Antidiabetic bicyclic compounds

1. A compound of structural formula I:

or a pharmaceutically acceptable salt thereof; wherein

A, B, C and D are CH;

T is CH;

U is CH;

V is CH;

W is CH;

X is selected from the group consisting of:

(1) aryl, and

(2) heteroaryl,

wherein aryl and heteroaryl are unsubstituted or substituted with one to three substituents selected from R a ;

Y is oxygen;

Z is selected from the group consisting of: —OH, and —O—C 1-6 alkyl;

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

(1) hydrogen, and

(2) —C 1-6 alkyl,

wherein alkyl is unsubstituted or substituted with one, two or three halogens;

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

(1) —C 1-6 alkyl, and

(2) —C 3-6 cycloalkyl,

wherein alkyl and cycloalkyl are unsubstituted or substituted with one, two or three halogens;

each R 3 is independently selected from the group consisting of:

(1) hydrogen,

(2) halogen,

(3) —(CH 2 ) s —OC 1-6 alkyl,

(4) —(CH 2 ) s —OH,

(5) —CN, and

(6) —C 1-6 alkyl,

wherein alkyl is unsubstituted or substituted with one, two or three substituents selected from halogen, OH, and OC 1-6 alkyl;

each R 4 is independently selected from the group consisting of:

(1) hydrogen,

(2) halogen, and

(3) —C 1-6 alkyl,

wherein alkyl is unsubstituted or substituted with one, two or three substituents selected from halogen, OH, and OC 1-6 alkyl;

each R 5 is independently selected from the group consisting of:

(1) hydrogen,

(2) —C 1-6 alkenyl,

(3) halogen,

(4) —(CH 2 ) t —O—C 1-6 alkyl,

(5) —CN,

(6) aryl,

(7) heteroaryl, and

(8) C 3-6 cycloalkyl,

wherein each alkyl, alkenyl, cycloalkyl, aryl and heteroaryl is unsubstituted or substituted with one, two, or three substituents selected from R b ;

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

(1) —C 1-6 alkyl,

(2) halogen,

(3) —(CH 2 ) u —OC 1-6 alkyl,

(4) —OH, —S(O) u R e ,

(5) —S(O) u NR c R d ,

(6) —CN,

(7) —C(O)NR c R d ,

(8) —CF 3 ,

(9) —OCF 3 , and

(10) —OCHF 2 ,

wherein each alkyl is unsubstituted or substituted with C 1-6 alkyl, halogen, —O—C 1-6 alkyl and —CF 3 ;

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) —C(O)R e ,

(10) —OC(O)R e ,

(11) —CO 2 R e ,

(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) —OCF 3 ,

(17) —OCHF 2 ,

(18) —(CH 2 )vC 3-6 cycloalkyl, and

(19) —(CH 2 )vC 7-5 cycloheteroalkyl,

wherein each CH 2 , alkyl, alkenyl, cycloalkyl, and cycloheteroalkyl is unsubstituted or substituted with —C 1-6 alkyl, halogen, —O—C 1-6 alkyl and —CF 3 ;

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

(1) hydrogen, and

(2) C 1-10 alkyl,

wherein each alkyl is unsubstituted or substituted with one to three substituents selected from C 1-6 alkyl;

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

(1) hydrogen, and

(2) C 1-10 alkyl,

wherein each alkyl is unsubstituted or substituted with one to three substituents selected from C 1-6 alkyl;

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

(1) hydrogen, and

(2) C 1-10 alkyl,

wherein each alkyl is unsubstituted or substituted with one to three substituents selected from C 1-6 alkyl;

each n is independently selected from: 1 and 2;

each m is independently selected from: 1 and 2;

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

each q is independently selected from: 1, 2, 3 and 4;

each r is independently selected from: 1, 2, 3 and 4;

each s is independently selected from: 0, 1, 2, 3 and 4;

each t is independently selected from: 0, 1, 2, 3 and 4;

each u is independently selected from: 0, 1, 2, 3, and 4; and

each v is independently selected from: 0, 1, 2, 3 and 4.

2. The compound according to claim 1 wherein X is aryl, wherein aryl is unsubstituted or substituted with one to three substituents selected from R a ; or a pharmaceutically acceptable salt thereof.

3. The compound according to claim 1 wherein Z is —OH; or a pharmaceutically acceptable salt thereof.

4. The compound according to claim 1 wherein R 2 is —C 3-6 cycloalkyl, wherein cycloalkyl is unsubstituted or substituted with one, two or three halogens; or a pharmaceutically acceptable salt thereof.

5. The compound according to claim 1 wherein each R 3 is independently selected from the group consisting of:

(1) hydrogen, and

(2) halogen;

or a pharmaceutically acceptable salt thereof.

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

7. The compound according to claim 1 wherein each R 5 is independently selected from the group consisting of:

(1) hydrogen,

(2) halogen, and

(3) heteroaryl,

wherein each heteroaryl is unsubstituted or substituted with one, two, or three substituents selected from R b ; or a pharmaceutically acceptable salt thereof.

8. The compound according to claim 1 wherein

A, B, C and D are CH;

T is CH;

U is CH;

V is CH;

W is CH;

X is selected from the group consisting of:

(1) aryl, and

(2) heteroaryl,

wherein aryl and heteroaryl are unsubstituted or substituted with one to three substituents selected from R a ;

Y is oxygen;

Z is selected from the group consisting of: —OH, and —O—C 1-6 alkyl;

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

(1) hydrogen, and

(2) —C 1-6 alkyl,

wherein alkyl is unsubstituted or substituted with one, two or three halogens;

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

(1) —C 1-6 alkyl, and

(2) —C 3-6 cycloalkyl,

wherein alkyl and cycloalkyl are unsubstituted or substituted with one, two or three halogens;

each R 3 is independently selected from the group consisting of:

(1) hydrogen, and

(2) halogen;

R 4 is hydrogen;

each R 5 is independently selected from the group consisting of:

(1) hydrogen,

(2) —C 1-6 alkenyl,

(3) halogen,

(4) —(CH 2 ) t —O—C 1-6 alkyl,

(5) —CN,

(6) aryl,

(7) heteroaryl, and

(8) —C 3-6 cycloalkyl,

wherein each alkyl, alkenyl, cycloalkyl, aryl and heteroaryl is unsubstituted or substituted with one, two, or three substituents selected from R b ;

or a pharmaceutically acceptable salt thereof.

9. The compound according to claim 1 wherein

A, B, C and D are CH;

T is CH;

U is CH;

V is CH;

W is CH;

X is aryl, wherein aryl is unsubstituted or substituted with one to three substituents selected from R a ;

Y is oxygen;

Z is —OH;

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

(1) hydrogen, and

(2) —C 1-6 alkyl,

wherein alkyl is unsubstituted or substituted with one, two or three halogens;

R 2 is —C 3-6 cycloalkyl, wherein cycloalkyl is unsubstituted or substituted with one, two or three halogens;

each R 3 is independently selected from the group consisting of:

(1) hydrogen, and

(2) halogen;

R 4 is hydrogen; and

each R 5 is independently selected from the group consisting of:

(1) hydrogen,

(2) halogen, and

(3) heteroaryl,

wherein each heteroaryl is unsubstituted or substituted with one, two, or three substituents selected from R b ;

or a pharmaceutically acceptable salt thereof.

10. The compound according to claim 9 selected from:

and pharmaceutically acceptable salts thereof.

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

12. A pharmaceutical composition comprising

(1) a compound of claim 1 or a pharmaceutically acceptable salt thereof;

(2) one or more compounds selected from the group consisting of:

(a) PPAR gamma agonists and partial agonists;

(b) biguanides;

(c) protein tyrosine phosphatase-1B (PTP-1B) inhibitors;

(d) dipeptidyl peptidase IV (DP-IV) inhibitors;

(e) insulin or an insulin mimetic;

(f) sulfonylureas;

(g) α-glucosidase inhibitors;

(h) agents which improve a patient's lipid profile, said agents being selected from the group consisting of (i) HMG-CoA reductase inhibitors, (ii) bile acid sequestrants, (iii) nicotinyl alcohol, nicotinic acid or a salt thereof, (iv) PPARα agonists, (v) cholesterol absorption inhibitors, (vi) acyl CoA: cholesterol acyltransferase (ACAT) inhibitors, (vii) CETP inhibitors, and (viii) phenolic anti-oxidants;

(i) PPARα/γ dual agonists,

(j) PPARδ agonists,

(k) antiobesity compounds,

(l) ileal bile acid transporter inhibitors;

(m) anti-inflammatory agents;

(n) glucagon receptor antagonists;

(o) GLP-1;

(p) GIP-1;

(q) GLP-1 analogs;

(r) HSD-1 inhibitors;

(s) SGLT 1 inhibitors; and

(t) SGLT 2 inhibitors; and

(3) a pharmaceutically acceptable carrier.

13. A pharmaceutical composition comprising a compound according to claim 1 , or a pharmaceutically acceptable salt thereof, and a compound selected from simvastatin, ezetimibe and sitagliptin; and a pharmaceutically acceptable carrier.