CH 2 -N-morpholinyl

I

260

H

i-butyl

n-propyl

cyclopropyl

I

261

H

i-butyl

n-propyl

CH 2 -cyclopropyl

I

262

H

i-butyl

n-propyl

2-tetrahydrofuranyl

I

263

H

i-butyl

n-propyl

CH 2 -2-tetrahydrofuran

I

264

H

i-butyl

n-propyl

2-tetrahydrothienyl

I

265

H

cyclobutyl

n-propyl

CH 2 OCH 3

H

266

H

cyclobutyl

n-propyl

CH 3

H

267

H

cyclobutyl

n-propyl

CH 2 OH

H

268

H

cyclobutyl

n-propyl

CH 2 N(CH 3 ) 2

H

269

H

cyclobutyl

n-propyl

CH 2 -N-piperdinyl

H

270

H

cyclobutyl

n-propyl

CH 2 -N-morpholinyl

H

271

H

cyclobutyl

n-propyl

cyclopropyl

H

272

H

cyclobutyl

n-propyl

CH 2 -cyclopropyl

H

273

H

cyclobutyl

n-propyl

2-tetrahydrofuranyl

H

274

H

cyclobutyl

n-propyl

CH 2 -2-tetrahydrofuran

H

275

H

cyclobutyl

n-propyl

2-tetrahydrothienyl

H

276

H

cyclobutyl

n-propyl

CH 2 OCH 3

CF 3

277

H

cyclobutyl

n-propyl

CH 3

CF 3

278

H

cyclobutyl

n-propyl

CH 2 OH

CF 3

279

H

cyclobutyl

n-propyl

CH 2 N(CH 3 ) 2

CF 3

280

H

cyclobutyl

n-propyl

CH 2 -N-piperdinyl

CF 3

281

H

cyclobutyl

n-propyl

CH 2 -N-morpholinyl

CF 3

282

H

cyclobutyl

n-propyl

cyclopropyl

CF 3

283

H

cyclobutyl

n-propyl

CH 2 -cyclopropyl

CF 3

284

H

cyclobutyl

n-propyl

2-tetrahydrofuranyl

CF 3

285

H

cyclobutyl

n-propyl

CH 2 -2-tetrahydrofuran

CF 3

286

H

cyclobutyl

n-propyl

2-tetrahydrothienyl

CF 3

287

H

cyclobutyl

n-propyl

CH 2 OCH 3

F

288

H

cyclobutyl

n-propyl

CH 3

F

289

H

cyclobutyl

n-propyl

CH 2 OH

F

290

H

cyclobutyl

n-propyl

CH 2 N(CH 3 ) 2

F

291

H

cyclobutyl

n-propyl

CH 2 -N-piperdinyl

F

292

H

cyclobutyl

n-propyl

CH 2 -N-morpholinyl

F

293

H

cyclobutyl

n-propyl

cyclopropyl

F

294

H

cyclobutyl

n-propyl

CH 2 -cyclopropyl

F

295

H

cyclobutyl

n-propyl

2-tetrahydrofuranyl

F

296

H

cyclobutyl

n-propyl

CH 2 -2-tetrahydrofuran

F

297

H

cyclobutyl

n-propyl

2-tetrahydrothienyl

F

298

H

cyclobutyl

n-propyl

CH 2 OCH 3

Cl

299

H

cyclobutyl

n-propyl

CH 3

Cl

300

H

cyclobutyl

n-propyl

CH 2 OH

Cl

301

H

cyclobutyl

n-propyl

CH 2 N(CH 3 ) 2

Cl

302

H

cyclobutyl

n-propyl

CH 2 -N-piperdinyl

Cl

303

H

cyclobutyl

n-propyl

CH 2 -N-morpholinyl

Cl

304

H

cyclobutyl

n-propyl

cyclopropyl

Cl

305

H

cyclobutyl

n-propyl

CH 2 -cyclopropyl

Cl

306

H

cyclobutyl

n-propyl

2-tetrahydrofuranyl

Cl

307

H

cyclobutyl

n-propyl

CH 2 -2-tetrahydrofuran

Cl

308

H

cyclobutyl

n-propyl

2-tetrahydrothienyl

Cl

309

H

cyclobutyl

n-propyl

CH 2 OCH 3

Br

310

H

cyclobutyl

n-propyl

CH 3

Br

311

H

cyclobutyl

n-propyl

CH 2 OH

Br

312

H

cyclobutyl

n-propyl

CH 2 N(CH 3 ) 2

Br

313

H

cyclobutyl

n-propyl

CH 2 -N-piperdinyl

Br

314

H

cyclobutyl

n-propyl

CH 2 -N-morpholinyl

Br

315

H

cyclobutyl

n-propyl

cyclopropyl

Br

316

H

cyclobutyl

n-propyl

CH 2 -cyclopropyl

Br

317

H

cyclobutyl

n-propyl

2-tetrahydrofuranyl

Br

318

H

cyclobutyl

n-propyl

CH 2 -2-tetrahydrofuran

Br

319

H

cyclobutyl

n-propyl

2-tetrahydrothienyl

Br

320

H

cyclobutyl

n-propyl

CH 2 OCH 3

I

321

H

cyclobutyl

n-propyl

CH 3

I

322

H

cyclobutyl

n-propyl

CH 2 OH

I

323

H

cyclobutyl

n-propyl

CH 2 N(CH 3 ) 2

I

324

H

cyclobutyl

n-propyl

CH 2 -N-piperdinyl

I

325

H

cyclobutyl

n-propyl

CH 2 -N-morpholinyl

I

326

H

cyclobutyl

n-propyl

cyclopropyl

I

327

H

cyclobutyl

n-propyl

CH 2 -cyclopropyl

I

328

H

cyclobutyl

n-propyl

2-tetrahydrofuranyl

I

329

H

cyclobutyl

n-propyl

CH 2 -2-tetrahydrofuran

I

330

H

cyclobutyl

n-propyl

2-tetrahydrothienyl

I

331

H

cyclopropylmethyl-

n-propyl

CH 2 OCH 3

H

332

H

cyclopropylmethyl-

n-propyl

CH 3

H

333

H

cyclopropylmethyl-

n-propyl

CH 2 OH

H

334

H

cyclopropylmethyl-

n-propyl

CH 2 N(CH 3 ) 2

H

335

H

cyclopropylmethyl-

n-propyl

CH 2 -N-piperdinyl

H

336

H

cyclopropylmethyl-

n-propyl

CH 2 -N-morpholinyl

H

337

H

cyclopropylmethyl-

n-propyl

cyclopropyl

H

338

H

cyclopropylmethyl-

n-propyl

CH 2 -cyclopropyl

H

339

H

cyclopropylmethyl-

n-propyl

2-tetrahydrofuranyl

H

340

H

cyclopropylmethyl-

n-propyl

CH 2 -2-tetrahydrofuran

H

341

H

cyclopropylmethyl-

n-propyl

2-tetrahydrothienyl

H

342

H

cyclopropylmethyl-

n-propyl

CH 2 OCH 3

CF 3

343

H

cyclopropylmethyl-

n-propyl

CH 3

CF 3

344

H

cyclopropylmethyl-

n-propyl

CH 2 OH

CF 3

345

H

cyclopropylmethyl-

n-propyl

CH 2 N(CH 3 ) 2

CF 3

346

H

cyclopropylmethyl-

n-propyl

CH 2 -N-piperdinyl

CF 3

347

H

cyclopropylmethyl-

n-propyl

CH 2 -N-morpholinyl

CF 3

348

H

cyclopropylmethyl-

n-propyl

cyclopropyl

CF 3

349

H

cyclopropylmethyl-

n-propyl

CH 2 -cyclopropyl

CF 3

350

H

cyclopropylmethyl-

n-propyl

2-tetrahydrofuranyl

CF 3

351

H

cyclopropylmethyl-

n-propyl

CH 2 -2-tetrahydrofuran

CF 3

352

H

cyclopropylmethyl-

n-propyl

2-tetrahydrothienyl

CF 3

353

H

cyclopropylmethyl-

n-propyl

CH 2 OCH 3

F

354

H

cyclopropylmethyl-

n-propyl

CH 3

F

355

H

cyclopropylmethyl-

n-propyl

CH 2 OH

F

356

H

cyclopropylmethyl-

n-propyl

CH 2 N(CH 3 ) 2

F

357

H

cyclopropylmethyl-

n-propyl

CH 2 -N-piperdinyl

F

358

H

cyclopropylmethyl-

n-propyl

CH 2 -N-morpholinyl

F

359

H

cyclopropylmethyl-

n-propyl

cyclopropyl

F

360

H

cyclopropylmethyl-

n-propyl

CH 2 -cyclopropyl

F

361

H

cyclopropylmethyl-

n-propyl

2-tetrahydrofuranyl

F

362

H

cyclopropylmethyl-

n-propyl

CH 2 -2-tetrahydrofuran

F

363

H

cyclopropylmethyl-

n-propyl

2-tetrahydrothienyl

F

364

H

cyclopropylmethyl-

n-propyl

CH 2 OCH 3

Cl

365

H

cyclopropylmethyl-

n-propyl

CH 3

Cl

366

H

cyclopropylmethyl-

n-propyl

CH 2 OH

Cl

367

H

cyclopropylmethyl-

n-propyl

CH 2 N(CH 3 ) 2

Cl

368

H

cyclopropylmethyl-

n-propyl

CH 2 -N-piperdinyl

Cl

369

H

cyclopropylmethyl-

n-propyl

CH 2 -N-morpholinyl

Cl

370

H

cyclopropylmethyl-

n-propyl

cyclopropyl

Cl

371

H

cyclopropylmethyl-

n-propyl

CH 2 -cyclopropyl

Cl

372

H

cyclopropylmethyl-

n-propyl

2-tetrahydrofuranyl

Cl

373

H

cyclopropylmethyl-

n-propyl

CH 2 -2-tetrahydrofuran

Cl

374

H

cyclopropylmethyl-

n-propyl

2-tetrahydrothienyl

Cl

375

H

cyclopropylmethyl-

n-propyl

CH 2 OCH 3

Br

376

H

cyclopropylmethyl-

n-propyl

CH 3

Br

377

H

cyclopropylmethyl-

n-propyl

CH 2 OH

Br

378

H

cyclopropylmethyl-

n-propyl

CH 2 N(CH 3 ) 2

Br

379

H

cyclopropylmethyl-

n-propyl

CH 2 -N-piperdinyl

Br

380

H

cyclopropylmethyl-

n-propyl

CH 2 -N-morpholinyl

Br

381

H

cyclopropylmethyl-

n-propyl

cyclopropyl

Br

382

H

cyclopropylmethyl-

n-propyl

CH 2 -cyclopropyl

Br

383

H

cyclopropylmethyl-

n-propyl

2-tetrahydrofuranyl

Br

384

H

cyclopropylmethyl-

n-propyl

CH 2 -2-tetrahydrofuran

Br

385

H

cyclopropylmethyl-

n-propyl

2-tetrahydrothienyl

Br

386

H

cyclopropylmethyl-

n-propyl

CH 2 OCH 3

I

387

H

cyclopropylmethyl-

n-propyl

CH 3

I

388

H

cyclopropylmethyl-

n-propyl

CH 2 OH

I

389

H

cyclopropylmethyl-

n-propyl

CH 2 N(CH 3 ) 2

I

390

H

cyclopropylmethyl-

n-propyl

CH 2 -N-piperdinyl

I

391

H

cyclopropylmethyl-

n-propyl

CH 2 -N-morpholinyl

I

392

H

cyclopropylmethyl-

n-propyl

cyclopropyl

I

393

H

cyclopropylmethyl-

n-propyl

CH 2 -cyclopropyl

I

394

H

cyclopropylmethyl-

n-propyl

2-tetrahydrofuranyl

I

395

H

cyclopropylmethyl-

n-propyl

CH 2 -2-tetrahydrofuran

I

396

H

cyclopropylmethyl-

n-propyl

2-tetrahydrothienyl

I

or a pharmaceutically acceptable salt thereof.

10. A method for inhibiting, relieving and/or ameliorating ischemia/reprefusion injuries in a mammal, comprising administering to the mammal an effective amount of a compound of formula I or a stereoisomer or a pharmaceutically acceptable salt thereof:

wherein:

R is selected from: H, OH, C 1-6 alkyl, halo-C 1-8 alkyl, C 3-6 alkenyl, C 3-6 alkynyl, (C 3-8 cycloalkyl)C 1-8 alkylene, (C 4-10 heterocycle)C 1-8 alkylene, (C 6-10 aryl)C 1-8 alkylene, and (C 5-10 heteroaryl)C 1-8 alkylene, wherein R optionally is substituted with 1 R d ;

R d is independently selected from: F, Cl, Br, I, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, OC 1-6 alkyl, NO 2 , —CN, CF 3 , and OCF 3 ;

R 1 and R 2 are independently selected from: H, C 1-8 alkyl, C 3-8 alkenyl, C 3-8 alkynyl, C 1-8 alkoxy, C 3-8 cycloalkyl, (C 3-8 cycloalkyl)C 1-8 alkylene, C 4-10 heterocycle, (C 4-10 heterocycle)C 1-8 alkylene, C 6-10 aryl, (C 6-10 aryl)C 1-8 alkylene, C 5-10 heteroaryl, and (C 5-10 heteroaryl)C 1-8 alkylene, wherein R 1 and R 2 are independently optionally substituted with 1-2 R 1a ;

R 1a is independently selected from: F, Cl, Br, I, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, —(CH 2 ) a OR a , —(CH 2 ) a NR a R a , —(CH 2 ) a NHOH, —(CH 2 ) a NR a NR a R a , —(CH 2 ) n NO 2 , —(CH 2 ) a CN, —(CH 2 ) a CO 2 R a , —(CH 2 ) a C(O)R a , —(CH 2 ) a OC(O)R a , —(CH 2 ) a CONR a R a , CF 3 , and OCF 3 ;

R a is independently selected from: H, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-8 cycloalkyl, (C 3-8 cycloalkyl)C 1-8 alkylene, C 4-10 heterocycle, (C 4-10 heterocycle)C 1-8 alkylene, C 6-10 aryl, (C 6-10 aryl)C 1-8 alkylene, C 5-10 heteroaryl, and (C 5-10 heteroaryl)C 1-8 alkylene, wherein the alkyl is optionally interrupted with 1-2 heteroatoms selected from the group consisting of —O—, —S(O) p — and —NR b —;

R b is independently selected from the group consisting of H, C 1-6 alkyl, and benzyl;

R 3 is selected from: OH, C 1-8 alkoxy, NR 3a R 3b , C 3-8 cycloalkyl, C 4-10 heterocycle, C 6-10 aryl, and C 5-10 heteroaryl, wherein the cycloalkyl, heterocycle, aryl, and heteroaryl are optionally substituted with 1-2 R 3c ;

R 3a and R 3b are independently selected from: C 1-8 alkyl, C 2-8 alkenyl, C 2-8 alkynyl, phenyl, and benzyl;

R 3c is independently selected from: F, Cl, Br, I, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, —(CH 2 ) a OR a , —(CH 2 ) a NR a R a , —(CH 2 ) a NHOH, —(CH 2 ) a NR a NR a R a , —(CH 2 ) a NO 2 , —(CH 2 ) a CN, —(CH 2 ) a CO 2 R a , —(CH 2 ) a C(O)R a , —(CH 2 ) a OC(O)R a , —(CH 2 ) a CONR a R a , CF 3 , and OCF 3 ;

X is selected from: (CH 2 ) q , (CH 2 ) r C(O), and (CH 2 ) r C(O)NR 4 ;

R 4 is selected from: H, C 1-4 alkyl, C 1-4 alkoxy, and C 1-4 haloalkyl;

Y is selected from: 5-10 membered heteroaryl and 6-10 membered aryl, wherein Y is optionally substituted with 1-4 Y 1 ;

Y 1 is independently selected from: F, Cl, Br, I, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, —(CH 2 ) a OR a , —(CH 2 ) a NR a R a , —(CH 2 ) a NHOH, —(CH 2 ) a NR a NR a R a , —(CH 2 ) a NO 2 , —(CH 2 ) a CN, —(CH 2 ) a CO 2 R a , —(CH 2 ) a C(O)R a , —(CH 2 ) a OC(O)R a , —(CH 2 ) a CONR a R a , CF 3 , and OCF 3 ;

a is independently selected from the group consisting of 0, 1, and 2;

n is independently selected from: 1, 2, and 3;

p is independently selected from: 0, 1, and 2;

q is independently selected from 1, 2, 3, and 4; and,

r is independently selected from 0, 1, 2, and 3.

11. The method according to claim 10 , wherein the compound is of formula II or a stereoisomer or a pharmaceutically acceptable salt thereof:

wherein:

R is selected from: H and C 1-4 alkyl;

R 1 and R 2 are independently selected from: H, C 1-4 alkyl, C 3-4 alkenyl, C 3-4 alkynyl, C 3-6 cycloalkyl, (C 3-6 cycloalkyl)C 1-2 alkylene, C 5-6 heterocycle, (C 5-6 heterocycle)C 1-2 alkylene, C 6-10 aryl, (C 6-10 aryl)C 1-2 alkylene, C 5-10 heteroaryl, and (C 5-10 heteroaryl)C 1-2 alkylene, wherein R 1 and R 2 are independently optionally substituted with 1-2 R 1a ;

R 1a is independently selected from: F, Cl, Br, I, C 1-4 alkyl, OR a , NR a R a , NO 2 , —CN, CO 2 R a , C(O)R a , OC(O)R a , CONR a R a , CF 3 , and OCF 3 ;

R 3 is selected from: OCH 3 , OCH 2 CH 3 , NR 3a R 3b , C 3-6 cycloalkyl, and C 5-6 heterocycle, wherein the cycloalkyl and heterocycle are optionally substituted with 1-2 R 3c ;

R 3a and R 3b are independently selected from: C 1-4 alkyl, phenyl, and benzyl;

R 3c is independently selected from: F, Cl, Br, I, C 1-4 alkyl, OR a , NR a R a , NO 2 , —CN, CO 2 R a , C(O)R a , OC(O)R a , CONR a R a , CF 3 , and OCF 3 ;

Y is selected from: 5-6 membered heteroaryl and phenyl, wherein Y is optionally substituted with 1-2 Y 1 ;

Y 1 is independently selected from: F, Cl, Br, I, C 1-4 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, OR a , NR a R a , NO 2 , —CN, CO 2 R a , C(O)R a , OC(O)R a , CONR a R a , CF 3 , and OCF 3 ; and,

R a is independently selected from: H, C 1-4 alkyl, C 3-6 cycloalkyl, phenyl, and benzyl.

12. The method according to claim 11 , wherein:

R is H;

R 1 and R 2 are independently selected from: n-propyl, cyclopropylmethyl, and cyclobutyl;

R 3 is selected from: cyclopropyl, cyclobutyl, N-pyrrolidino, N-piperidino, N-piperazino, and N-morpholino;

Y is selected from: pyridyl and pyrimidyl, wherein Y is optionally substituted with 1-2 Y 1 ; and,

Y 1 is independently selected from: F, Cl, CH 3 , OCH 3 , NO 2 , —CN, and CF 3 .

13. The method according to claim 12 , wherein:

R 1 is selected from: n-propyl and cyclopropylmethyl; and,

R 2 is n-propyl.

14. The method according to claim 12 , wherein:

R 1 is n-propyl; and,

R 2 is n-propyl.

15. The method according to claim 10 , wherein the compound is of formula IV or a stereoisomer or a pharmaceutically acceptable salt thereof:

wherein:

R is selected from: H and C 1-4 alkyl;

R 1 and R 2 are independently selected from: H, C 1-4 alkyl, C 3-4 alkenyl, C 3-4 alkynyl, C 3-6 cycloalkyl, (C 3-6 cycloalkyl)C 1-2 alkylene, C 5-6 heterocycle, (C 5-6 heterocycle)C 1-2 alkylene, C 6-10 aryl, (C 6-10 aryl)C 1-2 alkylene, C 5-10 heteroaryl, and (C 5-10 heteroaryl)C 1-2 alkylene, wherein R 1 and R 2 are independently optionally substituted with 1-2 R 1a ;

R 1a is independently selected from: F, Cl, Br, I, C 1-4 alkyl, OR a , NR a R a , NO 2 , —CN, CO 2 R a , C(O)R a , OC(O)R a , CONR a R a , CF 3 , and OCF 3 ;

R 3 is selected from: OCH 3 , OCH 2 CH 3 , NR 3a R 3b , C 3-6 cycloalkyl, and C 5-6 heterocycle, wherein the cycloalkyl and heterocycle are optionally substituted with 1-2 R 3c ;

R 3a and R 3b are independently selected from: C 1-4 alkyl, phenyl, and benzyl;

R 3c is independently selected from: F, Cl, Br, I, C 1-4 alkyl, OR a , NR a R a , NO 2 , —CN, CO 2 R a , C(O)R a , OC(O)R a , CONR a R a , CF 3 , and OCF 3 ;

Y is selected from: 5-6 membered heteroaryl and phenyl, wherein Y is optionally substituted with 1-2 Y 1 ;

Y 1 is independently selected from: F, Cl, Br, I, C 1-4 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, OR a , NR a R a , NO 2 , —CN, CO 2 R a , C(O)R a , OC(O)R a , CONR a R a , CF 3 , and OCF 3 ; and,

R a is independently selected from: H, C 1-4 alkyl, C 3-6 cycloalkyl, phenyl, and benzyl.

16. The method according to claim 10 , wherein the compound is of formula V or VI or stereoisomer or a pharmaceutically acceptable salt thereof:

17. The method according to claim 10 , wherein the compound is:

or a pharmaceutically acceptable salt thereof.

18. The method according to claim 10 , wherein the compound is selected from

wherein R, R 1 , R 2 , R 3 and Y′ are as defined in the following table:

Ex.#

R

R 1

R 2

R 3

Y′

1

H

n-propyl

n-propyl

CH 2 OCH 3

H

2

H

n-propyl

n-propyl

CH 3

H

3

H

n-propyl

n-propyl

CH 2 OH

H

4

H

n-propyl

n-propyl

CH 2 N(CH 3 ) 2

H

5

H

n-propyl

n-propyl

CH 2 -N-piperdinyl

H

6

H

n-propyl

n-propyl

CH 2 -N-morpholinyl

H

7

H

n-propyl

n-propyl

cyclopropyl

H

8

H

n-propyl

n-propyl

CH 2 -cyclopropyl

H

9

H

n-propyl

n-propyl

2-tetrahydrofuranyl

H

10

H

n-propyl

n-propyl

CH 2 -2-tetrahydrofuran

H

11

H

n-propyl

n-propyl

2-tetrahydrothienyl

H

12

H

n-propyl

n-propyl

CH 2 OCH 3

CF 3

13

H

n-propyl

n-propyl

CH 3

CF 3

14

H

n-propyl

n-propyl

CH 2 OH

CF 3

15

H

n-propyl

n-propyl

CH 2 N(CH 3 ) 2

CF 3

16

H

n-propyl

n-propyl

CH 2 -N-piperdinyl

CF 3

17

H

n-propyl

n-propyl

CH 2 -N-morpholinyl

CF 3

18

H

n-propyl

n-propyl

cyclopropyl

CF 3

19

H

n-propyl

n-propyl

CH 2 -cyclopropyl

CF 3

20

H

n-propyl

n-propyl

2-tetrahydrofuranyl

CF 3

21

H

n-propyl

n-propyl

CH 2 -2-tetrahydrofuran

CF 3

22

H

n-propyl

n-propyl

2-tetrahydrothienyl

CF 3

23

H

n-propyl

n-propyl

CH 2 OCH 3

F

24

H

n-propyl

n-propyl

CH 3

F

25

H

n-propyl

n-propyl

CH 2 OH

F

26

H

n-propyl

n-propyl

CH 2 N(CH 3 ) 2

F

27

H

n-propyl

n-propyl

CH 2 -N-piperdinyl

F

28

H

n-propyl

n-propyl

CH 2 -N-morpholinyl

F

29

H

n-propyl

n-propyl

cyclopropyl

F

30

H

n-propyl

n-propyl

CH 2 -cyclopropyl

F

31

H

n-propyl

n-propyl

2-tetrahydrofuranyl

F

32

H

n-propyl

n-propyl

CH 2 -2-tetrahydrofuran

F

33

H

n-propyl

n-propyl

2-tetrahydrothienyl

F

34

H

n-propyl

n-propyl

CH 2 OCH 3

Cl

35

H

n-propyl

n-propyl

CH 3

Cl

36

H

n-propyl

n-propyl

CH 2 OH

Cl

37

H

n-propyl

n-propyl

CH 2 N(CH 3 ) 2

Cl

38

H

n-propyl

n-propyl

CH 2 -N-piperdinyl

Cl

39

H

n-propyl

n-propyl

CH 2 -N-morpholinyl

Cl

40

H

n-propyl

n-propyl

cyclopropyl

Cl

41

H

n-propyl

n-propyl

CH 2 -cyclopropyl

Cl

42

H

n-propyl

n-propyl

2-tetrahydrofuranyl

Cl

43

H

n-propyl

n-propyl

CH 2 -2-tetrahydrofuran

Cl

44

H

n-propyl

n-propyl

2-tetrahydrothienyl

Cl

45

H

n-propyl

n-propyl

CH 2 OCH 3

Br

46

H

n-propyl

n-propyl

CH 3

Br

47

H

n-propyl

n-propyl

CH 2 OH

Br

48

H

n-propyl

n-propyl

CH 2 N(CH 3 ) 2

Br

49

H

n-propyl

n-propyl

CH 2 -N-piperdinyl

Br

50

H

n-propyl

n-propyl

CH 2 -N-morpholinyl

Br

51

H

n-propyl

n-propyl

cyclopropyl

Br

52

H

n-propyl

n-propyl

CH 2 -cyclopropyl

Br

53

H

n-propyl

n-propyl

2-tetrahydrofuranyl

Br

54

H

n-propyl

n-propyl

CH 2 -2-tetrahydrofuran

Br

55

H

n-propyl

n-propyl

2-tetrahydrothienyl

Br

56

H

n-propyl

n-propyl

CH 2 OCH 3

I

57

H

n-propyl

n-propyl

CH 3

I

58

H

n-propyl

n-propyl

CH 2 OH

I

59

H

n-propyl

n-propyl

CH 2 N(CH 3 ) 2

I

60

H

n-propyl

n-propyl

CH 2 -N-piperdinyl

I

61

H

n-propyl

n-propyl

CH 2 -N-morpholinyl

I

62

H

n-propyl

n-propyl

cyclopropyl

I

63

H

n-propyl

n-propyl

CH 2 -cyclopropyl

I

64

H

n-propyl

n-propyl

2-tetrahydrofuranyl

I

65

H

n-propyl

n-propyl

CH 2 -2-tetrahydrofuran

I

66

H

n-propyl

n-propyl

2-tetrahydrothienyl

I

67

H

i-propyl

n-propyl

CH 2 OCH 3

H

68

H

i-propyl

n-propyl

CH 3

H

69

H

i-propyl

n-propyl

CH 2 OH

H

70

H

i-propyl

n-propyl

CH 2 N(CH 3 ) 2

H

71

H

i-propyl

n-propyl

CH 2 -N-piperdinyl

H

72

H

i-propyl

n-propyl

CH 2 -N-morpholinyl

H

73

H

i-propyl

n-propyl

cyclopropyl

H

74

H

i-propyl

n-propyl

CH 2 -cyclopropyl

H

75

H

i-propyl

n-propyl

2-tetrahydrofuranyl

H

76

H

i-propyl

n-propyl

CH 2 -2-tetrahydrofuran

H

77

H

i-propyl

n-propyl

2-tetrahydrothienyl

H

78

H

i-propyl

n-propyl

CH 2 OCH 3

CF 3

79

H

i-propyl

n-propyl

CH 3

CF 3

80

H

i-propyl

n-propyl

CH 2 OH

CF 3

81

H

i-propyl

n-propyl

CH 2 N(CH 3 ) 2

CF 3

82

H

i-propyl

n-propyl

CH 2 -N-piperdinyl

CF 3

83

H

i-propyl

n-propyl

CH 2 -N-morpholinyl

CF 3

84

H

i-propyl

n-propyl

cyclopropyl

CF 3

85

H

i-propyl

n-propyl

CH 2 -cyclopropyl

CF 3

86

H

i-propyl

n-propyl

2-tetrahydrofuranyl

CF 3

87

H

i-propyl

n-propyl

CH 2 -2-tetrahydrofuran

CF 3

88

H

i-propyl

n-propyl

2-tetrahydrothienyl

CF 3

89

H

i-propyl

n-propyl

CH 2 OCH 3

F

90

H

i-propyl

n-propyl

CH 3

F

91

H

i-propyl

n-propyl

CH 2 OH

F

92

H

i-propyl

n-propyl

CH 2 N(CH 3 ) 2

F

93

H

i-propyl

n-propyl

CH 2 -N-piperdinyl

F

94

H

i-propyl

n-propyl

CH 2 -N-morpholinyl

F

95

H

i-propyl

n-propyl

cyclopropyl

F

96

H

i-propyl

n-propyl

CH 2 -cyclopropyl

F

97

H

i-propyl

n-propyl

2-tetrahydrofuranyl

F

98

H

i-propyl

n-propyl

CH 2 -2-tetrahydrofuran

F

99

H

i-propyl

n-propyl

2-tetrahydrothienyl

F

100

H

i-propyl

n-propyl

CH 2 OCH 3

Cl

101

H

i-propyl

n-propyl

CH 3

Cl

102

H

i-propyl

n-propyl

CH 2 OH

Cl

103

H

i-propyl

n-propyl

CH 2 N(CH 3 ) 2

Cl

104

H

i-propyl

n-propyl

CH 2 -N-piperdinyl

Cl

105

H

i-propyl

n-propyl

CH 2 -N-morpholinyl

Cl

106

H

i-propyl

n-propyl

cyclopropyl

Cl

107

H

i-propyl

n-propyl

CH 2 -cyclopropyl

Cl

108

H

i-propyl

n-propyl

2-tetrahydrofuranyl

Cl

109

H

i-propyl

n-propyl

CH 2 -2-tetrahydrofuran

Cl

110

H

i-propyl

n-propyl

2-tetrahydrothienyl

Cl

111

H

i-propyl

n-propyl

CH 2 OCH 3

Br

112

H

i-propyl

n-propyl

CH 3

Br

113

H

i-propyl

n-propyl

CH 2 OH

Br

114

H

i-propyl

n-propyl

CH 2 N(CH 3 ) 2

Br

115

H

i-propyl

n-propyl

CH 2 -N-piperdinyl

Br

116

H

i-propyl

n-propyl

CH 2 -N-morpholinyl

Br

117

H

i-propyl

n-propyl

cyclopropyl

Br

118

H

i-propyl

n-propyl

CH 2 -cyclopropyl

Br

119

H

i-propyl

n-propyl

2-tetrahydrofuranyl

Br

120

H

i-propyl

n-propyl

CH 2 -2-tetrahydrofuran

Br

121

H

i-propyl

n-propyl

2-tetrahydrothienyl

Br

122

H

i-propyl

n-propyl

CH 2 OCH 3

I

123

H

i-propyl

n-propyl

CH 3

I

124

H

i-propyl

n-propyl

CH 2 OH

I

125

H

i-propyl

n-propyl

CH 2 N(CH 3 ) 2

I

126

H

i-propyl

n-propyl

CH 2 -N-piperdinyl

I

127

H

i-propyl

n-propyl

CH 2 -N-morpholinyl

I

128

H

i-propyl

n-propyl

cyclopropyl

I

129

H

i-propyl

n-propyl

CH 2 -cyclopropyl

I

130

H

i-propyl

n-propyl

2-tetrahydrofuranyl

I

131

H

i-propyl

n-propyl

CH 2 -2-tetrahydrofuran

I

132

H

i-propyl

n-propyl

2-tetrahydrothienyl

I

133

H

n-butyl

n-propyl

CH 2 OCH 3

H

134

H

n-butyl

n-propyl

CH 3

H

135

H

n-butyl

n-propyl

CH 2 OH

H

136

H

n-butyl

n-propyl

CH 2 N(CH 3 ) 2

H

137

H

n-butyl

n-propyl

CH 2 -N-piperdinyl

H

138

H

n-butyl

n-propyl

CH 2 -N-morpholinyl

H

139

H

n-butyl

n-propyl

cyclopropyl

H

140

H

n-butyl

n-propyl

CH 2 -cyclopropyl

H

141

H

n-butyl

n-propyl

2-tetrahydrofuranyl

H

142

H

n-butyl

n-propyl

CH 2 -2-tetrahydrofuran

H

143

H

n-butyl

n-propyl

2-tetrahydrothienyl

H

144

H

n-butyl

n-propyl

CH 2 OCH 3

CF 3

145

H

n-butyl

n-propyl

CH 3

CF 3

146

H

n-butyl

n-propyl

CH 2 OH

CF 3

147

H

n-butyl

n-propyl

CH 2 N(CH 3 ) 2

CF 3

148

H

n-butyl

n-propyl

CH 2 -N-piperdinyl

CF 3

149

H

n-butyl

n-propyl

CH 2 -N-morpholinyl

CF 3

150

H

n-butyl

n-propyl

cyclopropyl

CF 3

151

H

n-butyl

n-propyl

CH 2 -cyclopropyl

CF 3

152

H

n-butyl

n-propyl

2-tetrahydrofuranyl

CF 3

153

H

n-butyl

n-propyl

CH 2 -2-tetrahydrofuran

CF 3

154

H

n-butyl

n-propyl

2-tetrahydrothienyl

CF 3

155

H

n-butyl

n-propyl

CH 2 OCH 3

F

156

H

n-butyl

n-propyl

CH 3

F

157

H

n-butyl

n-propyl

CH 2 OH

F

158

H

n-butyl

n-propyl

CH 2 N(CH 3 ) 2

F

159

H

n-butyl

n-propyl

CH 2 -N-piperdinyl

F

160

H

n-butyl

n-propyl

CH 2 -N-morpholinyl

F

161

H

n-butyl

n-propyl

cyclopropyl

F

162

H

n-butyl

n-propyl

CH 2 -cyclopropyl

F

163

H

n-butyl

n-propyl

2-tetrahydrofuranyl

F

164

H

n-butyl

n-propyl

CH 2 -2-tetrahydrofuran

F

165

H

n-butyl

n-propyl

2-tetrahydrothienyl

F

166

H

n-butyl

n-propyl

CH 2 OCH 3

Cl

167

H

n-butyl

n-propyl

CH 3

Cl

168

H

n-butyl

n-propyl

CH 2 OH

Cl

169

H

n-butyl

n-propyl

CH 2 N(CH 3 ) 2

Cl

170

H

n-butyl

n-propyl

CH 2 -N-piperdinyl

Cl

171

H

n-butyl

n-propyl

CH 2 -N-morpholinyl

Cl

172

H

n-butyl

n-propyl

cyclopropyl

Cl

173

H

n-butyl

n-propyl

CH 2 -cyclopropyl

Cl

174

H

n-butyl

n-propyl

2-tetrahydrofuranyl

Cl

175

H

n-butyl

n-propyl

CH 2 -2-tetrahydrofuran

Cl

176

H

n-butyl

n-propyl

2-tetrahydrothienyl

Cl

177

H

n-butyl

n-propyl

CH 2 OCH 3

Br

178

H

n-butyl

n-propyl

CH 3

Br

179

H

n-butyl

n-propyl

CH 2 OH

Br

180

H

n-butyl

n-propyl

CH 2 N(CH 3 ) 2

Br

181

H

n-butyl

n-propyl

CH 2 -N-piperdinyl

Br

182

H

n-butyl

n-propyl

CH 2 -N-morpholinyl

Br

183

H

n-butyl

n-propyl

cyclopropyl

Br

184

H

n-butyl

n-propyl

CH 2 -cyclopropyl

Br

185

H

n-butyl

n-propyl

2-tetrahydrofuranyl

Br

186

H

n-butyl

n-propyl

CH 2 -2-tetrahydrofuran

Br

187

H

n-butyl

n-propyl

2-tetrahydrothienyl

Br

188

H

n-butyl

n-propyl

CH 2 OCH 3

I

189

H

n-butyl

n-propyl

CH 3

I

190

H

n-butyl

n-propyl

CH 2 OH

I

191

H

n-butyl

n-propyl

CH 2 N(CH 3 ) 2

I

192

H

n-butyl

n-propyl

CH 2 -N-piperdinyl

I

193

H

n-butyl

n-propyl

CH 2 -N-morpholinyl

I

194

H

n-butyl

n-propyl

cyclopropyl

I

195

H

n-butyl

n-propyl

CH 2 -cyclopropyl

I

196

H

n-butyl

n-propyl

2-tetrahydrofuranyl

I

197

H

n-butyl

n-propyl

CH 2 -2-tetrahydrofuran

I

198

H

n-butyl

n-propyl

2-tetrahydrothienyl

I

199

H

i-butyl

n-propyl

CH 2 OCH 3

H

200

H

i-butyl

n-propyl

CH 3

H

201

H

i-butyl

n-propyl

CH 2 OH

H

202

H

i-butyl

n-propyl

CH 2 N(CH 3 ) 2

H

203

H

i-butyl

n-propyl

CH 2 -N-piperdinyl

H

204

H

i-butyl

n-propyl

CH 2 -N-morpholinyl

H

205

H

i-butyl

n-propyl

cyclopropyl

H

206

H

i-butyl

n-propyl

CH 2 -cyclopropyl

H

207

H

i-butyl

n-propyl

2-tetrahydrofuranyl

H

208

H

i-butyl

n-propyl

CH 2 -2-tetrahydrofuran

H

209

H

i-butyl

n-propyl

2-tetrahydrothienyl

H

210

H

i-butyl

n-propyl

CH 2 OCH 3

CF 3

211

H

i-butyl

n-propyl

CH 3

CF 3

212

H

i-butyl

n-propyl

CH 2 OH

CF 3

213

H

i-butyl

n-propyl

CH 2 N(CH 3 ) 2

CF 3

214

H

i-butyl

n-propyl

CH 2 -N-piperdinyl

CF 3

215

H

i-butyl

n-propyl

CH 2 -N-morpholinyl

CF 3

216

H

i-butyl

n-propyl

cyclopropyl

CF 3

217

H

i-butyl

n-propyl

CH 2 -cyclopropyl

CF 3

218

H

i-butyl

n-propyl

2-tetrahydrofuranyl

CF 3

219

H

i-butyl

n-propyl

CH 2 -2-tetrahydrofuran

CF 3

220

H

i-butyl

n-propyl

2-tetrahydrothienyl

CF 3

221

H

i-butyl

n-propyl

CH 2 OCH 3

F

222

H

i-butyl

n-propyl

CH 3

F

223

H

i-butyl

n-propyl

CH 2 OH

F

224

H

i-butyl

n-propyl

CH 2 N(CH 3 ) 2

F

225

H

i-butyl

n-propyl

CH 2 -N-piperdinyl

F

226

H

i-butyl

n-propyl

CH 2 -N-morpholinyl

F

227

H

i-butyl

n-propyl

cyclopropyl

F

228

H

i-butyl

n-propyl

CH 2 -cyclopropyl

F

229

H

i-butyl

n-propyl

2-tetrahydrofuranyl

F

230

H

i-butyl

n-propyl

CH 2 -2-tetrahydrofuran

F

231

H

i-butyl

n-propyl

2-tetrahydrothienyl

F

232

H

i-butyl

n-propyl

CH 2 OCH 3

Cl

233

H

i-butyl

n-propyl

CH 3

Cl

234

H

i-butyl

n-propyl

CH 2 OH

Cl

235

H

i-butyl

n-propyl

CH 2 N(CH 3 ) 2

Cl

236

H

i-butyl

n-propyl

CH 2 -N-piperdinyl

Cl

237

H

i-butyl

n-propyl

CH 2 -N-morpholinyl

Cl

238

H

i-butyl

n-propyl

cyclopropyl

Cl

239

H

i-butyl

n-propyl

CH 2 -cyclopropyl

Cl

240

H

i-butyl

n-propyl

2-tetrahydrofuranyl

Cl

241

H

i-butyl

n-propyl

CH 2 -2-tetrahydrofuran

Cl

242

H

i-butyl

n-propyl

2-tetrahydrothienyl

Cl

243

H

i-butyl

n-propyl

CH 2 OCH 3

Br

244

H

i-butyl

n-propyl

CH 3

Br

245

H

i-butyl

n-propyl

CH 2 OH

Br

246

H

i-butyl

n-propyl

CH 2 N(CH 3 ) 2

Br

247

H

i-butyl

n-propyl

CH 2 -N-piperdinyl

Br

248

H

i-butyl

n-propyl

CH 2 -N-morpholinyl

Br

249

H

i-butyl

n-propyl

cyclopropyl

Br

250

H

i-butyl

n-propyl

CH 2 -cyclopropyl

Br

251

H

i-butyl

n-propyl

2-tetrahydrofuranyl

Br

252

H

i-butyl

n-propyl

CH 2 -2-tetrahydrofuran

Br

253

H

i-butyl

n-propyl

2-tetrahydrothienyl

Br

254

H

i-butyl

n-propyl

CH 2 OCH 3

I

255

H

i-butyl

n-propyl

CH 3

I

256

H

i-butyl

n-propyl

CH 2 OH

I

257

H

i-butyl

n-propyl

CH 2 N(CH 3 ) 2

I

258

H

i-butyl

n-propyl

CH 2 -N-piperdinyl

I

259

H

i-butyl

n-propyl

CH 2 -N-morpholinyl

I

260

H

i-butyl

n-propyl

cyclopropyl

I

261

H

i-butyl

n-propyl

CH 2 -cyclopropyl

I

262

H

i-butyl

n-propyl

2-tetrahydrofuranyl

I

263

H

i-butyl

n-propyl

CH 2 -2-tetrahydrofuran

I

264

H

i-butyl

n-propyl

2-tetrahydrothienyl

I

265

H

cyclobutyl

n-propyl

CH 2 OCH 3

H

266

H

cyclobutyl

n-propyl

CH 3

H

267

H

cyclobutyl

n-propyl

CH 2 OH

H

268

H

cyclobutyl

n-propyl

CH 2 N(CH 3 ) 2

H

269

H

cyclobutyl

n-propyl

CH 2 -N-piperdinyl

H

270

H

cyclobutyl

n-propyl

CH 2 -N-morpholinyl

H

271

H

cyclobutyl

n-propyl

cyclopropyl

H

272

H

cyclobutyl

n-propyl

CH 2 -cyclopropyl

H

273

H

cyclobutyl

n-propyl

2-tetrahydrofuranyl

H

274

H

cyclobutyl

n-propyl

CH 2 -2-tetrahydrofuran

H

275

H

cyclobutyl

n-propyl

2-tetrahydrothienyl

H

276

H

cyclobutyl

n-propyl

CH 2 OCH 3

CF 3

277

H

cyclobutyl

n-propyl

CH 3

CF 3

278

H

cyclobutyl

n-propyl

CH 2 OH

CF 3

279

H

cyclobutyl

n-propyl

CH 2 N(CH 3 ) 2

CF 3

280

H

cyclobutyl

n-propyl

CH 2 -N-piperdinyl

CF 3

281

H

cyclobutyl

n-propyl

CH 2 -N-morpholinyl

CF 3

282

H

cyclobutyl

n-propyl

cyclopropyl

CF 3

283

H

cyclobutyl

n-propyl

CH 2 -cyclopropyl

CF 3

284

H

cyclobutyl

n-propyl

2-tetrahydrofuranyl

CF 3

285

H

cyclobutyl

n-propyl

CH 2 -2-tetrahydrofuran

CF 3

286

H

cyclobutyl

n-propyl

2-tetrahydrothienyl

CF 3

287

H

cyclobutyl

n-propyl

CH 2 OCH 3

F

288

H

cyclobutyl

n-propyl

CH 3

F

289

H

cyclobutyl

n-propyl

CH 2 OH

F

290

H

cyclobutyl

n-propyl

CH 2 N(CH 3 ) 2

F

291

H

cyclobutyl

n-propyl

CH 2 -N-piperdinyl

F

292

H

cyclobutyl

n-propyl

CH 2 -N-morpholinyl

F

293

H

cyclobutyl

n-propyl

cyclopropyl

F

294

H

cyclobutyl

n-propyl

CH 2 -cyclopropyl

F

295

H

cyclobutyl

n-propyl

2-tetrahydrofuranyl

F

296

H

cyclobutyl

n-propyl

CH 2 -2-tetrahydrofuran

F

297

H

cyclobutyl

n-propyl

2-tetrahydrothienyl

F

298

H

cyclobutyl

n-propyl

CH 2 OCH 3

Cl

299

H

cyclobutyl

n-propyl

CH 3

Cl

300

H

cyclobutyl

n-propyl

CH 2 OH

Cl

301

H

cyclobutyl

n-propyl

CH 2 N(CH 3 ) 2

Cl

302

H

cyclobutyl

n-propyl

CH 2 -N-piperdinyl

Cl

303

H

cyclobutyl

n-propyl

CH 2 -N-morpholinyl

Cl

304

H

cyclobutyl

n-propyl

cyclopropyl

Cl

305

H

cyclobutyl

n-propyl

CH 2 -cyclopropyl

Cl

306

H

cyclobutyl

n-propyl

2-tetrahydrofuranyl

Cl

307

H

cyclobutyl

n-propyl

CH 2 -2-tetrahydrofuran

Cl

308

H

cyclobutyl

n-propyl

2-tetrahydrothienyl

Cl

309

H

cyclobutyl

n-propyl

CH 2 OCH 3

Br

310

H

cyclobutyl

n-propyl

CH 3

Br

311

H

cyclobutyl

n-propyl

CH 2 OH

Br

312

H

cyclobutyl

n-propyl

CH 2 N(CH 3 ) 2

Br

313

H

cyclobutyl

n-propyl

CH 2 -N-piperdinyl

Br

314

H

cyclobutyl

n-propyl

CH 2 -N-morpholinyl

Br

315

H

cyclobutyl

n-propyl

cyclopropyl

Br

316

H

cyclobutyl

n-propyl

CH 2 -cyclopropyl

Br

317

H

cyclobutyl

n-propyl

2-tetrahydrofuranyl

Br

318

H

cyclobutyl

n-propyl

CH 2 -2-tetrahydrofuran

Br

319

H

cyclobutyl

n-propyl

2-tetrahydrothienyl

Br

320

H

cyclobutyl

n-propyl

CH 2 OCH 3

I

321

H

cyclobutyl

n-propyl

CH 3

I

322

H

cyclobutyl

n-propyl

CH 2 OH

I

323

H

cyclobutyl

n-propyl

CH 2 N(CH 3 ) 2

I

324

H

cyclobutyl

n-propyl

CH 2 -N-piperdinyl

I

325

H

cyclobutyl

n-propyl

CH 2 -N-morpholinyl

I

326

H

cyclobutyl

n-propyl

cyclopropyl

I

327

H

cyclobutyl

n-propyl

CH 2 -cyclopropyl

I

328

H

cyclobutyl

n-propyl

2-tetrahydrofuranyl

I

329

H

cyclobutyl

n-propyl

CH 2 -2-tetrahydrofuran

I

330

H

cyclobutyl

n-propyl

2-tetrahydrothienyl

I

331

H

cyclopropylmethyl-

n-propyl

CH 2 OCH 3

H

332

H

cyclopropylmethyl-

n-propyl

CH 3

H

333

H

cyclopropylmethyl-

n-propyl

CH 2 OH

H

334

H

cyclopropylmethyl-

n-propyl

CH 2 N(CH 3 ) 2

H

335

H

cyclopropylmethyl-

n-propyl

CH 2 -N-piperdinyl

H

336

H

cyclopropylmethyl-

n-propyl

CH 2 -N-morpholinyl

H

337

H

cyclopropylmethyl-

n-propyl

cyclopropyl

H

338

H

cyclopropylmethyl-

n-propyl

CH 2 -cyclopropyl

H

339

H

cyclopropylmethyl-

n-propyl

2-tetrahydrofuranyl

H

340

H

cyclopropylmethyl-

n-propyl

CH 2 -2-tetrahydrofuran

H

341

H

cyclopropylmethyl-

n-propyl

2-tetrahydrothienyl

H

342

H

cyclopropylmethyl-

n-propyl

CH 2 OCH 3

CF 3

343

H

cyclopropylmethyl-

n-propyl

CH 3

CF 3

344

H

cyclopropylmethyl-

n-propyl

CH 2 OH

CF 3

345

H

cyclopropylmethyl-

n-propyl

CH 2 N(CH 3 ) 2

CF 3

346

H

cyclopropylmethyl-

n-propyl

CH 2 -N-piperdinyl

CF 3

347

H

cyclopropylmethyl-

n-propyl

CH 2 -N-morpholinyl

CF 3

348

H

cyclopropylmethyl-

n-propyl

cyclopropyl

CF 3

349

H

cyclopropylmethyl-

n-propyl

CH 2 -cyclopropyl

CF 3

350

H

cyclopropylmethyl-

n-propyl

2-tetrahydrofuranyl

CF 3

351

H

cyclopropylmethyl-

n-propyl

CH 2 -2-tetrahydrofuran

CF 3

352

H

cyclopropylmethyl-

n-propyl

2-tetrahydrothienyl

CF 3

353

H

cyclopropylmethyl-

n-propyl

CH 2 OCH 3

F

354

H

cyclopropylmethyl-

n-propyl

CH 3

F

355

H

cyclopropylmethyl-

n-propyl

CH 2 OH

F

356

H

cyclopropylmethyl-

n-propyl

CH 2 N(CH 3 ) 2

F

357

H

cyclopropylmethyl-

n-propyl

CH 2 -N-piperdinyl

F

358

H

cyclopropylmethyl-

n-propyl

CH 2 -N-morpholinyl

F

359

H

cyclopropylmethyl-

n-propyl

cyclopropyl

F

360

H

cyclopropylmethyl-

n-propyl

CH 2 -cyclopropyl

F

361

H

cyclopropylmethyl-

n-propyl

2-tetrahydrofuranyl

F

362

H

cyclopropylmethyl-

n-propyl

CH 2 -2-tetrahydrofuran

F

363

H

cyclopropylmethyl-

n-propyl

2-tetrahydrothienyl

F

364

H

cyclopropylmethyl-

n-propyl

CH 2 OCH 3

Cl

365

H

cyclopropylmethyl-

n-propyl

CH 3

Cl

366

H

cyclopropylmethyl-

n-propyl

CH 2 OH

Cl

367

H

cyclopropylmethyl-

n-propyl

CH 2 N(CH 3 ) 2

Cl

368

H

cyclopropylmethyl-

n-propyl

CH 2 -N-piperdinyl

Cl

369

H

cyclopropylmethyl-

n-propyl

CH 2 -N-morpholinyl

Cl

370

H

cyclopropylmethyl-

n-propyl

cyclopropyl

Cl

371

H

cyclopropylmethyl-

n-propyl

CH 2 -cyclopropyl

Cl

372

H

cyclopropylmethyl-

n-propyl

2-tetrahydrofuranyl

Cl

373

H

cyclopropylmethyl-

n-propyl

CH 2 -2-tetrahydrofuran

Cl

374

H

cyclopropylmethyl-

n-propyl

2-tetrahydrothienyl

Cl

375

H

cyclopropylmethyl-

n-propyl

CH 2 OCH 3

Br

376

H

cyclopropylmethyl-

n-propyl

CH 3

Br

377

H

cyclopropylmethyl-

n-propyl

CH 2 OH

Br

378

H

cyclopropylmethyl-

n-propyl

CH 2 N(CH 3 ) 2

Br

379

H

cyclopropylmethyl-

n-propyl

CH 2 -N-piperdinyl

Br

380

H

cyclopropylmethyl-

n-propyl

CH 2 -N-morpholinyl

Br

381

H

cyclopropylmethyl-

n-propyl

cyclopropyl

Br

382

H

cyclopropylmethyl-

n-propyl

CH 2 -cyclopropyl

Br

383

H

cyclopropylmethyl-

n-propyl

2-tetrahydrofuranyl

Br

384

H

cyclopropylmethyl-

n-propyl

CH 2 -2-tetrahydrofuran

Br

385

H

cyclopropylmethyl-

n-propyl

2-tetrahydrothienyl

Br

386

H

cyclopropylmethyl-

n-propyl

CH 2 OCH 3

I

387

H

cyclopropylmethyl-

n-propyl

CH 3

I

388

H

cyclopropylmethyl-

n-propyl

CH 2 OH

I

389

H

cyclopropylmethyl-

n-propyl

CH 2 N(CH 3 ) 2

I

390

H

cyclopropylmethyl-

n-propyl

CH 2 -N-piperdinyl

I

391

H

cyclopropylmethyl-

n-propyl

CH 2 -N-morpholinyl

I

392

H

cyclopropylmethyl-

n-propyl

cyclopropyl

I

393

H

cyclopropylmethyl-

n-propyl

CH 2 -cyclopropyl

I

394

H

cyclopropylmethyl-

n-propyl

2-tetrahydrofuranyl

I

395

H

cyclopropylmethyl-

n-propyl

CH 2 -2-tetrahydrofuran

I

396

H

cyclopropylmethyl-

n-propyl

2-tetrahydrothienyl

I

or a pharmaceutically acceptable salt thereof.

Assignments (3)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Feb 9, 2013
From: DOGWOOD PHARMACEUTICALS, INC.
To: ADENOSINE THERAPEUTICS, LLC
Reel/Frame 029785/0460 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jun 7, 2011
From: WANG, GUOQUAN; THOMPSON, ROBERT D.
To: ADENOSINE THERAPEUTICS LLC
Reel/Frame 026400/0078 →
CHANGE OF NAME Recorded Jan 28, 2011
From: PGXHEALTH, LLC
To: TROVIS PHARMACEUTICALS, LLC
Reel/Frame 025709/0994 →