Azabenzimidazole tetrahydrofuran derivatives

1. A compound of structural formula I:

or a pharmaceutically acceptable salt thereof, wherein:

T is N;

U is —CR 1 —;

V is —CR 2 —;

W is —CR 4 —;

X is —O—;

Y is selected from:

wherein Y is unsubstituted or substituted with 1, 2, 3, 4 or 5 substituents selected from R b ;

Z is NR 5 ;

each R1 is independently selected from:

(1) —(CH 2 ) p aryl-aryl, and

(2) —(CH 2 ) p aryl-heteroaryl,

wherein each CH 2 is unsubstituted or substituted with 1 or 2 substituents selected from: halogen, CF 3 , —OH, —NH 2 , C 1-6 alkyl, —OC 1-6 alkyl, NHC 1-6 alkyl, and —N(C 1-6 alkyl) 2 , and wherein each aryl and heteroaryl is unsubstituted or substituted with 1, 2, 3 or 4 substituents independently selected from R a , provided that when Y is:

and R 1 is biphenyl, then R 1 is substituted with 1, 2, 3 or 4 substituents independently selected from R a ;

R 2 is selected from halogen;

R 4 is selected from hydrogen, halogen, and —C 1-6 alkyl;

R 5 is selected from:

(1) hydrogen,

(2) —C 1-6 alkyl,

(3) —C 1-6 alkenyl,

(4) —(CH 2 ) u OH,

(5) —CH 2 CO 2 H, and

(6) —CH 2 CO 2 C 1-6 alkyl;

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

(1) halogen,

(2) —(CH 2 ) m OH,

(3) —C(O)R f ,

(4) —C 2-6 cycloheteroalkyl,

(5) —SO 2 —C 3-7 cycloalkyl, and

(6) -heteroaryl,

wherein each CH 2 is unsubstituted or substituted with 1 or 2 substituents selected from: oxo, —OH, —(CH 2 ) 1-3 OH, —CN, —NH 2 , —NH(C 1-6 alkyl), —N(C 1-6 alkyl) 2 , oxo, —C 1-6 alkyl, —C 1-6 alkyl substituted with 1-5 OH, —OC 1-6 alkyl, halogen, —CH 2 F, —CHF 2 , —CF 3 , —CO 2 H, and —CO 2 C 1-6 alkyl, and wherein cycloheteroalkyl and heteroaryl are unsubstituted or substituted with 1, 2, 3 or 4 substituents selected from: oxo, —OH, —(CH 2 ) 1-5 OH, —(CH 2 ) 1-5 CN, —CN, —NH 2 , —NH(C 1-6 alkyl), —N(C 1-6 alkyl) 2 , —C 1-6 alkyl substituted with 1-5 OH, —OC 1-6 alkyl, halogen, —CH 2 F, —CHF 2 , —CF 3 , —(CH 2 ) 1-5 CF 3 optionally substituted with 1, 2 or 3 —OH, —CO 2 H, —CO 2 C 1-6 alkyl, and —SO 2 C 1-6 alkyl;

each R b is independently selected from:

(1) hydrogen,

(2) —C 1-6 alkyl,

(3) —C 1-6 alkenyl,

(4) —(CH 2 ) n —C 3-10 cycloalkyl,

(5) —(CH 2 ) n —C 3-10 cycloalkenyl,

(6) —(CH 2 ) n —C 2-10 cycloheteroalkyl,

(7) —(CH 2 ) n —C 2-10 cycloheteroalkenyl,

(8) —(CH 2 ) n -aryl,

(9) —(CH 2 ) n -heteroaryl,

(10) oxo,

(11) —(CH 2 ) n —CF 3 ,

(12) —(CH 2 ) n —CN,

(13) —(CH 2 ) t -halogen,

(14) —(CH 2 ) s —OH,

(15) —(CH 2 ) n —NO 2 ,

(16) —(CH 2 ) n —NH 2 ,

(17) —(CH 2 ) n —NH(C 1-6 alkyl),

(18) —(CH 2 ) n —N(C 1-6 alkyl) 2 ,

(19) —(CH 2 ) n —NHCO 2 H,

(20) —(CH 2 ) n —OC 1-6 alkyl,

(21) —(CH 2 ) n —OC 1-6 alkenyl,

(22) —(CH 2 ) n —COC 1-6 alkyl,

(23) —(CH 2 ) n —CO 2 H,

(24) —(CH 2 ) n —OCOH,

(25) —(CH 2 ) n —CO 2 R i ,

(26) —(CH 2 ) n —OC(O)R i ,

(27) —(CH 2 ) q C(O)N(R e ) 2 ,

(28) —(CH 2 ) q CO 2 N(R e ) 2 ,

(29) —(CH 2 ) n C(O)(CH 2 ) n N(R g ) 2 ,

(30) —(CH 2 ) n OC(O)(CH 2 ) n N(R g ) 2 ,

(31) —(CH 2 ) n N(R e )C(O)C 1-6 alkyl,

(32) —(CH 2 ) n N(R e )SO 2 R i ,

(33) —(CH 2 ) n SO 2 C 1-6 alkyl,

(34) —(CH 2 ) n SO 2 N(R e )R g ,

(35) —(CH 2 ) n SO 2 N(R e )C(O)R i ,

(36) —(CH 2 ) n SO 2 N(R e )CO 2 R i ,

(37) —(CH 2 ) n SO 2 N(R e )CON(R g ) 2 ,

(38) —(CH 2 ) n C(O)N(R e )SO 2 R i ,

(39) —(CH 2 ) n N(R e )C(O)N(R g ) 2 ,

(40) ═N(OH), and

(41) ═N(OC 1-6 alkyl),

wherein each CH 2 is unsubstituted or substituted with 1 or 2 substituents selected from: —C 1-6 alkyl, —OH, halogen and —NH 2 wherein each NH is unsubstituted or substituted with 1 substituent selected from R c , and wherein each alkyl, cycloalkyl, cycloalkenyl, cycloheteroalkyl, cycloheteroalkenyl, aryl and heteroaryl is unsubstituted or substituted with 1, 2, 3 or 4 substituents selected from R c ;

each R c is independently selected from:

(1) halogen,

(2) oxo,

(3) —(CH 2 ) r OH,

(4) —(CH 2 ) r N(R e ) 2 ,

(5) —(CH 2 ) r CN,

(6) —C 1-6 alkyl,

(7) —CF 3 ,

(8) —C 1-6 alkyl-OH,

(9) —OCH 2 OC 1-6 alkyl,

(10) —(CH 2 ) r OC 1-6 alkyl,

(11) —OCH 2 aryl,

(12) —(CH 2 ) r SC 1-6 alkyl,

(13) —(CH 2 ) r C(O)R f ,

(14) —(CH 2 ) r C(O)N(R e ) 2 ,

(15) —(CH 2 ) r CO 2 H,

(16) —(CH 2 ) r CO 2 R f ,

(17) —(CH 2 ) r C 3-7 cycloalkyl,

(18) —(CH 2 ) r C 2-6 cycloheteroalkyl,

(19) —(CH 2 ) r aryl, and

(20) —(CH 2 ) r heteroaryl,

wherein each CH 2 is unsubstituted or substituted with 1 or 2 substituents selected from: oxo, —OH, —CN, —N(R h ) 2 , —OC 1-6 alkyl, halogen, —CH 2 F, —CHF 2 , —CF 3 , —CO 2 H, —CO 2 C 1-6 alkyl, —C 3-7 cycloalkyl and heteroaryl, and wherein alkyl, cycloalkyl, cycloheteroalkyl, aryl and heteroaryl are unsubstituted or substituted with 1, 2, 3 or 4 substituents selected from: oxo, —OH, —CN, —N(R h ) 2 , —C 1-6 alkyl, —OC 1-6 alkyl, halogen, —CH 2 F, —CHF 2 , —CF 3 , —CO 2 H, —CO 2 C 1-6 alkyl, —C 3-7 cycloalkyl and heteroaryl;

each R e , R g and R h is independently selected from:

(1) hydrogen,

(2) —C 1-6 alkyl, and

(3) —O—C 1-6 alkyl,

wherein alkyl is unsubstituted or substituted with 1, 2, 3 or 4 substituents selected from: —OH, oxo, halogen, C 1-6 alkyl, —OC 1-6 alkyl, —NH 2 , —NH(C 1-6 alkyl), and —N(C 1-6 alkyl) 2 ;

each Rj is independently selected from:

(1) hydrogen,

(2) C 1-6 alkyl,

(3) C 3-6 cycloalkyl,

(4) —C(O)R i ,

(5) —CO 2 R i , and

(6) —SO 2 R i ,

wherein alkyl and cycloalkyl are unsubstituted or substituted with 1, 2, 3 or 4 substituents selected from: —OH, oxo, halogen, C 1-6 alkyl, —OC 1-6 alkyl, —NH 2 , —NH(C 1-6 alkyl), and —N(C 1-6 alkyl) 2 ;

each R f and R i is independently selected from:

(1) C 1-6 alkyl,

(2) —(CH 2 ) r C 4-7 cycloalkyl,

(3) —(CH 2 ) r C 4-7 cycloalkenyl,

(4) —(CH 2 ) r C 3-7 cycloheteroalkyl,

(5) —(CH 2 ) r C 3-7 cycloheteroalkenyl,

(6) —(CH 2 ) r aryl, and

(7) —(CH 2 ) r heteroaryl,

wherein alkyl, cycloalkyl, cycloalkenyl, cycloheteroalkyl, cycloheteroalkenyl, aryl and heteroaryl are unsubstituted or substituted with 1, 2, 3 or 4 substituents selected from: oxo, —OH, —CN, —NH 2 , —NH(C 1-6 alkyl), —N(C 1-6 alkyl) 2 , —C 1-6 alkyl, —OC 1-6 alkyl, halogen, —CH 2 F, —CHF 2 , —CF 3 , —CO 2 H, —CO 2 C 1-6 alkyl, —C 3-7 cycloalkyl, and heteroaryl;

n is 0, 1, 2, 3 or 4;

m is 0, 1, 2, 3 or 4;

p is 0, 1, 2, or 3;

q is 0, 1, 2, 3 or 4;

r is 0, 1 or 2;

s is 0, 1, 2, 3 or 4;

t is 0, 1, 2, 3 or 4; and

u is 0, 1, 2, 3 or 4.

2. The compound according to claim 1 , wherein Y is selected from:

wherein Y is substituted with 1, 2, 3, 4 or 5 substituents selected from R b ; or

a pharmaceutically acceptable salt thereof.

3. The compound according to claim 1 , wherein Y is:

wherein Y is unsubstituted or substituted with 1, 2 or 3 substituents selected from R b ; or a pharmaceutically acceptable salt thereof.

4. The compound according to claim 1 , wherein

each R 1 is independently selected from:

(1) biphenyl,

(2) phenyl-naphthalene,

(3) phenyl-pyridine, and

(4) phenyl-dihydropyrrolopyrazole,

wherein each phenyl, naphthalene, pyridine and dihydropyrrolopyrazole is unsubstituted or substituted with 1, 2, 3 or 4 substituents independently selected from R a , and wherein each biphenyl is substituted with 1, 2, 3 or 4 substituents independently selected from R a ; and

R 2 is selected from halogen;

or a pharmaceutically acceptable salt thereof.

5. The compound according to claim 1 , wherein

R 1 is biphenyl, wherein each phenyl is substituted with 1, 2, 3 or 4 substituents independently selected from R a ; and

R 2 is halogen;

or a pharmaceutically acceptable salt thereof.

6. The compound according to claim 1 , wherein

R 3 is hydrogen or absent; R 4 is hydrogen; and R 5 is hydrogen; or a pharmaceutically acceptable salt thereof.

7. The compound according to claim 1 , wherein

R 3 is hydrogen or absent; R 4 is hydrogen; R 5 is hydrogen; and R 2 is halogen; or a pharmaceutically acceptable salt thereof.

8. The compound according to claim 1 wherein:

T is N;

U is —CR 1 —;

V is —CR 2 —;

W is —CR 4 —;

X is —O—;

Y is selected from:

wherein Y is unsubstituted or substituted with 1, 2, 3, 4 or 5 substituents selected from R b ;

Z is NR 5 ;

R 2 is halogen;

R 4 is hydrogen;

R 5 is hydrogen;

or a pharmaceutically acceptable salt thereof.

9. The compound according to claim 1 wherein:

T is N;

U is —CR 1 —;

V is —CR 2 —;

W is —CR 4 —;

X is —O—;

Y is:

wherein Y is unsubstituted or substituted with 1, 2 or 3 substituents selected from R b ;

Z is NR 5 ;

R 2 is halogen;

R 4 is hydrogen; and

R 5 is hydrogen;

or a pharmaceutically acceptable salt thereof.

10. A compound selected from:

and pharmaceutically acceptable salts thereof.

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

12. A 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.

13. The compound of claim 1 wherein each R a is independently selected from the group consisting of:

(1) —(CH 2 ) m OH,

(2) —C(O)R f ,

(3) —C 2-6 cycloheteroalkyl,

(4) —SO 2 —C 3-7 cycloalkyl, and

(5) -heteroaryl,

wherein each CH 2 is unsubstituted or substituted with 1 or 2 substituents selected from: oxo, —OH, —(CH 2 ) 1-3 OH, —CN, —NH 2 , —NH(C 1-6 alkyl), —N(C 1-6 alkyl) 2 , oxo, —C 1-6 alkyl, —C 1 -6alkyl substituted with 1-5 OH, —OC 1-6 alkyl, halogen, —CH 2 F, —CHF 2 , —CF 3 , —CO 2 H, and —CO 2 C 1-6 alkyl, and wherein cycloheteroalkyl and heteroaryl are unsubstituted or substituted with 1, 2, 3 or 4 substituents selected from: oxo, —OH, —(CH 2 ) 1-5 OH, —(CH 2 ) 1-5 CN, —CN, —NH 2 , —NH(C 1-6 alkyl), —N(C 1-6 alkyl) 2 , —C 1-6 alkyl, —C 1-6 alkyl substituted with 1-5 OH, —OC 1-6 alkyl, halogen, —CH 2 F, —CHF 2 , —CF 3 , —(CH 2 ) 1-5 CF 3 optionally substituted with 1, 2 or 3 —OH, —CO 2 H, —CO 2 C 1-6 alkyl, and —SO 2 C 1-6 alkyl; or a pharmaceutically acceptable salt thereof.

14. A The compound according to claim 1 selected from:

or a pharmaceutically acceptable salt thereof.

15. A compound selected from:

or a pharmaceutically acceptable salt thereof.