Antidiabetic bicyclic compounds

1. A compound of structural formula I:

or a pharmaceutically acceptable salt thereof; wherein

“a” is a single bond or a double bond, provided that if “a” is a double bond, then R 5 and R 6b are absent;

T is CH;

U is CR 1 ;

V is CR 2 ;

W is CH;

X is selected from the group consisting of:

(1) oxygen,

(2) sulfur,

(3) S(O) 2 ,

(4) —CR g R g , and

(5) C═O;

Y is selected from the group consisting of:

(1) oxygen, and

(2) —CR 4a R 4b ,

provided that if X is oxygen, or sulfur, then Y is not oxygen, and further provided that if X is S(O) 2 , then Y is not oxygen;

A is selected from the group consisting of:

(1) aryl, and

(2) C 3-5 cycloheteroalkyl,

wherein each aryl and cycloheteroalkyl is unsubstituted or substituted with one to five substituents independently selected from R a ;

B is selected from the group consisting of:

(1) aryl,

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

(3) heteroaryl,

wherein each alkyl, aryl and heteroaryl is unsubstituted or substituted with one to five substituents independently selected from R b ;

R 1 and R 2 are each independently selected from:

(1) hydrogen, and

(2) —C 1-6 alkyl,

wherein one of R 1 and R 2 is —C 1-6 alkyl substituted with R 7 , and wherein alkyl is unsubstituted or further substituted with one to three substituents independently selected from R L ;

R 3 is absent or hydrogen;

R 4a is hydrogen;

R 4b is hydrogen;

R 5 is absent or hydrogen;

R 6a is hydrogen;

R 6b is absent or hydrogen;

R 7 is —CO 2 R 8 ;

R 8 is hydrogen;

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

(1) —C 1-6 alkyl,

(2) halogen,

(3) —C 0-6 alkyl-OR e ,

(4) —C 0-6 alkyl-NR c S(O) n R e ,

(5) —C 0-6 alkyl-S(O) n R e ,

(6) —C 0-6 alkyl-S(O) n NR c R d ,

(7) —C 0-6 alkyl-NR c R d ,

(8) —C 0-6 alkyl-C(O)R e ,

(9) —C 0-6 alkyl-OC(O)R e ,

(10) —C 0-6 alkyl-CO 2 R e ,

(11) —C 0-6 alkyl-CN,

(12) —C 0-6 alkyl-C(O)NR c R d ,

(13) —C 0-6 alkyl-NR c C(O)R e ,

(14) —C 0-6 alkyl-NR c C(O)OR e ,

(15) —C 0-6 alkyl-NR c C(O)NR c R d ,

(16) —CF 3 ,

(17) —OCF 3 ,

(18) —OCHF 2 ,

(19) —C 0-6 alkyl-aryl,

(20) —C 0-6 alkyl-heteroaryl,

(21) —C 0-6 alkyl-C 3-10 cycloalkyl,

(22) —C 0-6 alkyl-C 3-10 cycloalkenyl, and

(23) —C 0-6 alkyl-C 2-10 cycloheteroalkyl,

wherein each alkyl, cycloalkyl, cycloalkenyl, cycloheteroalkyl, aryl and heteroaryl is unsubstituted or substituted with one to five substituents independently selected from: —C 1-6 alkyl, halogen, OH, —O—C 1-6 alkyl, —CN, —OCHF 2 , —OCF 3 , —CF 3 , and —C 0-6 alkyl-NR c R d ;

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

(1) —C 1-10 alkyl,

(2) —C 2-10 alkenyl,

(3) —CF 3 ,

(4) halogen,

(5) —CN,

(6) —OH,

(7) —OC 1-10 alkyl,

(8) —OC 2-10 alkenyl,

(9) —O(CH 2 )pOC 1-10 alkyl,

(10) —O(CH 2 )pC 3-6 cycloalkyl,

(11) —O(CH 2 )pC 3-6 cycloalkyl-C 1-10 alkyl,

(12) —O(CH 2 )pC 2-5 cycloheteroalkyl,

(13) —O(CH 2 )pC 2-5 cycloheteroalkyl-C 1-10 alkyl,

(14) —O-aryl,

(15) —O-heteroaryl,

(16) —O-aryl-C 1-10 alkyl,

(17) —O-heteroaryl-C 1-10 alkyl,

(18) —O(CH 2 )pNR c S(O) m R e ,

(19) —O(CH 2 )pS(O) m R e ,

(20) —O(CH 2 )pS(O) m NR c R d ,

(21) —O(CH 2 )pNR c R d ,

(22) —C(O)R e ,

(23) —OC(O)R e ,

(24) —CO 2 R e ,

(25) —C(O)NR c R d ,

(26) —NR c C(O)R e ,

(27) —NR c C(O)OR e ,

(28) —NR c C(O)NR c R d ,

(29) —O(CH 2 )pO—C 3-6 cycloalkyl,

(30) —O(CH 2 )pO—C 2-5 cycloheteroalkyl,

(31) —OCF 3 ,

(32) —OCHF 2 ,

(33) —(CH 2 )pC 3-6 cycloalkyl,

(34) —(CH 2 )pC 2-5 cycloheteroalkyl,

(35) aryl,

(36) heteroaryl,

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

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

wherein each CH, CH 2 , alkyl, alkenyl, cycloalkyl, cycloheteroalkyl, aryl and heteroaryl is unsubstituted or substituted with one to five substituents independently selected from: —C 1-6 alkyl, halogen, OH, —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 2-10 alkenyl,

(4) C 3-6 cycloalkyl,

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

(6) C 2-5 cycloheteroalkyl,

(7) C 2-5 cycloheteroalkyl-C 1-10 alkyl-,

(8) aryl,

(9) heteroaryl,

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

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

wherein each alkyl, alkenyl, 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 2-10 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 2-10 alkenyl,

(4) —C 3-6 cycloalkyl,

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

(6) —C 2-5 cycloheteroalkyl,

(7) C 2-5 cycloheteroalkyl-C 1-10 alkyl-,

(8) aryl,

(9) aryl-C 1-10 alkyl-,

(10) heteroaryl, and

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

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

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, C 1-6 alkyl, cyano and S(O) 2 C 1-6 alkyl;

each R g is selected from the group consisting of:

(1) hydrogen,

(2) —C(O)R e , and

(3) —C 1-10 alkyl,

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

each R h 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, C 1-6 alkyl, cyano and S(O) 2 C 1-6 alkyl;

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

(1) —CO 2 C 1-6 alkyl,

(2) —C 1-10 alkyl,

(3) —C 2-10 alkenyl,

(4) —C 2-10 alkynyl,

(5) —C 3-6 cycloalkyl,

(6) —C 2-6 cycloheteroalkyl,

(7) aryl, and

(8) heteroaryl,

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

each n is independently selected from: 0, 1 or 2;

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

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

each r is independently selected from: 0, 1, 2 or 3.

2. The compound according to claim 1 wherein X is selected from the group consisting of:

(1) oxygen,

(2) sulfur, and

(3) —CR g R g ;

or a pharmaceutically acceptable salt thereof.

3. The compound according to claim 1 wherein A is aryl, wherein aryl is unsubstituted or substituted with one to five substituents independently selected from R a ; or a pharmaceutically acceptable salt thereof.

4. The compound according to claim 1 wherein B is selected from the group consisting of:

(1) aryl, and

(2) heteroaryl,

wherein each aryl and heteroaryl is unsubstituted or substituted with one to five substituents independently selected from R b ; or a pharmaceutically acceptable salt thereof.

5. The compound according to claim 1 wherein R 1 and R 2 are each independently selected from:

(1) hydrogen, and

(2) ethyl,

wherein one of R 1 and R 2 is ethyl substituted with R 7 , and wherein ethyl is unsubstituted or further substituted with one to three substituents independently selected from R L ;

or a pharmaceutically acceptable salt thereof.

6. The compound according to claim 1 wherein

“a” is a single bond or a double bond, provided that if “a” is a double bond, then R 5 and R 6b are absent;

T is CH;

U is CR 1 ;

V is CR 2 ;

W is CH;

X is selected from the group consisting of:

(1) oxygen,

(2) sulfur,

(3) S(O) 2 ,

(4) —CR g R g , and

(5) C═O;

Y is selected from the group consisting of:

(1) oxygen, and

(2) —CR 4a R 4b ,

provided that if X is oxygen or sulfur, then Y is not oxygen, and further provided that if X is S(O) 2 , then Y is not oxygen;

A is selected from the group consisting of:

(1) aryl, and

(2) C 3-5 cycloheteroalkyl,

wherein each aryl and cycloheteroalkyl is unsubstituted or substituted with one to five substituents independently selected from R a ;

B is selected from the group consisting of:

(1) aryl,

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

(3) heteroaryl,

wherein each alkyl, aryl and heteroaryl is unsubstituted or substituted with one to five substituents independently selected from R b ;

R 1 and R 2 are each independently selected from:

(1) hydrogen, and

(2) —C 1-6 alkyl,

wherein one of R 1 and R 2 is —C 1-6 alkyl substituted with R 7 , and wherein alkyl is unsubstituted or further substituted with one to three substituents independently selected from R L ;

R 3 is absent or hydrogen;

R 4a is hydrogen;

R 4b is hydrogen;

R 5 is absent or hydrogen;

R 6a is hydrogen; and

R 6b is absent or hydrogen;

R 7 is —CO 2 R 8 ;

R 8 is hydrogen;

R a is halogen;

each R b is independently selected from the group consisting of: —C 1-10 alkyl, —CF 3 , halogen, —OC 1-10 alkyl, and —OC 3-6 cycloalkyl;

R g is hydrogen; and

each R L is independently selected from the group consisting of: —C 1-10 alkyl, and —C 3-6 cycloalkyl;

or a pharmaceutically acceptable salt thereof.

7. The compound according to claim 1 wherein

“a” is a single bond or a double bond, provided that if “a” is a double bond, then R 5 and R 6b are absent;

T is CH;

U is CR 1 ;

V is CH;

W is CH;

X is selected from the group consisting of:

(1) oxygen,

(2) sulfur, and

(3) —CR g R g ;

Y is selected from the group consisting of:

(1) oxygen, and

(2) —CH 2 ,

provided that if X is oxygen or sulfur, then Y is not oxygen;

A is aryl, wherein aryl is unsubstituted or substituted with one to five substituents independently selected from R a ;

B is selected from the group consisting of:

(1) aryl, and

(2) heteroaryl,

wherein each aryl and heteroaryl is unsubstituted or substituted with one to five substituents independently selected from R b ;

R 1 is ethyl, wherein ethyl is unsubstituted or substituted with one to three substituents independently selected from R L , and wherein R 1 is further substituted with R 7 ;

R 3 is absent or hydrogen;

R 4a is hydrogen;

R 4b is hydrogen;

R 5 is absent or hydrogen;

R 6a is hydrogen; and

R 6b is absent or hydrogen;

R 7 is —CO 2 R 8 ;

R 8 is hydrogen;

R a is halogen;

each R b is independently selected from the group consisting of: halogen, and —OC 1-10 alkyl;

R g is hydrogen; and

each R L is independently selected from the group consisting of: —C 1-10 alkyl, and —C 3-6 cycloalkyl;

or a pharmaceutically acceptable salt thereof.

8. The compound according to claim 7 selected from:

or a pharmaceutically acceptable salt thereof.

9. The compound according to claim 1 selected from:

or a pharmaceutically acceptable salt thereof.

10. The compound according to claim 1 selected from:

or a pharmaceutically acceptable salt thereof.

11. The compound according to claim 1 selected from:

or a pharmaceutically acceptable salt thereof.

12. The compound according to claim 1 selected from:

or a pharmaceutically acceptable salt thereof.

13. The compound according to claim 1 selected from:

or a pharmaceutically acceptable salt thereof.

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

15. 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.