[7,6]-fused bicyclic antidiabetic compounds

1. A compound of structural formula I:

or a pharmaceutically acceptable salt thereof; wherein

“a” is a single bond;

T is CH;

U is CR 1 ;

V is CR 2 ;

W is CH;

Q is selected from the group consisting of: —CR 4 R 6 ;

X is selected from the group consisting of: —CR 9 R 9 ;

Y is selected from the group consisting of: —CR 9 R 9 ;

Z is oxygen;

A is selected from the group consisting of:

(1) aryl,

(2) heteroaryl,

(3) C 3-6 cycloalkyl, and

(4) C 2-5 cycloheteroalkyl,

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

B is selected from the group consisting of:

(1) hydrogen,

(2) aryl,

(3) aryl-O—,

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

(5) aryl-C 1-10 alkyl-O—,

(6) C 3-6 cycloalkyl,

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

(8) C 3-6 cycloalkyl-C 1-10 alkyl-O—,

(9) C 3-6 cycloalkenyl,

(10) C 3-6 cycloalkenyl-C 1-10 alkyl-,

(11) C 3-6 cycloalkenyl-C 1-10 alkyl-O—,

(12) C 2-5 cycloheteroalkyl,

(13) C 3-6 cycloheteroalkyl-C 1-10 alkyl-,

(14) C 3-6 cycloheteroalkyl-C 1-10 alkyl-O—,

(15) heteroaryl,

(16) heteroaryl-O—,

(17) heteroaryl-C 1-10 alkyl-, and

(18) heteroaryl-C 1-10 alkyl-O—,

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

R 1 and R 2 are each independently selected from:

(1) a bond,

(2) hydrogen,

(3) halogen,

(4) —OR k ,

(5) —CN,

(6) —C 1-6 alkyl,

(7) —C 3-6 cycloalkyl,

(8) —C 3-6 cycloalkyl-C 1-3 alkyl-,

(9) —C 2-6 cycloheteroalkyl, and

(10) —C 2-6 cycloheteroalkyl-C 1-3 alkyl-,

wherein each alkyl, cycloalkyl and cycloheteroalkyl is unsubstituted or substituted with one to three substituents selected from R L , and wherein one of R 1 and R 2 is substituted with a substituent selected from R 7 ,

or R 1 and R 2 together with the atom(s) to which they are attached form a C 3-6 cycloalkyl ring or a C 2-5 cycloheteroalkyl ring containing 0-2 additional heteroatoms independently selected from oxygen, sulfur and N-Rg, wherein each R 1 and R 2 is unsubstituted or substituted with one to three substituents selected from R L , and wherein one of R 1 and R 2 is substituted with a substituent selected from R 7 ;

R 3 is absent or selected from the group consisting of:

(1) hydrogen,

(2) halogen,

(3) —OR e ,

(4) —CN,

(5) —C 1-6 alkyl,

(6) —C 3-6 cycloalkyl, and

(7) —C 3-6 cycloalkyl-C 1-3 alkyl-,

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

R 4 is selected from the group consisting of:

(1) hydrogen,

(2) halogen,

(3) OR e ,

(4) C 0-5 alkylNR c R d ,

(5) C 1-6 alkyl,

(6) C 1-6 alkyl-O—,

(7) C 3-6 cycloalkyl,

(8) C 3-6 cycloalkyl-O—,

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

(10) C 3-6 cycloalkyl-C 1-10 alkyl-O—,

(11) C 2-5 cycloheteroalkyl,

(12) C 2-5 cycloheteroalkyl-O—,

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

(14) C 2-5 cycloheteroalkyl-C 1-10 alkyl-O—,

(15) aryl,

(16) aryl-O—,

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

(18) heteroaryl,

(19) heteroaryl-O—, and

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

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

R 5 is selected from the group consisting of:

(1) hydrogen,

(2) —C 1-6 alkyl, and

(3) —C 3-6 cycloalkyl,

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

R 6 is selected from the group consisting of:

(1) hydrogen,

(2) —C 1-6 alkyl, and

(3) —C 3-6 cycloalkyl,

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

R 7 is selected from the group consisting of:

(1) —CO 2 R 8 ,

(2) —C 1-6 alkyl-CO 2 R 8 ,

(3) —C 1-6 alkyl-CONHSO 2 R m ,

(4) —C 1-6 alkyl-SO 2 NHCOR m ,

(5) —C 1-6 alkyl-tetrazolyl, and

(6) a cycloheteroalkyl selected from the group consisting of:

R 8 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 j ;

R 9 is selected from the group consisting of:

(1) hydrogen,

(2) —C 1-6 alkyl,

(3) halogen,

(4) —(CH 2 ) 0-5 OH,

(5) —(CH 2 ) 0-5 OC 1-6 alkyl,

(6) —(CH 2 ) 0-5 NR c R d ,

(7) —C 3-6 cycloalkyl, and

(8) aryl-C 1-6 alkyl,

wherein each CH 2 , alkyl, cycloalkyl and aryl is unsubstituted or substituted with one to three substituents selected from R j ;

R a is 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, —S(O) 2 —C 1-4 alky, —CN, —OCHF 2 , —OCF 3 , —CF 3 , and —C 0-6 alkyl-NR c R d ;

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 ) p OC 1-10 alkyl,

(10) —O(CH 2 ) p C 3-6 cycloalkyl,

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

(12) —O(CH 2 ) p C 2-5 cycloheteroalkyl,

(13) —O(CH 2 ) p C 2-5 cyclohereroalkyl-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 ) p NR c S(O) m R e ,

(19) —O(CH 2 ) p S(O) m R e ,

(20) —O(CH 2 ) p S(O) m NR c R d ,

(21) —O(CH 2 ) p NR 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 ) p O—C 3-6 cycloalkyl,

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

(31) —OCF 3 ,

(32) —OCHF 2 ,

(33) —(CH 2 ) p C 3-6 cycloalkyl,

(34) —(CH 2 ) p C 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 alky-,

(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 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;

R i 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;

R j 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) — 2-5 cycloheteroalkyl;

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

(1) hydrogen,

(2) —C 1-6 alkyl,

(3) —C 1-6 alkyl-SO 2 C 1-6 alkyl,

(4) —CF 3 , and

(5) —CHF 2 ,

wherein each alkyl is unsubstituted or substituted with one to three substituents independently selected from: —OH, —OC 1-6 alkyl, halogen, 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 R m is independently selected from the group consisting of:

(1) —C 1-10 alkyl,

(2) —C 2-10 alkenyl,

(3) —C 3-6 cycloalkyl,

(4) —C 3-6 cycloalkyl-C 1-10 alkyl-,

(5) —C 2-5 cycloheteroalkyl,

(6) —C 2-5 cycloheteroalkyl-C 1-10 alkyl-,

(7) aryl,

(8) heteroaryl,

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

(10) heteroaryl-C 1-1 0 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 A is selected from the group consisting of:

(1) aryl,

(2) heteroaryl, and

(3) C 2-5 cycloheteroalkyl,

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

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

(1) phenyl,

(2) pyridyl, and

(3) azetidine,

wherein each phenyl, pyridyl and azetidine is unsubstituted or substituted with one to five substituents 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,

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

(3) heteroaryl,

wherein each alkyl, aryl and 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 selected from the group consisting of:

(1) phenyl,

(2) —CH 2 -phenyl, and

(3) pyridyl,

wherein each phenyl and pyridyl 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 and R 2 are each independently selected from:

(1) hydrogen, and

(2) —C 1-6 alkyl,

wherein each alkyl is unsubstituted or substituted with one to three substituents selected from R L , and wherein one of R 1 and R 2 is substituted with a substituent selected from R 7 ; or a pharmaceutically acceptable salt thereof.

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

(1) hydrogen, and

(2) —C 2 alkyl,

wherein each alkyl is unsubstituted or substituted with one to three substituents selected from R L , and wherein one of R 1 and R 2 is substituted with a substituent selected from R 7 ; or a pharmaceutically acceptable salt thereof.

8. The compound according to claim 1 wherein

R 3 is absent or hydrogen;

R 4 is hydrogen;

R 5 is hydrogen; and

R 6 is hydrogen;

or a pharmaceutically acceptable salt thereof.

9. The compound according to claim 1 wherein R 7 is —CO 2 R 8 ; or a pharmaceutically acceptable salt thereof.

10. The compound according to claim 1 wherein R 8 is hydrogen; or a pharmaceutically acceptable salt thereof.

11. The compound according to claim 1 wherein R 9 is hydrogen; or a pharmaceutically acceptable salt thereof.

12. The compound according to claim 1 of structural Formula Ia:

wherein

“a” is a single bond;

Q is selected from the group consisting of: —CR 4 R 6 ;

X is selected from the group consisting of: —CR 9 R 9 ;

Y is selected from the group consisting of: —CR 9 R 9 ;

Z is oxygen;

A is selected from the group consisting of:

(1) aryl,

(2) heteroaryl, and

(3) C 2-5 cycloheteroalkyl,

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

R 1 and R 2 are each independently selected from:

(1) hydrogen, and

(2) —C 1-6 alkyl,

wherein each alkyl is unsubstituted or substituted with one to three substituents selected from

R L , and wherein one of R 1 and R 2 is substituted with a substituent selected from R 7 ;

R 3 is absent or hydrogen;

R 4 is hydrogen;

R 5 is hydrogen;

R 6 is hydrogen;

R 7 is —CO 2 R 8 ;

R 8 is hydrogen;

R 9 is hydrogen;

each R L is independently selected from the group consisting of: —C 1-10 alkyl, and -C 3-6 cycloalkyl, wherein each alkyl, and cycloalkyl is unsubstituted or substituted with one to four substituents independently selected from C 1-6 alkyl, halogen, and —OC 1-6 alkyl; and

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

or a pharmaceutically acceptable salt thereof.

13. The compound according to claim 1 of structural Formula Ia:

wherein

“a” is a single bond;

Q is selected from the group consisting of: —CR 4 R 6 ;

X is selected from the group consisting of: —CR 9 R 9 ;

Y is selected from the group consisting of: —CR 9 R 9 ;

Z is oxygen;

A is selected from the group consisting of:

(1) phenyl,

(2) pyridyl, and

(3) azetidine,

wherein each phenyl, pyridyl and azetidine is unsubstituted or substituted with one to five substituents selected from R a ;

B is selected from the group consisting of:

(1) phenyl,

(2) —CH 2 -phenyl, and

(3) pyridyl,

wherein each phenyl and pyridyl is unsubstituted or substituted with one to five substituents selected from R b ;

R 1 and R 2 are each independently selected from:

(1) hydrogen, and

(2) —C 2 alkyl,

wherein each alkyl is unsubstituted or substituted with one to three substituents selected from R L , and wherein one of R 1 and R 2 is substituted with a substituent selected from R 7 ;

R 3 is absent or hydrogen;

R 4 is hydrogen;

R 5 is hydrogen;

R 6 is hydrogen;

R 7 is —CO 2 R 8 ;

R 8 is hydrogen;

R 9 is hydrogen;

each R L is independently selected from the group consisting of: —CH 3 , and —cyclopropyl; and

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

or a pharmaceutically acceptable salt thereof.

14. The compound according to claim 13 selected from:

or a pharmaceutically acceptable salt thereof.

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

16. 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.