Antidiabetic bicyclic compounds

1. A compound of structural formula I:

or a pharmaceutically acceptable salt thereof; wherein

A is pyrazine, wherein pyrazine is unsubstituted or substituted with one to two substituents selected from Ra, provided that one of R a and R 4 is not hydrogen;

B is selected from the group consisting of:

(1) aryl, and

(2) heteroaryl,

wherein B is unsubstituted or substituted with one to five substituents selected from R b ;

each R 1 is independently selected from the group consisting of:

(1) —C 1-10 alkyl,

(2) —C 2-10 alkenyl,

(3) —C 2-10 alkynyl, and

(4) —C 3-6 cycloalkyl,

wherein each alkyl, alkenyl, alkynyl and cycloalkyl is unsubstituted or substituted with 1-4 substituents selected from C 1-6 alkyl, halogen, and —OC 1-6 alkyl;

each R 2 is independently selected from the group consisting of:

(1) —C 1-10 alkyl,

(2) —C 2-10 alkenyl,

(3) —C 2-10 alkynyl,

(4) —C 3-6 cycloalkyl,

(5) —C 2-6 cycloheteroalkyl,

(6) aryl, and

(7) heteroaryl,

wherein each alkyl, alkenyl, alkynyl, cycloalkyl, cycloheteroalkyl, aryl and heteroaryl is unsubstituted or substituted with 1-4 substituents selected from C 1-6 alkyl, halogen, and —OC 1-6 alkyl;

R 3 is selected from the group consisting of:

(1) hydrogen,

(2) halogen, and

(3) —C 1-6 alkyl;

R 4 is selected from the group consisting of:

(1) hydrogen,

(2) C 1-6 alkyl, and

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

R 5 is selected from the group consisting of:

(1) —CO 2 R 6 , and

(2) —C(O)NR c R d ;

R6 is selected from the group consisting of:

(1) hydrogen,

(2) —C 1-6 alkyl,

(3) —C 3-6 cycloalkyl, and

(4) aryl—C 1-6 alkyl,

wherein each alkyl, cycloalkyl and aryl is unsubstituted or substituted with one to three substituents selected from R h ;

R a is selected from the group consisting of:

(1) hydrogen,

(2) —C 1-3 alkyl,

(3) —CF 3 , and

(4) —C 3-6 cycloalkyl,

wherein each alkyl and cycloalkyl is unsubstituted or substituted with one to three substituents selected from: —C 1-3 alkyl, halogen and —CF 3 ;

R b is independently selected from the group consisting of:

(1) —C 1-10 alkyl,

(2) —CF 3 ,

(3) halogen,

(4) —CN,

(5) —OH,

(6) —OC 1-10 alkyl,

(7) —O(CH 2 )pOC 1-10 alkyl,

(8) —O(CH 2 )pC 3-6 cycloalkyl,

(9) —O(CH 2 )pC 2-5 cycloheteroalkyl,

(10) —O(CH 2 )pNR c R d ,

(11) —O(CH 2 )pO—C 3-6 cycloalkyl,

(12) —OCF 3 ,

(13) —OCHF 2 ,

(14) —(CH 2 )pC 3-6 cycloalkyl, and

(15) —(CH 2 )pC 2-5 cycloheteroalkyl,

wherein each CH, CH 2 , alkyl, alkenyl, cycloalkyl, cycloheteroalkyl, aryl and heteroaryl is unsubstituted or substituted with one to five substituents selected from: —C 1-6 alkyl, halogen, —O—C 1-6 alkyl and —CF 3 ;

R c and R d are each independently selected from the group consisting of:

(1) hydrogen,

(2) C 1-10 alkyl,

(3) C 3-6 cycloalkyl,

(4) C 3-6 cycloalkyl-C 1-10 alkyl-,

(5) C 2-5 cycloheteroalkyl,

(6) aryl-C 1-10 alkyl-, and

(7) heteroaryl-C 1-10 alkyl-,

wherein each alkyl, cycloalkyl, cycloheteroalkyl, aryl and heteroaryl is unsubstituted or substituted with one to three substituents independently selected from R f ,

or R c and R d together with the atom(s) to which they are attached form a C 2-5 cycloheteroalkyl ring containing 0-2 additional heteroatoms independently selected from oxygen, sulfur and N—R g , wherein each R c and R d is unsubstituted or substituted with one to three substituents independently selected from R f ;

each R e is independently selected from the group consisting of:

(1) hydrogen,

(2) —C 1-10 alkyl,

(3) —C 3-6 cycloalkyl, and

(4) —C 2-5 cycloheteroalkyl;

each R f is selected from the group consisting of:

(1) halogen,

(2) C 1-10 alkyl,

(3) —OH,

(4) —O—C 1-4 alkyl,

(5) —S(O) m —C 1-4 alkyl,

(6) —CN,

(7) —CF 3 ,

(8) —OCHF 2 , and

(9) —OCF 3 ,

wherein each alkyl is unsubstituted or substituted with one to three substituents independently selected from: —OH, halogen, and C 1-6 alkyl;

each R g is selected from the group consisting of:

(1) hydrogen, and

(2) —C 1-10 alkyl,

wherein each alkyl is unsubstituted or substituted with one to five halogens;

R h is independently selected from the group consisting of:

(1) —C 1-6 alkyl,

(2) —OR e ,

(3) —NR c S(O) m R e ,

(4) halogen,

(5) —S(O) m R e ,

(6) —S(O) m NR c R d ,

(7) —NR c R d ,

(8) —C(O)R e ,

(9) —OC(O)R e ,

(10) —CO 2 R e ,

(11) —CN,

(12) —C(O)NR c R d ,

(13) —NR c C(O)R e ,

(14) —NR c C(O)OR e ,

(15) —NR c C(O)NR c R d ,

(16) —CF 3 ,

(17) —OCF 3 ,

(18) —OCHF 2 ,

(19) —C 3-6 cycloalkyl, and

(20) —C 2-5 cycloheteroalkyl;

each m is independently selected from: 0, 1 and 2;

each p is independently selected from: 0, 1, 2, 3, 4, 5 and 6;

each q is independently selected from 0, 1, 2 and 3;

each u is independently selected from 0, 1 and 2;

each r is independently selected from 0 and 1; and

each s is independently selected from 0 and 1.

2. The compound according to claim 1 wherein A is pyrazine, wherein pyrazine is substituted with one to two substituents selected from R a ; or a pharmaceutically acceptable salt thereof.

3. The compound according to claim 1 wherein A is pyrazine, wherein pyrazine is substituted with one substituent selected from R a ; or a pharmaceutically acceptable salt thereof.

4. The compound according to claim 1 wherein B is heteroaryl, wherein heteroaryl is unsubstituted or substituted with one to five substituents selected from R b ; or a pharmaceutically acceptable salt thereof.

5. The compound according to claim 1 wherein B is pyridine, wherein pyridine is unsubstituted or substituted with one to five substituents selected from R b ; or a pharmaceutically acceptable salt thereof.

6. The compound according to claim 1 wherein R 1 is —C 1-10 alkyl, wherein alkyl is unsubstituted or substituted with 1-4 substituents selected from C 1-6 alkyl, halogen, and —OC 1-6 alkyl; or a pharmaceutically acceptable salt thereof.

7. The compound according to claim 1 wherein R 1 is —C 1-3 alkyl; or a pharmaceutically acceptable salt thereof.

8. The compound according to claim 1 wherein R 2 is independently selected from the group consisting of: —C 3-6 cycloalkyl, wherein cycloalkyl is unsubstituted or substituted with 1-4 substituents selected from C 1-6 alkyl, halogen, and —OC 1-6 alkyl; or a pharmaceutically acceptable salt thereof.

9. The compound according to claim 1 wherein R 2 is cyclopropyl, wherein cycloalkyl is unsubstituted or substituted with 1-4 substituents selected from C 1-6 alkyl, halogen, and —OC 1-6 alkyl; or a pharmaceutically acceptable salt thereof.

10. The compound according to claim 1 wherein R 3 is selected from the group consisting of: hydrogen and halogen; or a pharmaceutically acceptable salt thereof.

11. The compound according to claim 1 wherein R 3 is halogen; or a pharmaceutically acceptable salt thereof.

12. The compound according to claim 1 wherein R 4 is hydrogen or C 1-6 alkylO—; or a pharmaceutically acceptable salt thereof.

13. The compound according to claim 1 wherein R 5 is —CO 2 R 6 ; and R 6 is selected from the group consisting of: hydrogen and —C 1-6 alkyl, wherein each alkyl is unsubstituted or substituted with one to three substituents selected from R h ; or a pharmaceutically acceptable salt thereof.

14. The compound according to claim 13 wherein R 5 is —CO 2 R 6 ; and R 6 is hydrogen; or a pharmaceutically acceptable salt thereof.

15. The compound according to claim 1 of structural Formula Ik:

wherein

A is pyrazine, wherein pyrazine is unsubstituted or substituted with one to two substituents selected from R a ;

B is heteroaryl, wherein heteroaryl is unsubstituted or substituted with one to five substituents selected from R b ;

R 1 is —C 1-10 alkyl, wherein alkyl is unsubstituted or substituted with 1-4 substituents selected from C 1-6 alkyl, halogen, and —OC 1-6 alkyl;

R 2 is independently selected from the group consisting of: —C 3-6 cycloalkyl, wherein cycloalkyl is unsubstituted or substituted with 1-4 substituents selected from C 1-6 alkyl, halogen, and —OC 1-6 alkyl;

R 3 is selected from the group consisting of: hydrogen and halogen;

R 4 is hydrogen or C 1-6 alkylO—; or a pharmaceutically acceptable salt thereof

R 5 is —CO 2 R 6 ;

R 6 is selected from the group consisting of: hydrogen and —C 1-6 alkyl, wherein each alkyl is unsubstituted or substituted with one to three substituents selected from R h ; and

or a pharmaceutically acceptable salt thereof.

16. The compound according to claim 1 of structural Formula Ik:

wherein

A is pyrazine, wherein pyrazine is unsubstituted or substituted with one substituent selected from R a ;

B is pyridine, wherein pyridine is unsubstituted or substituted with one to five substituents selected from R b ;

R 1 is —C 1-3 alkyl;

R 2 is cyclopropyl, unsubstituted or substituted with 1-4 substituents selected from C 1-6 alkyl, halogen, and —OC 1-6 alkyl;

R 3 is halogen;

R 4 is hydrogen or C 1-6 alkyl-O—;

R 5 is —CO 2 R 6 ;

R 6 is hydrogen; and

or a pharmaceutically acceptable salt thereof.

17. The compound according to claim 1 selected from:

or a pharmaceutically acceptable salt thereof.

18. The compound according to claim 1 which is:

or a pharmaceutically acceptable salt thereof.

19. The compound according to claim 1 which is:

or a pharmaceutically acceptable salt thereof.

20. The compound according to claim 1 which is:

or a pharmaceutically acceptable salt thereof.

21. The compound according to claim 1 which is:

or a pharmaceutically acceptable salt thereof.

22. The compound according to claim 1 which is:

or a pharmaceutically acceptable salt thereof.

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

24. A method of treating type 2 diabetes mellitus in a patient in need of treatment comprising the administration to the patient of a therapeutically effective amount of a compound of claim 1 , or a pharmaceutically acceptable salt thereof.