Substituted pyrazoles, compositions containing such compounds and methods of use

1. A compound represented by formula I:

or a pharmaceutically acceptable salt thereof, wherein:

R′ is selected from the group consisting of:

(a) C 1-10 alkyl optionally substituted with: (1) 1-5 halo groups up to a perhaloalkyl group; (2) 1 oxo group; (3) 1-2 OH groups; (4) 1-2 C 1-10 alkoxy groups, each optionally substituted with: up to five halo or a perhaloalkoxy, 1 OH or C 2 R 8 group; (5) 1 C 2 R 8 or S(O) p R 7 ; (6) 1-2 Arl, Tetcy or HAR groups, each optionally substituted as follows: (i) 1-5 halo groups, (ii) 1 OH, CO 2 R 8 , CN, S(O) p R 7 , NO 2 or C(O)NR 9 R 10 group, (iii) 1-2 C 1-10 alkyl or alkoxy groups, each optionally substituted with: 1-5 halo, up to perhaloalkyl, and 1-2 OH or CO 2 R 8 groups; and (iv) 1-2 phenyl rings, each of which is optionally substituted as follows: 1-3 C 1-10 alkyl or alkoxy groups, each being further optionally substituted with 1-5 halo up to perhalo, or 1-2 hydroxy or CO 2 R 8 groups; (7) —NR 8 —C(O)—NR 9 R 10 ; (8) —NR 8 —CO 2 R 11 ; (9) —NR 8 —C(O)R 11 ; (10) —NR 9 R 10 ; (11) —NR 8 SO 2 R 11 ; NR 9 R 10 ; (13) —C(O)NR 9 R 10 and (14) —OC(O)—NR 9 R 10 ;

(b) Aryl optionally substituted as follows: (1) 1-3 C 1-10 alkyl, C 2-10 alkenyl or C 2-10 alkynyl groups optionally substituted with 1-5 halo groups, 1-2 OH, phenyl, CO 2 R 8 , CN or S(O) p R 7 groups; (2) 1-3 C 1-10 alkoxy groups, the alkyl portion of which is optionally substituted with 1-5 halo groups, 1-2 OH, phenyl, CO 2 R 8 , CN or S(O) p R 7 groups; (3) 1-2 Aryl, HAR or Hetcy groups, each optionally substituted as follows: (i) 1-3 halo groups; (ii) 1-2 C 1-10 alkyl, C 2-10 alkenyl or C 2-10 aykynyl groups each optionally substituted with 1-5 halo groups, 1-2 OH, phenyl, CO 2 R 11 , CN or S(O) p R 7 groups; (iii) 1-2 C 1-10 alkoxy groups the alkyl portion of which being optionally substituted with 1-5 halo groups, 1-2 OH, phenyl, CO 2 R 11 , CN or S(O) p R 7 groups; and (iv) 1-2 CO 2 R 11 , S(O) p R 7 , CN, NR 9 R 10 , NO 2 or OH groups;

said Aryl being further optionally substituted on carbon by a group selected from the group consisting of; (4) 1-5 halo groups; (5) 1-2 OH groups; (6) 1 S(O) p R 7 , NO 2 or CN group; (7) 1-2 CO 2 R 8 ; (8) —NR 8 —C(O)NR 9 R 10 ; (9) —NR 8 —CO 2 R 11 ; (10) —NR 8 —C(O)R 11 ; (11) —NR 9 R 10 ; (12) —NR 8 SO 2 R 11 ; (13) —SO 2 —NR 9 10 ; (14) —C(O)NR 9 R 10 and (15) —OC(O)—NR 9 R 10 ;

R 2 is H or R I as defined above;

R 3 and R 4 are H or C 1-10 alkyl;

R 5 represents H or F;

R 6 represents H, OH, F or C 1-3 alkyl, or R 5 and R 6 are taken in combination and represent oxo;

R 7 represents a member selected from the group consisting of: C 1-10 alkyl, Aryl or Ar-C 1-10 alkyl,

R 8 is H, C 1-10 alkyl, optionally substituted with phenyl, OH, OC 1-6 alkyl, CO 2 H, CO 2 C 1-6 alkyl and 1-3 halo groups;

R 9 is H or C 1-10 alkyl;

R 10 is H or is independently selected from: (a) C 1-10 alkyl, optionally substituted with OH, OC 1-6 alkyl, CO 2 H, CO 2 C 1-6 alkyl, and 1-3 halo groups; (b) Aryl or Ar-C 1-6 alkyl, each optionally substituted with 1-5 halos and 1-3 members selected from the group consisting of: CN, OH, C 1-10 alkyl and OC 1-10 alkyl, said alkyl and alkoxy being further optionally substituted with 1-5 halo groups up to perhalo; (c) Hetcy or Hetcy-C 1-6 alkyl, optionally substituted with 1-5 halo groups and 1-3 groups selected from: oxo, C 1-10 alkyl and OC 1-10 alkyl, said alkyl and alkoxy being further optionally substituted with 1-5 halo groups up to perhalo; and (d) HAR or HAR-C 1-6 alkyl, optionally substituted with 1-5 halo groups and 1-3 groups selected from: C 1-10 alkyl and OC 1-10 alkyl, said alkyl and alkoxy being further optionally substituted with 1-5 halo groups up to perhalo;

R 11 is independently selected from the group consisting of: (a) C 1-10 alkyl, optionally substituted with OH, OC 1-6 alkyl, CO 2 H, CO 2 C 1-6 alkyl, and 1-3 halo groups; (b) Aryl or Ar- 1-6 alkyl, each optionally substituted with 1-5 halos and 1-3 members selected from the group consisting of: CN, OH, C 1-10 alkyl and OC 1-10 alkyl, said alkyl and alkoxy being further optionally substituted with 1-5 halo groups up to perhalo; (c) Hetcy or Hetcy-C 1-6 alkyl, optionally substituted with 1-5 halo groups and 1-3 groups selected from: oxo, C 1-10 alkyl and OC 1-10 alkyl, said alkyl and alkoxy being further optionally substituted with 1-5 halo groups up to perhalo; and (d) HAR or HAR-C 1-6 alkyl, optionally substituted with 1-5 halo groups and 1-3 groups selected from: C 1-10 alkyl and OC 1-10 alkyl, said alkyl and alkoxy being further optionally substituted with 1-5 halo groups up to perhalo;

m is an integer sclectcd from 0, 1 and 2;

n is an integer selected from 0 to 6;

p is an integer selected from 0, 1 and 2, and

when at least one of m and n is other than 0, Z is selected from C 2 R 8 , 5-tetrazolyl and 5-(2-oxo-1,3,4-oxadiazolyl), and when both m and n are 0, Z is selected from 5-tetrazolyl and 5-(2-oxo-1,3,4-oxadiazolyl).

2. A compound in accordance with claim 1 or a pharmaceutically acceptable salt thereof wherein: R 1 is Aryl optionally substituted as set forth below:

(1) 1-3 C 1-10 alkyl or C 2-10 alkenyl groups optionally substituted with 1-5 halo groups, 1-2 OH, phenyl, CO 2 R 8 , CN or S(O) p R 7 groups;

(2) 1-3 C 1-10 alkoxy groups, the alkyl portion of which is optionally substituted with 1-5 halo groups, 1-2 phenyl, CN or S(O) p ,R 7 groups;

(3) 1-2 Aryl, HAR or Hetcy groups, each optionally substituted as follows: (i) 1-3 halo groups; (ii) 1-2 C 1-10 alkyl or C 2-10 alkenyl groups each optionally substituted with 1-5 halo groups, 1-2 OH, phenyl, CO 2 R 11 , CN or S(O) p R 7 groups; (iii) 1-2 C 1-10 alkoxy groups the alkyl portion of which being optionally substituted with 1-5 halo groups, 1-2 phenyl, CO 2 R 11 , CN or S(O) p R 7 groups; and (iv) 1-2 CO 2 R 11 , S(O) p R 7 , CN, NR 9 R 10 , NO 2 or OH groups;

(4) 1-5 halo groups;

(5) 1-2 OH groups;

(6) 1 S(O) p R 7 , NO 2 or CN group;

(7) 1-2 CO 2 R 8 ;

(8) —NR 8 —C(O)—NR 9 R 10 ;

(9) —NR 8 —CO 2 R 11 ;

(10) —NR 8 —C(O)R 11 ;

(11) —NR 9 R 10 ;

(12) —NR 8 SO 2 R 11 ;

(13) —SO 2 —NR 9 R 10 ;

(14) —C(O)NR 9 R 10 and

(15) —OC(O)—NR 9 R 10 .

3. A compound in accordance with claim 2 or a pharmaceutically acceptable salt thereof wherein R 1 is Phenyl optionally substituted as follows: (1) 1 C 1-3 alkyl group optionally substituted with 1-3 halo groups, 1 phenyl or S(O) p R 7 group; (2) 1 C 1-3 alkoxy group, the alkyl portion of which is optionally substituted with 1-3 halo groups or 1 phenyl group; (3) 1 phenyl, pyridinyl, isoxazolyl or piperidinyl group, each optionally substituted as follows: (i) 1-3 halo groups; (ii) 1 C 1-6 alkyl group optionally substituted with 1-3 halo or 1 hydroxy group; (iii) 1 C 1-6 alkoxy group the alkyl portion of which being optionally substituted with 1-3 halo groups; and (iv) 1 CO 2 R 11 , S(O) p R 7 , CN, NR 9 R 10 , NO 2 or OH group; (4) 1-3 halo groups; (5) 1 OH group; (6) 1 S(O) p R 7 , NO 2 or CN group; (7) 1 CO 2 R 8 ; (8) —NR 9 R 10 ; (9) —C(O)NR 9 R 10 and (10) —OC(O)—NR 9 R 10 .

4. A compound in accordance with claim 3 or a pharmaceutically acceptable salt thereof wherein R 1 is Phenyl optionally substituted as follows:

(1) 1 C 1-3 alkyl group optionally substituted with 1-3 halo groups or 1 phenyl group; (2) 1 C 1-3 alkoxy group, the alkyl portion of which is optionally substituted with 1-3 halo groups or 1 phenyl group; (3) 1 phenyl, pyridinyl or isoxazolyl group, each optionally substituted as follows: (i) 1-3 halo groups; (ii) 1 C 1-6 alkyl group optionally substituted with 1-3 halo or 1 hydroxy group; (iii) 1 C 1-6 alkoxy group the alkyl portion of which being optionally substituted with 1-3 halo groups; and (iv) 1 CO 2 R 11 , S(O) p R 7 , CN, NR 9 R 10 , NO 2 or OH group; (4) 1-3 halo groups; (5) 1 OH group; (6) 1 CO 2 R 8 ; and (7) —NR 9 R 10 .

5. A compound in accordance with claim 1 or a pharmaceutically acceptable salt thereof wherein R 1 , R 3 through R 11 , m, n, p and Z are as defined therein, and

R 2 is selected from the group consisting of:

a) C 1-10 alkyl optionally substituted with: (1) 1-5 halo groups upto a perhaloalkyl group; (2) 1-2 OH groups; (3) 1-2 C 1-10 alkoxy groups, each optionally substituted with up to five halo or a perhaloalkoxy group; (4) 1 CO 2 R 8 or S(O) p R 7 ; (5) 1-2 Aryl, Hetcy or HAR, groups, each optionally substituted as follows: (a) 1-5 halo groups, (b) 1 OH, CO 2 R 8 , CN, S(O) p R 7 , NO 2 or C(O)NR 9 R 10 group , (c) 1-2 C 1-10 alkyl or alkoxy groups, each optionally substituted with: 1-5 halo, up to perhaloalkyl, and 1-2 OH or CO 2 R 8 groups; and (d) 1-2 phenyl rings, each of which is optionally substituted as follows: 1-3 C 1-10 alkyl or alkoxy groups, each being further optionally substituted with 1-5 halo up to perhalo, or 1-2 hydroxy or CO 2 R 8 groups; and

b) Aryl optionally substituted as follows: (1) 1-3 C 1-10 alkyl or C 2-10 alkenyl groups optionally substituted with 1-5 halo groups, 1-2 OH, phenyl, CO 2 R 8 , CN or S(O) p R 7 groups; (2) 1-3 C 1-10 alkoxy groups, the alkyl portion of which is optionally substituted with 1-5 halo groups, 1-2 phenyl, CN or S(O) p R 7 groups; (3) 1-2 Aryl, HAR or Hetcy groups, each optionally substituted as follows: (i) 1-3 halo groups; (ii) 1-2 C 1-10 alkyl or C 2-10 alkenyl groups each optionally substituted with 1-5 halo groups, 1-2 OH, phenyl, CO 2 R 11 , CN or S(O) p R 7 groups; (iii) 1-2 C 1-10 alkoxy groups the alkyl portion of which being optionally substituted with 1-5 halo groups, 1-2 phenyl, CO 2 R 11 , CN or S(O) p R 7 groups; and (iv) 1-2 CO 2 R 11 , S(O) p R 7 , CN, NR 9 R 10 , NO 2 or OH groups; (4) 1-5 halo groups; (5) 1-2 OH groups; (6) 1 S(O) p R 7 , NO 2 or CN group; (7) 1-2 CO 2 R 8 ; (8) —NR 8 —C(O)—NR 9 R 10 ; (9) —NR 8 —CO 2 R 11 ; (10) —NR 8 —C(O)R 11 ; (11) —NR 9 10 ; (12) —NR 8 SO 2 R 11 ; —SO 2 —NR 9 R 10 ; (14) —C(O)NR 9 R 10 and (15) —OC(O)—NR 9 R 10 .

6. A compound in accordance with claim 5 or a pharmaceutically acceptable salt thereof wherein R 2 is selected from the group consisting of:

a) C 1-10 alkyl optionally substituted with: (1) 1-2 halo groups; (2) 1-2 C 1-6 alkoxy groups, each optionally substituted with up to 3 halo groups; (3) 1 Phenyl, Piperidinyl or Pyridinyl group, each optionally substituted as follows: (i) 1-2 halo groups, (ii) 1-2 C 1-3 alkyl or alkoxy groups, each optionally substituted with: 1-3 halo groups; and (iii) 1 phenyl ring, optionally substituted with 1-3 C 1-3 alkyl or alkoxy groups, each being further optionally substituted with 1-3 halo groups; and

b) Phenyl optionally substituted as follows: (1) 1 C 1-3 alkyl group optionally substituted with 1-3 halo groups, 1 phenyl or S(O) p R 7 group; (2) 1 C 1-3 alkoxy group, the alkyl portion of which is optionally substituted with 1-3 halo groups or 1 phenyl group; (3) 1 phenyl, pyridinyl, isoxazolyl or piperidinyl group, each optionally substituted as follows: (i) 1-3 halo groups; (ii) 1 C 1-6 alkyl group optionally substituted with 1-3 halo or 1 hydroxy group; (iii) 1 C 1-6 alkoxy group the alkyl portion of which being optionally substituted with 1-3 halo groups; and (iv) 1 CO 2 R 11 , S(O) p R 7 , CN, NR 9 R 10 , NO 2 or OH group; (4) 1-3 halo groups; (5) 1 OH group; (6) 1 S(O) p R 7 , NO 2 or CN group; (7) 1 CO 2 R 8 ; (8) —NR 9 R 10 ; (9) —C(O)NR 9 R 10 and (10) —OC(O)—NR 9 R 10 .

7. A compound in accordance with claim 6 or a pharmaceutically acceptable salt thereof wherein:

R 2 is selected from the group consisting of:

a) C 1-10 alkyl optionally substituted with: Phenyl, optionally substituted as follows: (i) 1-2 halo groups, (ii) 1-2 C 1-3 alkyl or alkoxy groups, each optionally substituted with: 1-3 halo groups; and (iii) 1 phenyl ring, optionally substituted with 1-3 C 1-3 alkyl or alkoxy groups, each being further optionally substituted with 1-3 halo groups;

b) Phenyl optionally substituted as follows: (1) 1 C 1-3 alkyl group optionally substituted with 1-3 halo groups or 1 phenyl group; (2) 1 C 1-3 alkoxy group, the alkyl portion of which is optionally substituted with 1-3 halo groups or 1 phenyl group; (3) 1 phenyl, pyridinyl or isoxazolyl group, each optionally substituted as follows: (i) 1-3 halo groups; (ii) 1 C 1-6 alkyl group optionally substituted with 1-3 halo or 1 hydroxy group; (iii) 1 C 1-6 alkoxy group the alkyl portion of which being optionally substituted with 1-3 halo groups; and (iv) 1 CO 2 R 11 , S(O) p R 7 , CN, NR 9 R 10 , NO 2 or OH group; (4) 1-3 halo groups; (5) 1 OH group; (6) 1 CO 2 R 8 ; and (7) —NR 9 R 10 .

8. A compound in accordance with claim 1 or a pharmaceutically acceptable salt thereof wherein R 3 represents H or methyl.

9. A compound in accordance with claim 1 or a pharmaceutically acceptable salt thereof wherein R 4 represents H or methyl.

10. A compound in accordance with claim 9 or a pharmaceutically acceptable salt thereof wherein R 4 represents H.

11. A compound in accordance with claim 1 or a pharmaceutically acceptable salt thereof wherein n represents 1 or 2; m represents 0 and Z is selected from CO 2 R 8 and 5-tetrazolyl.

12. A compound in accordance with claim 11 or a pharmaceutically acceptable salt thereof wherein n represents 1 or 2; m represents 0 and Z represents 5-tetrazolyl.

13. A compound in accordance with claim 11 or a pharmaceutically acceptable salt thereof wherein: n represents 1 or 2; m represents 0 and Z represents CO 2 R 8 .

14. A compound in accordance with claim 1 or a pharmaceutically acceptable salt thereof wherein R 8 is H or C 1-10 alkyl, optionally substituted with phenyl or 1-3 halo groups.

15. A compound in accordance with claim 1 selected from the group consisting of:

Cpd No.

Structure

1

2

3

4

5

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

75

76

78

79

80

81

82

83

84

85

86

87

88

89

90

91

92

93

94

95

96

97

98

99

100

101

115

116

117

118

137

138

139

140

141

142

143

144

145

146

147

148

149

150

151

152

153

154

155

156

157

158

159

160

161

162

163

164

165

166

167

168

169

170

171

or a pharmaceutically acceptable salt thereof.

16. A pharmaceutical composition comprising a compound in accordance with claim 1 or a pharmaceutically acceptable salt thereof in combination with a phannaceutically acceptable carrier.