Substituted cyclopropyl compounds, compositions containing such compounds and methods of treatment

1. A compound represented by the formula:

or a pharmaceutically acceptable salt thereof, wherein:

ring A is phenyl or a 6-membered heteroaryl, containing 1-2 N atoms;

B is a member selected from the group consisting of

(1) C(O)R 3 ,

(2) C(O)OR 3 ,

(3) C(O)NHR 3 , and

(4) 5-membered heteroaryl containing 1-4 heteroatoms selected from O, S and N, wherein the 5-membered heteroaryl ring can be optionally fused with a 5- or 6-membered ring system; which can be optionally substituted with 1-3 R 4 ;

R 1 represents a member selected from the group consisting of

(1) 3- to 6-membered heterocyclyl, containing 1-3 O, S, or N,

(2) 5-membered heteroaryl, containing 1-4 O, S, or N,

(3) aryl,

(4) C(O)C 1-6 alkyl,

(5) C(O)C 3-8 cycloalkyl,

(6) S(O)C 1-6 alkyl,

(7) SO 2 C 1-6 alkyl,

(8) SO 2 NH 2 ,

(9) SO 2 C 3-8 cycloalkyl,

(10) SO 2 NHC 1-6 alkyl,

(11) SO 2 N(C 1-6 alkyl) 2 ,

(12) CN,

(13) C(O)NR 8 R 9 , and

(14) CH 2 C(O)NR 5 R 6 ,

wherein the heterocyclyl and heteroaryl moieties are optionally substituted by oxo, hydroxy, C 1-3 alkyl, C 1-3 alkoxy, or haloC 1-3 alkyl, and the heterocyclyl moiety is further optionally substituted by oxo;

each R 2 is independently selected from the group consisting of

(1) halogen,

(2) C 1-6 alkyl,

(3) —OC 1-6 alkyl,

(4) CN, and

(5) haloC 1-6 alkyl;

R 3 represents a member selected from the group consisting of:

(1) C 1-6 alkyl,

(2) haloC 1-6 alkyl,

(3) C 3-8 cycloalkyl and

(4) aryl,

wherein alkyl is optionally substituted with 1-2 of C 3-8 cycloalkyl, phenyl, or 5-membered heteroaryl containing 1-3 O, S, or N; and wherein the cycloalkyl is optionally fused with a C 3-6 cycloalkyl or C 3-6 cycloalkenyl;

R 4 is selected from the group consisting of:

(1) hydroxy,

(2) C 1-6 alkyl,

(3) C 1-6 alkoxy,

(4) C 1-6 alkyl-O—C 1-3 alkyl,

(5) C 1-6 alkyl-O-haloC 1-3 alkyl,

(6) C 3-6 cycloalkyl, optionally substituted by C 1-3 alkyl or haloC 1-3 alkyl,

(7) C 3-6 cycloalkoxy, and

(8) aryl,

wherein the alkyl moiety is optionally substituted by 1-3 halo, or hydroxy;

R 5 and R 6 are independently selected from the group consisting of

(1) hydrogen,

(2) C 1-6 alkyl,

(3) C 3-6 cycloalkyl, optionally substituted by halo, haloalkyl, or alkyl

(4) C 1-6 alkyl-OH,

(5) C 1-3 alkyl-C 3-6 cycloalkyl,

(6) C 1-3 alkyl-C 3-5 heterocyclyl containing 1-3 N, O, or S,

(7) C 3-5 heterocyclyl containing 1-3 N, O or S, optionally substituted by 1-2 oxo, or alkyl,

(8) C 1-3 alkyl-5-membered heteroaryl containing 1-3 N, O or S, optionally substituted by C 1-3 alkyl,

(9) haloC 1-6 alkyl,

or R 5 and R 6 are linked together with the nitrogen to which they are both attached to form a 4-9 membered monocyclic or bicyclic heterocyclic ring, comprising C, O, N, and S ring atoms, wherein the heterocyclic ring is optionally substituted with 1-3 R 7 ;

each R 7 is selected from the group consisting of:

(1) halo,

(2) hydroxy,

(3) C 1-3 alkoxy,

(4) C 1-3 alkyl,

(5) haloC 1-3 alkyl,

(6) C 1-3 alkyl-OH,

(7) C 3-6 cycloalkyl,

(8) 5- or 6-membered heteroaryl, containing 1-3 N, O, or S, and

(9) oxo;

R 8 and R 9 are independently selected from the group consisting of

(1) hydrogen,

(2) C 1-6 alkyl,

(3) C 1-6 alkyl-OH, and

(4) C 3-8 cycloalkyl; and

i and j independently represent integers selected from 0, 1 and 2, such that i plus j is 0, 1 or 2.

2. The compound of claim 1 , wherein ring A is phenyl, pyridinyl, pyrimidinyl, pyridazinyl, or pyrazinyl.

3. The compound of claim 1 , wherein ring A is phenyl or pyrimidine.

4. The compound of claim 1 , wherein ring A is a pyridine ring.

5. The compound of claim 1 , wherein B is selected from the group consisting of:

wherein C is any 5-membered heteroaryl moiety and r is an integer selected from 1 or 2.

6. The compound of claim 1 , wherein B is selected from the group consisting of

7. The compound of claim 6 , wherein R 4 is selected from the group consisting of

8. The compound of claim 1 , wherein B is C(O)R 3 , or C(O)OR 3 .

9. The compound of claim 8 , wherein B is selected from the group consisting of

10. The compound of claim 1 , wherein R 1 represents a member selected from the group consisting of 3- to 6-membered heterocyclyl, containing 1-3 O, S, or N, optionally substituted by oxo; 5-membered heteroaryl, containing 1-4 O, S, or N, optionally substituted by C 1-3 alkyl; aryl; C(O)C 1-6 alkyl; C(O)C 3-8 cycloalkyl; SO 2 C 1-6 alkyl; SO 2 C 3-8 cycloalkyl; CN; C(O)NR 8 R 9 ; and CH 2 C(O)NR 5 R 6 .

11. The compound of claim 10 , wherein R 1 is 5-membered heteroaryl, containing 1-4 O, S, or N, optionally substituted by C 1-3 alkyl.

12. The compound of claim 11 , wherein R 1 is SO 2 C 1-6 alkyl, or SO 2 C 3-8 cycloalkyl.

13. The compound of claim 12 , wherein R 1 is C(O)NR 8 R 9 or CH 2 C(O)NR 5 R 6 .

14. The compound of claim 1 , wherein each R 2 is methyl, chloro, fluoro, CN, or methoxy.

15. A compound represented by the formula I-G:

or a pharmaceutically acceptable salt thereof, wherein:

R 1 represents a member selected from the group consisting of

(1) 3- to 6-membered heterocyclyl, containing 1-3 O, S, or N,

(2) 5-membered heteroaryl, containing 1-4 O, S, or N,

(3) C(O)C 1-6 alkyl,

(4) C(O)C 3-8 cycloalkyl,

(5) SO 2 C 1-6 alkyl,

(6) CN,

(7) C(O)NR 8 R 9 , and

(8) CH 2 C(O)NR 5 R 6 ,

wherein the heterocyclyl and heteroaryl moieties are optionally substituted by oxo, hydroxy, C 1-3 alkyl, C 1-3 alkoxy, or haloC 1-3 alkyl, and the heterocyclyl moiety is further optionally substituted by oxo;

each R 2 is independently selected from the group consisting of

(1) halogen,

(2) C 1-6 alkyl,

(3) —OC 1-6 alkyl, and

(4) CN;

R 4 is selected from the group consisting of:

(1) hydroxy,

(2) C 1-6 alkyl,

(3) C 1-6 alkoxy,

(4) C 1-6 alkyl-O—C 1-3 alkyl,

(5) C 1-6 alkyl-O-haloC 1-3 alkyl,

(6) C 3-6 cycloalkyl, optionally substituted by C 1-3 alkyl or haloC 1-3 alkyl,

(7) C 3-6 cycloalkoxy, and

(8) aryl,

wherein the alkyl moiety is optionally substituted by 1-3 halo, or hydroxy;

R 5 and R 6 are independently selected from the group consisting of

(1) hydrogen,

(2) C 1-6 alkyl,

(3) C 3-6 cycloalkyl, optionally substituted by halo, haloalkyl, or alkyl

(4) C 1-6 alkyl-OH,

(5) C 1-3 alkyl-C 3-6 cycloalkyl,

(6) C 1-3 alkyl-C 3-5 heterocyclyl containing 1-3 N, O, or S,

(7) C 3-5 heterocyclyl containing 1-3 N, O or S, optionally substituted by 1-2 oxo, or alkyl,

(8) C 1-3 alkyl-5-membered heteroaryl containing 1-3 N, O or S, optionally substituted by C 1-3 alkyl,

(9) haloC 1-6 alkyl,

or R 5 and R 6 are linked together with the nitrogen to which they are both attached to form a 4-9 membered monocyclic or bicyclic heterocyclic ring, comprising C, O, N, and S ring atoms, wherein the heterocyclic ring is optionally substituted with 1-3 R 7 ;

each R 7 is selected from the group consisting of:

(1) halo,

(2) hydroxy,

(3) C 1-3 alkoxy,

(4) C 1-3 alkyl,

(5) haloC 1-3 alkyl,

(6) C 1-3 alkyl-OH,

(7) C 3-6 cycloalkyl,

(8) 5- or 6-membered heteroaryl, containing 1-3 N, O, or S, and

(9) oxo; and

R 8 and R 9 are independently selected from the group consisting of

(1) hydrogen,

(2) C 1-6 alkyl,

(3) C 1-6 alkyl-OH, and

(4) C 3-8 cycloalkyl.

16. A compound of claim 1 or a pharmaceutically acceptable salt thereof, selected from the group consisting of:

17. A pharmaceutical composition comprising a compound of claim 1 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

18. A method for the treatment of a condition selected from the group consisting of obesity and diabetes comprising administering to an individual a pharmaceutical composition comprising the compound of claim 1 .