Substituted pyrazoles, compositions containing such compounds and methods of use

1. A compound represented by formula I:

or a pharmaceutically acceptable salt or solvate thereof, wherein:

A represents a 9-10 membered bicyclic heteroaryl group containing 1-4 heteroatoms, 0-4 of which are N and 0-1 of which are O or S,

said bicyclic heteroaryl group being optionally substituted as follows:

e) 1-5 halo groups;

f) 1 CO 2 R a ; S(O) p R d ; OH, CN, NO 2 ; C(O)NR b R c and NR b R c ;

c) 1-2 C 1-10 alkyl or OC 1-10 alkyl, said groups being 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 CO 2 R a group;

(5) 1 CO 2 R a or S(O) p R d ;

(6) 1-2 Aryl, Hetcy or HAR groups, each optionally substituted as follows:

(a) 1-5 halo groups,

(b) 1 OH, CO 2 R a , CN, S(O) p R d , NO 2 or C(O)NR b R c , and

(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 a groups; and

d) Aryl, HAR, Hetcy, each optionally substituted as set forth below:

(1) 1-3 C 1-10 alkyl or alkoxy groups optionally substituted as follows: 1-5 halo groups; 1-2 OH groups; CO 2 R a ; CN; S(O) p R d ; phenyl optionally substituted as follows: (i) 1-5 halo groups, (ii) 1 CO 2 R a , CN, S(O) p R d , NO 2 or C(O)NR b R c 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 a groups; and

said Aryl, HAR, Hetcy group d) being further optionally substituted on carbon by a group selected from the group consisting of;

(2) 1-5 halo groups;

(3) 1-2 OH groups;

(4) 1 S(O) p R d , NO 2 or CN group;

(5) 1-2 CO 2 R a ; and

(6) —C(O)NR b R c ;

R a is H or 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 b is H or C 1-10 alkyl;

R c 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 d is C 1-10 alkyl, Aryl or Ar—C 1-10 alkyl; and

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

each R 1 represents H or is selected from the group consisting of:

a) halo; CO 2 R a ; S(O) p R d ; OH, CN, NO 2 ; C(O)NR b R c and NR b R c ;

b) C 1-10 alkyl or OC 1-10 alkyl, said groups being 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 CO 2 R a group;

(5) 1 CO 2 R a or S(O) p R d ;

(6) 1-2 Aryl, Hetcy or HAR groups, each optionally substituted as follows:

(a) 1-5 halo groups,

(b) 1 OH, CO 2 R a , CN, S(O) p R d , NO 2 or C(O)NR b R c , and

(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 a groups;

c) Aryl, HAR, Hetcy, each optionally substituted as set forth below:

(1) 1-3 C 1-10 alkyl or alkoxy groups optionally substituted as follows: 1-5 halo groups; 1-2 OH groups; CO 2 R a ; CN; S(O) p R d , phenyl optionally substituted as follows: (i) 1-5 halo groups, (ii) 1 CO 2 R a , CN, S(O) p R d , NO 2 or C(O)NR b R c 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 a groups; and

said Aryl, HAR, Hetcy group c) being further optionally substituted on carbon by a group selected from the group consisting of;

(2) 1-5 halo groups;

(3) 1-2 OH groups;

(4) 1 S(O) p R d , NO 2 or CN group;

(5) 1-2 CO 2 R a ; and

(6) —C(O)NR b R c ,

wherein R a , R b , R c , R d , and p are as previously defined, and

R 2 is selected from hydrogen and C 1-6 alkyl.

2. A compound in accordance with claim 1 wherein:

A represents a 9-10 membered bicyclic heteroaryl group containing 1-3 heteroatoms, 0-3 of which are N and 0-1 of which are O or S,

said bicyclic heteroaryl group being optionally substituted as follows:

a) 1-5 halo groups;

b) 1 CO 2 R a ; S(O) p R d ; OH, CN;

c) 1-2 C 1-10 alkyl or OC 1-10 alkyl, said groups being optionally substituted with:

(1) 1-5 halo groups up to a perhaloalkyl group;

(2) 1-2 C 1-10 alkoxy groups, each optionally substituted with:

up to five halo or a perhaloalkoxy, 1 OH or CO 2 R a group.

3. A compound in accordance with claim 1 wherein:

each R 1 represents H or is selected from the group consisting of:

a) halo; CO 2 R′; S(O) p R d ; OH, CN;

b) C 1-10 alkyl or OC 1-10 alkyl, said groups being 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 CO 2 R a group; and

(5) 1 CO 2 R a or S(O) p R d .

4. A compound in accordance with claim 1 wherein

A represents a 9-10 membered bicyclic heteroaryl group containing 1-3 heteroatoms, 0-3 of which are N and 0-1 of which are O or S,

said bicyclic heteroaryl group being optionally substituted as follows:

a) 1-5 halo groups;

b) 1 CO 2 R a ; S(O) p R d ; OH, CN;

c) 1-2 C 1-10 alkyl or OC 1-10 alkyl, said groups being optionally substituted with:

(1) 1-5 halo groups up to a perhaloalkyl group;

(2) 1-2 C 1-10 alkoxy groups, each optionally substituted with:

up to five halo or a perhaloalkoxy, 1 OH or CO 2 R a group; and

each R 1 represents H or is selected from the group consisting of:

a) halo; CO 2 R a ; S(O) p R d ; OH, CN;

b) C 1-10 alkyl or OC 1-10 alkyl, said groups being 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 Cl 1-10 alkoxy groups, each optionally substituted with:

up to five halo or a perhaloalkoxy, 1 OH or CO 2 R a group; and

(5) 1 CO 2 R a or S(O) p R d .

5. A compound in accordance with claim 1 wherein:

A represents a 9-10 membered bicyclic heteroaryl group selected from the group consisting of: indole, benzimidazole, benzthiazole, benzoxazole, benzofuran, quinoline, isoquinoline and quinaxoline,

said group being optionally substituted as follows:

a) 1-5 halo groups

b) 1 OH group;

c) 1-2 C 1-10 alkyl or OC 1-10 alkyl groups, said groups being optionally substituted with 1-5 halo groups, up to perhaloalkyl;

and each R1 represents H or is selected from the group consisting of:

a) halo;

b) C 1-10 alkyl or OC 1-10 alkyl, optionally substituted with 1-5 halo groups up to perhaloalkyl; and

R 2 is H or methyl.

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

TABLE 1

A

R 1

3,5-dichloro

3,5-dichloro

3,5-dichloro

2Cl-5-CF 3

3,5-dichloro

3,5-dichloro

3,5-dichloro

3,5-dichloro

2F-5-CF 3

2F-5-CF 3

2F-5-CF 3

3,4-dichloro

3,4-dichloro

3,4-dichloro

2F-4-CF 3

2Cl-5-CF 3

3,5-dichloro

3,5-dichloro

3,5-dichloro

3,4-dichloro

2F-4-CF 3

3,5-dichloro

3,4-dichloro

3,5-dichloro

2Cl-5-CF 3

2-F-4-CF 3

2-Cl-5-CF 3

3,5-dichloro

2-F-4-CF 3

2-Cl-5-CF 3

3,5-dichloro

3,4-dichloro

2-Cl-5-CF 3

or a pharmaceutically acceptable salt or solvate thereof.

7. A pharmaceutical composition comprising a compound in accordance with claim 1 in combination with a pharmaceutically acceptable carrier.

8. A method of treating type 2 diabetes mellitus in a mammalian patient in need of such treatment comprising administering to said patient a compound in accordance with claim 1 in an amount that is effective to treat said type 2 diabetes mellitus.

9. A method of treating atherosclerosis in a mammalian patient in need of such treatment, comprising administering to said patient a compound in accordance with claim 1 in an amount effective to treat atherosclerosis.