Azabenzimidazole tetrahydropyran 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 selected from:

(1) —S—,

(2) —O—, and

(3) —NH—;

Y is selected from:

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

Z is NR 5 ;

each R 1 is independently selected from:

(1) phenyl,

(2) phenyl-pyrrolidine,

(3) biphenyl, and

(4) phenyl-pyridine,

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

R 2 is selected from halogen;

R 4 is selected from

(1) hydrogen,

(2) halogen, and

(3) —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) F,

(2) oxo,

(3) —OH,

(4) —CH 2 OH,

(5) —C(CH 3 ) 2 CH 2 OH,

(6) —C(CH 3 ) 2 OH,

(7) —CF 2 C(CH 3 ) 2 OH,

(8) —CH 2 C(CH 3 ) 2 OH,

(9) —CH(CF 3 )NH-cyclopropyl,

(10) —NHCO 2 CH 3 ,

(11) —CN,

(12) —CH 2 F,

(13) —CH 2 CF 3 ,

(14) —CH(NH 2 )CF 3 ,

(15) —NHCO 2 CH 2 CH(OH)CH 2 OH,

(16) —NHCO 2 (CH 2 ) 2 -imidazole,

(17) —NHCO 2 (CH 2 ) 2 -morpholine,

(18) —NHCO 2 (CH 2 ) 2 N(CH 3 ) 2 ,

(20) —OCH(CH 3 )CH 2 OH,

(21) —O-cyclobutyl,

(22) —O-oxetane,

(23) —O-tetrahydrothiopyran,

(24) —SO 2 CH 3 ,

(25) —CH 2 SO 2 CH 3 ,

(26) —(CH 2 ) 2 SO 2 CH 3 ,

(27) —SO 2 (CH 2 ) 2 CH 3 ,

(28) —SO 2 CH(CH 3 ) 2 ,

(29) —SO 2 CH 2 CH(CH 3 ) 2 ,

(30) —SO 2 CH 2 C(CH 3 ) 2 OH,

(31) —SO 2 -cyclopropyl,

(32) —SO 2 -cyclopentyl,

(33) —SO 2 -oxetane,

(34) —SO 2 CH 2 -oxetane,

(35) —SO 2 -azetidine,

(36) —SO 2 -piperidine,

(37) —SO 2 NH 2 ,

(38) —SO 2 NH(CH 2 ) 2 OH,

(39) —SO 2 NH(CH 2 ) 2 N(CH 3 ) 2 ,

(40) —SO 2 NH-cyclopropyl,

(41) —NHCH(CH 3 )(CH 2 ) 2 SO 2 CH 3 ,

(42) —C(O)pyrrolidine,

(43) —C(O)piperidine,

(44) —C(O)NHCH 3 ,

(45) —CH 2 CH(NH 2 )CO 2 H,

(46) —(CH 2 ) 3 CO 2 H,

(47) —CO 2 CH 3 ,

(48) —CO 2 CH(CH 3 ) 2 ,

(49) —CH(CF 3 )morpholine,

(50) pyrrolidine,

(51) pyrazole,

(52) triazole,

(53) pyrimidine,

(54) imidazole,

(55) oxadiazole, and

(56) oxazole;

each R b is independently selected from:

(1) —C 1-6 alkyl, and

(2) —(CH 2 )s-OH,

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 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 , and

(8) —C 1-6 alkyl-OH;

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 R j 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 is independently selected from:

(1) pyrrolidine,

(2) piperidine,

(3) —(CH 2 ) 2 -imidazole, and

(4) —(CH 2 ) 2 -morpholine,

wherein each cycloheteroalkyl 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, and —CO 2 C 1-6 alkyl;

each R i is independently selected from C 1-6 alkyl;

r is 0, 1 or 2;

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

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

2. The compound according to claim 1 , wherein X is —O—; or a pharmaceutically acceptable salt thereof.

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

wherein Y is substituted with 1, 2, 3, 4 or 5 substituents selected from R b ; or a pharmaceutically acceptable salt thereof.

4. 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.

5. The compound according to claim 1 , wherein each R 1 is independently selected from:

(1) phenyl,

(2) phenyl-pyrrolidine, and

(3) phenyl-pyridine,

wherein each pyrrolidine, phenyl, and pyridine is unsubstituted or 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 4 is hydrogen; and R 5 is hydrogen; or a pharmaceutically acceptable salt thereof.

7. A compound selected from:

or a pharmaceutically acceptable salt thereof.

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

9. 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.

10. A compound selected from:

or a pharmaceutically acceptable salt thereof.