Cyclic azabenzimidazole derivatives useful as anti-diabetic agents

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) —O—, and

(2) —O—CH 2 —;

Y is selected from:

(1) C 3-l0 cycloalkyl,

(2) C 3-l0 cycloalkenyl,

(3) C 2-10 cycloheteroalkyl,

(4) C 2-10 cycloheteroalkenyl,

(5) aryl, and

(6) heteroaryl,

wherein cycloalkyl, cycloalkenyl, cycloheteroalkyl, cycloheteroalkenyl, aryl and heteroaryl are unsubstituted or substituted with 1, 2, 3 or 4 substituents selected from R b ;

Z is selected from:

(1) oxo,

(2) —CF 3 ,

(3) —C 1-6 alkyl,

(4) —(CH 2 ) t -halogen,

(5) —(CH 2 ) n CO 2 H,

(6) —(CH 2 ) n OH, and

(7) —(CH 2 ) n SO 2 C 1-6 alkyl,

wherein each CH 2 is unsubstituted or substituted with 1 or 2 substituents selected from C 1-6 alkyl, —OH and —NH 2 ,and wherein each alkyl is unsubstituted or substituted with 1, 2, 3 or 4 substituents selected from R c ;

each R 1 and R 2 is independently selected from:

(1) hydrogen,

(2) halogen,

(3) CN,

(4) CF 3 ,

(5) —C 1-6 alkyl,

(6) —C 2-6 alkenyl,

(7) —C 2-6 alkynyl,

(8) —(CH 2 ) p C 3-10 cycloalkyl,

(9) —(CH 2 ) p C 3-7 cycloalkyl-aryl,

(10) —(CH 2 ) p C 3-7 cycloalkyl-heteroaryl,

(11) —(CH 2 ) p C 4-l0 cycloalkenyl,

(12) —(CH 2 ) p C 4-7 cycloalkenyl-aryl,

(13) —(CH 2 ) p C 4-7 cycloalkenyl-heteroaryl,

(14) —(CH 2 ) p C 2-10 cycloheteroalkyl,

(15) —(CH 2 ) p C 2-10 cycloheteroalkenyl,

(16) —(CH 2 ) p aryl,

(17) —(CH 2 ) p aryl-C 1-8 alkyl,

(18) —(CH 2 ) p aryl-C 2-8 alkenyl,

(19) —(CH 2 ) p aryl-C 2-8 alkynyl-C 1-8 alkyl,

(20) —(CH 2 ) p aryl-C 2-8 alkynyl-C 3-7 cycloalkyl,

(21) —(CH 2 ) p aryl-C 2-8 alkynyl-C 3-7 cycloalkenyl,

(22) —(CH 2 ) p aryl-C 2-8 alkynyl-C 2-10 cycloheteroalkyl,

(23) —(CH 2 ) p aryl-C 2-8 alkynyl-C 2-10 cycloheteroalkenyl,

(24) —(CH 2 ) p aryl-C 2-8 alkynyl-aryl,

(25) —(CH 2 ) p aryl-C 2-8 alkynyl-heteroaryl,

(26) —(CH 2 ) p aryl-C 3-7 cycloalkyl,

(27) —(CH 2 ) p aryl-C 2-10 cycloheteroalkyl,

(28) —(CH 2 ) p aryl-C 2-10 cycloheteroalkenyl,

(29) —(CH 2 ) p aryl-aryl,

(30) —(CH 2 ) p aryl-heteroaryl,

(31) —(CH 2 ) p heteroaryl,

(32) —C 2-6 alkenyl-alkyl,

(33) —C 2-6 alkenyl-aryl,

(34) —C 2-6 alkenyl-heteroaryl,

(35) —C 2-6 alkenyl-C 3-7 cycloalkyl,

(36) —C 2-6 alkenyl-C 3-7 cycloalkenyl,

(37) —C 2-6 alkenyl-C 2-7 cycloheteroalkyl,

(38) —C 2-6 alkenyl-C 2-7 cycloheteroalkenyl,

(39) —C 2-6 alkynyl-(CH 2 ) 1-3 —O-aryl,

(40) —C 2-6 alkynyl-alkyl,

(41) —C 2-6 alkynyl-aryl,

(42) —C 2-6 alkynyl-heteroaryl,

(43) —C 2-6 alkynyl-C 3-7 cycloalkyl,

(44) —C 2-6 alkynyl-C 3-7 cycloalkenyl,

(45) —C 2-6 alkynyl-C 2-7 cycloheteroalkyl,

(46) —C 2-6 alkynyl-C 2-7 cycloheteroalkenyl, and

(47) —C(O)NH—(CH 2 ) 0-3 phenyl,

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 , wherein each alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloheteroalkyl, cycloheteroalkenyl, phenyl, aryl and heteroaryl is unsubstituted or substituted with 1, 2, 3 or 4 substituents independently selected from R a ,

provided that at least one of and only one of R 1 and R 2 is selected from the group consisting of:

hydrogen, halogen, —CN, —CF 3 , —C 1-6 alkyl, —C 2-6 alkenyl and —C 2-6 alkynyl;

each R 4 is independently selected from:

(1) hydrogen,

(2) halogen,

(3) —C 1-6 alkyl,

(4) —C 2-6 alkenyl,

(5) —C 2-6 alkynyl,

(6) —CN,

(7) —CF 3 ,

(8) —OH,

(9) —OC 1-6 alkyl,

(10) —NH 2 ,

(11) —NHC 1-6 alkyl,

(12) —N(C 1-6 alkyl) 2 ,

(13) —SC 1-6 alkyl,

(14) —SOC 1-6 alkyl,

(15) —SO 2 C 1-6 alkyl,

(16) —NHSO 2 C 1-6 alkyl,

(17) —NHC(O)C 1-6 alkyl,

(18) —SO 2 NHC 1-6 alkyl, and

(19) —C(O)NHC 1-6 alkyl;

R 5 is selected from:

(1) hydrogen,

(2) —C 1-6 alkyl,

(3) —CH 2 CO 2 H, and

(4) —CH 2 CO 2 C 1-6 alkyl;

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

(1) —(CH 2 ) m -halogen,

(2) oxo,

(3) —(CH 2 ) m OH,

(4) —(CH 2 ) m N(Rj) 2 ,

(5) —(CH 2 ) m NO 2 ,

(6) —(CH 2 ) m CN,

(7) —C 1-6 alkyl,

(8) —(CH 2 ) m CF 3 ,

(9) —(CH 2 ) m OCF 3 ,

(10)—O—(CH 2 ) m —OC 1-6 alkyl,

(11)—(CH 2 ) m C(O)N(Rj) 2 ,

(12)—(CH 2 ) m C(=N—OH)N(Rj) 2 ,

(13)—(CH 2 ) m OC 1-6 alkyl,

(14) —(CH 2 ) m O—(CH 2 ) m —C 3-7 cycloalkyl,

(15) —(CH 2 ) m O—(CH 2 ) m —C 2-7 cycloheteroalkyl,

(16) —(CH 2 ) m O—(CH 2 ) m -aryl,

(17) —(CH 2 ) m O—(CH 2 ) m -heterolaryl,

(18) —(CH 2 ) m SC 1-6 alkyl,

(19) —(CH 2 ) m S(O)C 1-6 alkyl,

(20) —(CH 2 ) m SO 2 C 1-6 alkyl,

(21) —(CH 2 ) m SO 2 C 3-7 cycloalkyl,

(22) —(CH 2 ) m SO 2 C 2-7 cycloheteroalkyl,

(23) —(CH 2 ) m SO 2 -aryl,

(24) —(CH 2 ) m SO 2 -heteroaryl,

(25) —(CH 2 ) m SO 2 NHC 1-6 alkyl,

(26) —(CH 2 ) m SO 2 NHC 3-7 cycloalkyl,

(27) —(CH 2 ) m SO 2 NHC 2-7 cycloheteroalkyl,

(28) —(CH 2 ) m SO 2 NH-aryl,

(29) —(CH 2 ) m SO 2 NH-heteroaryl,

(30) —(CH 2 ) m NHSO 2 —C 1-6 alkyl,

(31) —(CH 2 ) m NHSO 2 —C 3-7 cycloalkyl,

(32) —(CH 2 ) m NHSO 2 —C 2-7 cycloheteroalkyl,

(33) —(CH 2 ) m NHSO 2 -aryl,

(34) —(CH 2 ) m NHSO 2 NH-heteroaryl,

(35) —(CH 2 ) m N(R j )—C 1-6 alkyl,

(36) —(CH 2 ) m N(R j )—C 3-7 cycloalkyl,

(37) —(CH 2 ) m N(R j )—C 2-7 cycloheteroalkyl,

(38) —(CH 2 ) m N(R j )—C 2-7 cycloheteroalkenyl,

(39) —(CH 2 ) m N(R j )-aryl,

(40) —(CH 2 ) m N(R j )-heteroaryl,

(41) —(CH 2 ) m C(O)R f,

(42) —(CH 2 ) m C(O)N(R j ) 2 ,

(43) —(CH 2 ) m N(Rj)C(O)N(R j ) 2 ,

(44) —(CH 2 ) m CO 2 H,

(45) —(CH 2 ) m OCOH,

(46) —(CH 2 ) m CO 2 R f ,

(47) —(CH2) m OCOR f ,

(48) —(CH2) m C 3-7 cycloalkyl,

(49) —(CH2) m C 3-7 cycloalkenyl,

(50) —(CH2) m C 2-6 cycloheteroalkyl,

(51) —(CH2) m C 2-6 cycloheteroalkenyl,

(52) —(CH2) m aryl, and

(53) —(CH2) m heteroaryl,

wherein each CH2 is unsubstituted or substituted with 1 or 2 substituents selected from: oxo, —(CH 2 ) l-3 OH, —CN, —NH 2 , —NH(C 1-6 alkyl), —N(C 1-6 alkyl) 2 , —C 1-6 alkyl (CH 3 ) , 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, phenyl, CH 2 phenyl, heteroaryl and CH 2 heteroaryl, and wherein alkyl, cycloalkyl, cycloalkenyl, cycloheteroalkyl, cycloheteroalkenyl, aryl and heteroaryl are unsubstituted or substituted with 1, 2, 3 or 4 substituents selected from: oxo, —(CH 2 ) 0-5 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, -SO 2 C 1-6 alkyl, —C 3-7 cycloalkyl, phenyl, CH 2 phenyl, heteroaryl and CH 2 heteroaryl;

each R b is independently selected from:

(1) hydrogen,

(2) —C 1-6 alkyl,

(3) —C 3-6 cycloalkyl,

(4) —C 3-6 cycloalkenyl,

(5) —C 2-6 cycloheteroalkyl,

(6) —C 2-6 cycloheteroalkenyl,

(7) aryl,

(8) heteroaryl,

(9) —(CH 2 )t-halogen,

(10) —(CH 2 ) s —OH,

(11) —NO 2 ,

(12) —NH 2 ,

(13) —NH(C 1-6 alkyl),

(14) —N(C 1-6 alkyl) 2 ,

(15) —OC 1-6 alkyl,

(16) —(CH 2 ) q CO 2 H,

(17) —(CH 2 ) q CO 2 C 1-6 alkyl,

(18) —CF 3 ,

(19) —CN,

(20) —SO 2 C 1-6 alkyl, and

(21) —(CH 2 )sCON(Re) 2 ,

wherein each CH 2 is unsubstituted or substituted with 1 or 2 halogens, and wherein each alkyl, cycloalkyl, cycloalkenyl, cycloheteroalkyl, cycloheteroalkenyl, aryl and heteroaryl is unsubstituted or substituted with 1, 2 or 3 halogens;

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 Rf,

(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(Rh) 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, 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 R j is independently selected from:

(1) hydrogen,

(2) C 1-6 alkyl,

(3) C 3-6 cycloalkyl,

(4) —C(O)R i , and

(5) —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) C 4-7 cycloalkyl,

(3) C 4-7 cycloalkenyl,

(4) C 3-7 cycloheteroalkyl,

(5) C 3-7 cycloheteroalkenyl,

(6) aryl, and

(7) 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 , —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; and

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

2. The compound according to claim 1 wherein:

T is N;

U is CR 1 ;

V is CR 2 ;

W is CR 4 ;

X is selected from:

(1) —O—, and

(2) —O—CH 2 —;

Y is selected from:

(1) C 3-l0 cycloalkyl,

(2) C 3-l0 cycloalkenyl,

(3) C 2-10 cycloheteroalkyl,

(4) C 2-10 cycloheteroalkenyl,

(5) aryl, and

(6) heteroaryl,

wherein cycloalkyl, cycloalkenyl, cycloheteroalkyl, cycloheteroalkenyl, aryl and heteroaryl are unsubstituted or substituted with 1, 2, 3 or 4 substituents selected from R b ;

Z is selected from:

(1) oxo,

(2) —CF 3 ,

(3) —C 1-6 alkyl,

(4) —(CH 2 ) t -halogen,

(5) —(CH 2 ) n CO 2 H,

(6) —(CH 2 ) n OH, and

(7) —(CH 2 )SO 2 C 1-6 alkyl,

wherein each CH 2 is unsubstituted or substituted with 1 or 2 substituents selected from C 1-6 alkyl, —OH and —NH 2 , and wherein each alkyl is unsubstituted or substituted with 1, 2, 3 or 4 substituents selected from R c ;

each R 1 and R 2 is independently selected from:

(1) hydrogen,

(2) halogen,

(3) CN,

(4) CF 3 ,

(5) —C l-6 alkyl,

(6) —C 2-6 alkenyl,

(7) —C 2-6 alkynyl,

(8) —(CH 2 ) p C 3-10 cycloalkyl,

(9) —(CH 2 ) p C 3-7 cycloalkyl-aryl,

(10) —(CH 2 ) p C 3-7 cycloalkyl-heteroaryl,

(11) —(CH 2 ) p C 4-10 cycloalkenyl,

(12) —(CH 2 ) p C 4-7 cycloalkenyl-aryl,

(13) —(CH 2 ) p C 4-7 cycloalkenyl-heteroaryl,

(14) —(CH 2 ) p C 2-10 cycloheteroalkyl,

(15) —(CH 2 ) p C 2-10 cycloheteroalkenyl,

(16) —(CH 2 ) p aryl,

(17) —(CH 2 ) p aryl—C 3-7 cycloalkyl,

(18) —(CH 2 ) p aryl—C 2-7 cycloheteroalkyl,

(19) —(CH 2 ) p aryl-aryl,

(20) —(CH 2 ) p aryl-heteroaryl,

(21) —(CH 2 ) p heteroaryl,

(22) —C 2-6 alkenyl-alkyl,

(23) —C 2-6 alkenyl-aryl,

(24) —C 2-6 alkenyl-heteroaryl,

(25) —C 2-6 alkenyl—C 3-7 cycloalkyl,

(26) —C 2-6 alkenyl—C 3-7 cycloalkenyl,

(27) —C 2-6 alkenyl—C 2-7 cycloheteroalkyl,

(28) —C 2-6 alkenyl—C 2-7 cycloheteroalkenyl,

(29) —C 2-6 alkynyl—(CH 2 ) 1-3 —O—aryl,

(30) —C 2-6 alkynyl-alkyl,

(31) —C 2-6 alkynyl-aryl,

(32) —C 2-6 alkynyl-heteroaryl,

(33) —C 2-6 alkynyl—C 3-7 cycloalkyl,

(34) —C 2-6 alkynyl—C 3-7 cycloalkenyl,

(35) —C 2-6 alkynyl—C 2-7 cycloheteroalkyl,

(36) —C 2-6 alkynyl—C 2-7 cycloheteroalkenyl, and

(37) —C(O)NH—(CH 2 ) 0-3 phenyl,

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 , wherein each alkyl, alkenyl and alkynyl is unsubstituted or substituted with 1, 2 or 3 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 cycloalkyl, cycloalkenyl, cycloheteroalkyl, cycloheteroalkenyl, phenyl, aryl and heteroaryl is unsubstituted or substituted with 1, 2, 3 or 4 substituents independently selected from R a , provided that at least one of and only one of R 1 and R 2 is selected from the group consisting of: hydrogen, halogen, —CN, —CF 3 , —C 1-6 alkyl, —C 2-6 alkenyl and—C 2-6 alkynyl;

each R 4 is independently selected from:

(1) hydrogen,

(2) halogen,

(3) —C 1-6 alkyl,

(4) —C 2-6 alkenyl,

(5) —C 2-6 alkenyl,

(6) —CN,

(7) —CF 3 ,

(8) —OH,

(9) —OC 1-6 alkyl,

(10) —NH 2 ,

(11) —NHC 1-6 alkyl,

(12) —N(C 1-6 alkyl) 2 ,

(13) —SC 1-6 alkyl,

(14) —SOC 1-6 alkyl,

(15) —SO 2 C 1-6 alkyl,

(16) —NHSO 2 C 1-6 alkyl,

(17) —NHC(O)C 1-6 alkyl,

(18) —SO 2 NHC 1-6 alkyl, and

(19) —C(O)NHC 1-6 alkyl;

R 5 is selected from:

(1) hydrogen,

(2) —C 1-6 alkyl,

(3) —CH 2 CO 2 H, and

(4) —CH 2 CO 2 C 1-6 alkyl;

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

(1) halogen,

(2) oxo,

(3) —(CH 2 ) m OH,

(4) —(CH 2 ) m N(Rj) 2 ,

(5) —(CH 2 ) m NO 2 ,

(6) —(CH 2 ) m CN,

(7) —C 1-6 alkyl,

(8) —(CH 2 ) m CF 3 ,

(9) —(CH 2 ) m OCF 3 ,

(10) —OCH 2 OC 1-6 alkyl,

(11) —(CH 2 ) m C(O)N(Rj) 2 ,

(12) —(CH 2 ) m C(=N—OH)N(Rj) 2 ,

(13) —(CH 2 ) m OC 1-6 alkyl,

(14) —(CH 2 ) m O—(CH 2 ) m —C 3-7 cycloalkyl,

(15) —(CH 2 ) m O—(CH 2 ) m —C 2-7 cycloheteroalkyl,

(16) —(CH 2 ) m O—(CH 2 ) m -aryl,

(17) —(CH 2 ) m O—(CH 2 ) m -heteroaryl,

(18) —(CH 2 ) m SC 1-6 alkyl,

(19) —(CH 2 ) m S(O)C 1-6 alkyl,

(20) —(CH 2 ) m SO 2 C 1-6 alkyl,

(21) —(CH 2 ) m SO 2 C 3-7 cycloalkyl,

(22) —(CH 2 ) m SO 2 C 2-7 cycloheteroalkyl,

(23) —(CH 2 ) m SO 2 -aryl,

(24) —(CH 2 ) m SO 2 -heteroaryl,

(25) —(CH 2 ) m SO 2 NHC 1-6 alkyl,

(26) —(CH 2 ) m SO 2 NHC 3-7 cycloalkyl,

(27) —(CH 2 ) m SO 2 NHC 2-7 cycloheteroalkyl,

(28) —(CH 2 ) m SO 2 NH-aryl,

(29) —(CH 2 ) m SO 2 NH-heteroaryl,

(30) —(CH 2 ) m NHSO 2 —C 1-6 a1kyl,

(31) —(CH 2 ) m NHSO 2 —C 3-7 cycloalkyl,

(32) —(CH 2 ) m NHSO 2 —C 2-7 cycloheteroalkyl,

(33) —(CH 2 ) m NHSO 2 -aryl,

(34) —(CH 2 ) m NHSO 2 NH-heteroaryl,

(35) —(CH 2 ) m C(O)R f ,

(36) —(CH 2 ) m C(O)N(Rj) 2 ,

(37) —(CH 2 ) m N(Rj)C(O)N(Rj) 2 ,

(38) —(CH 2 ) m CO 2 H,

(39) —(CH 2 ) m OCOH,

(40) —(CH 2 ) m CO 2 Rf,

(41) —(CH 2 ) m OCOR f ,

(42) —(CH 2 ) m C 3-7 cycloalkyl,

(43) —(CH 2 ) m C 3-7 cycloalkenyl,

(44) —(CH 2 ) m C 2-6 cycloheteroalkyl,

(45) —(CH 2 ) m C 2-6 cycloheteroalkenyl,

(46) —(CH 2 ) m aryl, and

(47) —(CH 2 ) m heteroaryl,

wherein each CH 2 is unsubstituted or substituted with 1 or 2 substituents selected from: oxo, —(CH 2 ) 0-3 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, phenyl, CH 2 phenyl, heteroaryl and CH 2 heteroaryl, and wherein alkyl, cycloalkyl, cycloalkenyl, cycloheteroalkyl, cycloheteroalkenyl, aryl and heteroaryl are unsubstituted or substituted with 1, 2, 3 or 4 substituents selected from: oxo, —(CH 2 ) 0-3 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, -SO 2 C 1-6 alkyl, —C 3-7 cycloalkyl, phenyl, CH2phenyl, heteroaryl and CH 2 heteroaryl;

each R b is independently selected from:

(1) hydrogen,

(2) —C 1-6 alkyl,

(3) —C 3-6 cycloalkyl,

(4) —C 3-6 cycloalkenyl,

(5) —C 2-6 cycloheteroalkyl,

(6) —C 2-6 cycloheteroalkenyl,

(7) aryl,

(8) heteroaryl,

(9) —(CH 2 )t-halogen,

(10) —(CH 2 )s-OH,

(11) —NO 2 ,

(12) —NH 2 ,

(13) —NH(C 1-6 ablkyl),

(14) —N(C 1-6 alkyl) 2 ,

(15) —OC 1-6 alkyl,

(16) —(CH 2 ) q CO 2 H,

(17) —(CH 2 ) q CO 2 C 1-6 alkyl,

(18) —CF 3 ,

(19) —CN,

(20) —SO 2 C 1-6 alkyl, and

(21) —(CH 2 ) s CON(R e ) 2 ,

wherein each CH 2 is unsubstituted or substituted with 1 or 2 halogens, and wherein each alkyl, cycloalkyl, cycloalkenyl, cycloheteroalkyl, cycloheteroalkenyl, aryl and heteroaryl is unsubstituted or substituted with 1, 2 or 3 halogens;

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 Rf,

(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 , —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, —C3 — 7cycloalkyl 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 l-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 , and

(5) —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) C4 — 7cycloalkyl,

(3) C4 — 7cycloalkenyl,

(4) C3 — 7cycloheteroalkyl,

(5) C3 — 7cycloheteroalkenyl,

(6) aryl, and

(7) 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 , —C 1-6 alkyl, —OC 1-6 alkyl, halogen, —CH 2 F, —CHF2, —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; and

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

or a pharmaceutically acceptable salt thereof.

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

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

(1) C 3-10 cycloalkyl,

(2) C 2-10 cycloheteroalkyl, and

(3) aryl,

wherein cycloalkyl, cycloheteroalkyl and aryl are unsubstituted or substituted with 1, 2, 3 or 4 substituents selected from Rb; or a pharmaceutically acceptable salt thereof.

5. The compound according to claim 4 , wherein Y is selected from:

(1) C 3-7 cycloalkyl,

(2) C 2-l0 cycloheteroalkyl, and

(3) phenyl,

wherein each cycloalkyl, cycloheteroalkyl and phenyl is unsubstituted or substituted with 1, 2, 3 or 4 substituents selected from R b ; or a pharmaceutically acceptable salt thereof.

6. The compound according to claim 2 , wherein Z is selected from:

(1) —(CH 2 ) n CO 2 H, and

(2) —(CH 2 ) n OH,

wherein each CH 2 is unsubstituted or substituted with 1 or 2 substituents selected from C 1-6 alkyl, —OH and —NH 2 ; or a pharmaceutically acceptable salt thereof.

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

(1) halogen,

(2) —C 4-10 cycloalkenyl,

(3) -phenyl,

(4) -phenyl—C 2-8 alkynyl—C 1-8 alkyl,

(5) -phenyl—C 2-3 alkynyl—C 3-7 cycloalkyl,

(6) -phenyl—C 2-3 alkynyl—C 2-10 cycloheteroalkyl,

(7) -phenyl—C 3-7 cycloalkyl,

(8) -phenyl—C 2-7 cycloheteroalkyl,

(9) -phenyl—C 2-10 cycloheteroalkenyl,

(10) -phenyl-aryl,

(11) -phenyl-heteroaryl,

(12) -heteroaryl, and

(13) —C 2-6 alkynyl-phenyl,

and wherein each alkyl, alkynyl, cycloalkyl, cycloalkenyl, cycloheteroalkyl, cycloheteroalkenyl, phenyl, aryl and heteroaryl is unsubstituted or substituted with 1, 2, 3 or 4 substituents independently selected from R a , provided that at least one of and only one of R 1 and R 2 is selected from halogen; or a pharmaceutically acceptable salt thereof.

8. The compound according to claim 7 , wherein R 1 is independently selected from:

(1) —C 4-10 ocycloalkenyl,

(2) -phenyl,

(3) -phenyl—C 2 alkynylC 1-5 alkyl,

(4) -phenyl—C 2-3 alkynyl- C 3-7 cycloalkyl,

(5) -phenyl—C 2-3 alkynyl—C 2-10 cycloheteroalkyl,

(6) -phenyl—C 3-7 cycloalkyl,

(7) -phenyl—C 2-7 cycloheteroalkyl,

(8) -phenyl—C 2-10 cycloheteroalkenyl,

(9) -phenyl-phenyl,

(10) -phenyl-heteroaryl,

(11) -heteroaryl, and

(12) —C 2-6 alkynyl-phenyl,

wherein each alkyl, alkynyl, cycloalkyl, cycloalkenyl, cycloheteroalkyl, cycloheteroalkenyl, phenyl and heteroaryl is unsubstituted or 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.

9. The compound according to claim 8 , wherein each R 1 is independently selected from:

(1) -phenyl—C 2-7 cycloheteroalkyl,

(2) -phenyl—C 2-10 cycloheteroalkenyl,

(3) -phenyl-phenyl, and

(4) -phenyl-heteroaryl,

wherein each cycloheteroalkyl, cycloheteroalkenyl, heteroaryl and phenyl is unsubstituted or substituted with 1, 2, 3 or 4 substituents independently selected from Ra; and R2 is halogen;

or a pharmaceutically acceptable salt thereof.

10. The compound according to claim 2 , wherein each R 1 and R 2 is independently selected from:

(1) halogen,

(2) —C 4-10 cycloalkenyl,

(3) -phenyl,

(4) -phenyl—C 3-7 cycloalkyl,

(5) -phenyl—C 2-7 cycloheteroalkyl,

(6) -phenyl-aryl,

(7) -phenyl-heteroaryl,

(8) -heteroaryl, and

(9) —C 2-6 alkynyl-phenyl,

wherein each alkynyl is unsubstituted or substituted with 1, 2 or 3 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 cycloalkyl, cycloalkenyl, cycloheteroalkyl, phenyl, aryl and heteroaryl is unsubstituted or substituted with 1, 2, 3 or 4 substituents independently selected from R a , provided that at least one of and only one of R 1 and R 2 is selected from halogen; or a pharmaceutically acceptable salt thereof.

11. The compound according to claim 10 , wherein R 1 is independently selected from:

(1) —C 4-10 ocycloalkenyl,

(2) -phenyl,

(3) -phenyl—C 3-7 cycloalkyl,

(4) -phenyl—C 2-7 cycloheteroalkyl,

(5) -phenyl-phenyl,

(6) -phenyl-heteroaryl,

(7) -heteroaryl, and

(8) —C2 — 6alkynyl-phenyl,

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

R2 is selected from: halogen;

or a pharmaceutically acceptable salt thereof.

12. The compound according to claim 11 , wherein each R1 is independently selected from:

(1) -phenyl—C 2-7 cycloheteroalkyl, and

(2) -phenyl-phenyl,

wherein each cycloheteroalkyl and phenyl is unsubstituted or 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.

13. The compound according to claim 2 , wherein R4 is hydrogen or absent; and R 5 is hydrogen; or a pharmaceutically acceptable salt thereof.

14. The compound according to claim 1 wherein:

T is N;

U is —CR 1 —;

V is —CR 2 —;

W is —CR4—;

X is selected from:

(1) —O—, and

(2) —O—CH 2 —;

Y is selected from:

(1) —C 3-10 ycloalkyl,

(2) —C 2-10 cycloheteroalkyl, and

(3) -phenyl,

wherein cycloalkyl, cycloheteroalkyl and phenyl are unsubstituted or substituted with 1, 2, 3 or 4 substituents selected from R b ;

Z is selected from:

(1) oxo,

(2) —CF 3 ,

(3) —C 1-6 alkyl,

(4) —(CH 2 ) t -halogen,

(5) —(CH 2 ) n CO 2 H,

(6) —(CH 2 ) n OH, and

(7) —(CH 2 ) n SO 2 C 1-6 alkyl,

wherein each CH 2 is unsubstituted or substituted with 1 or 2 substituents selected from C 1-6 alkyl, —OH and —NH 2 , and wherein each alkyl is unsubstituted or substituted with 1, 2, 3 or 4 substituents selected from R c ;

R 1 is independently selected from:

(1) —C 4-10 cycloalkenyl,

(2) -phenyl,

(3) -phenyl—C 2 alkynylC 1-5 alkyl,

(4) -phenyl—C 2-3 alkynyl- C 3-7 cycloalkyl,

(5) -phenyl—C 2-3 alkynyl—C 2-10 cycloheteroalkyl,

(6) -phenyl—C 3-7 cycloalkyl,

(7) -phenyl—C 2-7 cycloheteroalkyl,

(8) -phenyl—C 2-10 cycloheteroalkenyl,

(9) -phenyl-phenyl,

(10) -phenyl-heteroaryl,

(11) -heteroaryl, and

(12) —C 2-6 alkynyl-phenyl,

wherein each alkyl, alkynyl, cycloalkyl, cycloalkenyl, cycloheteroalkyl, cycloheteroalkenyl, 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 hydrogen; and

R 5 is hydrogen;

or a pharmaceutically acceptable salt thereof.

15. The compound according to claim 2 wherein:

T is N;

U is —CR 1 —;

V is —CR 2 —;

W is —CR 4 —;

X is selected from:

(1) —O—, and

(2) —O—CH 2 —;

Y is selected from:

(1) C 3-10 cycloalkyl,

(2) C 2-10 cycloheteroalkyl, and

(3) phenyl,

wherein cycloalkyl, cycloheteroalkyl and phenyl are unsubstituted or substituted with 1, 2, 3 or 4 substituents selected from R b ;

Z is selected from:

(1) oxo,

(2) CF 3 ,

(3) —C 1-6 alkyl,

(4) —(CH 2 ) t -halogen,

(5) —(CH2) n CO 2 H,

(6) —(CH2) n OH, and

(7) —(CH2) n SO 2 C 1-6 alkyl,

wherein each CH 2 is unsubstituted or substituted with 1 or 2 substituents selected from C 1-6 alkyl, —OH and —NH 2 , and wherein each alkyl is unsubstituted or substituted with 1, 2, 3 or 4 substituents selected from R c ;

R 1 is independently selected from:

(1) —C 4-10 cycloalkenyl,

(2) -phenyl,

(3) -phenyl—C 3-7 cycloalkyl,

(4) -phenyl—C 2-7 cycloheteroalkyl,

(5) -phenyl-heteroaryl,

(6) -phenyl-phenyl,

(7) -heteroaryl, and

(8) —C 2-6 alkynyl-phenyl,

wherein each alkynyl is unsubstituted or substituted with 1, 2 or 3 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 cycloalkyl, cycloalkenyl, 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 hydrogen; and

R 5 is hydrogen;

or a pharmaceutically acceptable salt thereof.

16. The compound according to claim 2 wherein:

T is N;

U is —CR 1 —;

V is —CR 2 —;

W is —CR 4 —;

X is —O—;

Y is selected from:

(1) C 3-7 cycloalkyl,

(2) C 2-10 cycloheteroalkyl, and

(3) phenyl,

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

Z is selected from:

(1) —(CH 2 ) n CO 2 H, and

(2) —(CH 2 ) n OH,

wherein each CH2 is unsubstituted or substituted with 1 or 2 substituents selected from C 1-6 alkyl and —OH;

R 1 is selected from:

(1) -phenyl—C 2-7 cycloheteroalkyl, and

(2) -phenyl-phenyl,

wherein each cycloheteroalkyl and phenyl 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 hydrogen; and

R 5 is hydrogen;

or a pharmaceutically acceptable salt thereof.

17. The compound according to claim 16 , selected from:

or a pharmaceutically acceptable salt thereof.

18. 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 C 2-10 cycloheteroalkyl, wherein each cycloheteroalkyl is unsubstituted or substituted with 1, 2, 3 or 4 substituents selected from R b ;

Z is selected from: —(CH 2 ) n OH;

R 1 is independently selected from:

(1) -phenyl—C 2-10 cycloheteroalkenyl,

(2) -biphenyl, and

(3) -phenyl-heteroaryl,

wherein each cycloheteroalkenyl, phenyl, biphenyl 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 hydrogen; and

R 5 is hydrogen;

or a pharmaceutically acceptable salt thereof.

19. The compound according to claim 18 , selected from:

or a pharmaceutically acceptable salt thereof.

20. A composition comprising a compound according to claim 1 and a pharmaceutically acceptable carrier.

21. A composition comprising a compound according to claim 1 and a compound selected from simvastatin, ezetimibe, taranabant and sitagliptin; and a pharmaceutically acceptable carrier.

22. A method of treating a disorder, condition or disease responsive to the activation of AMP-activated protein kinase in a patient in need thereof comprising administration of a therapeutically effective amount of a compound according to claim 1 , wherein the disorder, condition, or disease is selected from the group consisting of:

Type 2 diabetes, hyperglycemia, Metabolic Syndrome, obesity, hypercholesterolemia, hypertension, and cancer.