This invention relates to certain novel imidazoline compounds and analogues thereof, to their use for the treatment of diabetes, diabetic complications, metabolic disorders, or related diseases where impaired glucose disposal is present, to pharmaceutical compositions comprising them, and to processes for their preparation.
The compounds have the following formula:
wherein

X is -O-, -S-, or -NR 5 -;
R 5 is hydrogen, C 1-8 alkyl, or an amino protecting group;
R 1 , R 1' , R 2 , and R 3 are independently hydrogen or C 1-8 alkyl;
R 1 and R 2 optionally together form a bond and R 1' and R 3 are independently hydrogen or C 1-8 alkyl;
R 1 and R 2 optionally combine together with the carbon atoms to which they are attached form a C 3-7 carbocyclic ring and R 1' and R 3 are independently hydrogen or C 1-8 alkyl;
R 1 and R 1' together with the carbon atom to which they are attached optionally combine to form a C 3-7 spirocarbocyclic ring and R 2 and R 3 are independently hydrogen or C 1-8 alkyl;
R 2 and R 3 together with the carbon atom to which they are attached optionally combine to form a C 3 . 7 spirocarbocyclic and R 1 and R 1' are independently hydrogen or C 1-8 alkyl;
n is 0, 1, or 2;
m is 1 or2; 2;
m' is 0, 1, or 2;
q' is 0,1,2,3,4, or 5;
R 4 is


Y is -O-, -S-, or -NR 8 -;
Y' is -O- or -S-;
R 6 and R 7 are independently hydrogen, C 1-8 alkyl, C 3-7 cycloalkyl, C 1-8 alkoxy, C 1-8 alkylthio, halo C 1-8 alkylthio, C 1-8 alkylsulfinyl, C 1-8 alkylsulfonyl. C 3-7 cycloalkoxy, aryl-C 1-8 alkoxy, halo, halo-C 1-8 alkyl, halo-C 1-8 alkoxy, nitro, -NR 10 R 11 , -CONR 10 R 11 , aryl C 1-8 alkyl, optionally substituted heterocyclyl, optionally substituted phenyl, optionally substituted naphthyl, optionally halo substituted acylamino, cyano, hydroxy, COR 12 , halo C 1-8 alkylsulfinyl, or halo C 1-8 alkylsulfonyl, or alkoxyalkyl of the formula

        CH 3 (CH 2 ) p -O-(CH 2 ) q -O-;


where

p is 0, 1, 2, 3, or 4; and
q is 1, 2, 3, 4, or 5;
R 12 is C 1-8 alkyl or optionally substituted phenyl;
R 8 is hydrogen, C 1-8 alkyl, halo-C 1-8 alkyl, optionally substituted phenyl, optionally substituted heterocyclyl, COO C 1-8 alkyl, optionally substituted COaryl, COC 1-8 alkyl, SO 2 C 1-8 alkyl, optionally substituted SO 2 aryl, optionally substituted phenyl-C 1-8 alkyl, CH 3 (CH 2 ) p -O-(CH 2 ) q -O-;
R 9 is hydrogen, halo, C 1-8 alkyl, halo C 1-8 alkyl, C 1-8 alkylthio, halo C 1-8 alkylthio, C 3-7 cycloalkylthio, optionally substituted arylthio or heteroarylthio, C 1-8 alkoxy, C 3-8 cycloalkoxy, optionally substituted aryloxy, optionally substituted heteroaryloxy, or optionally substituted aryl or heteroaryl, C 3-7 cycloalkyl, halo C 3-7 cycloalkyl, C 3-7 cycloalkenyl, cyano, COOR 10 ,CONR 10 R 11 or NR 10 R 11 ,C 2-6 alkenyl, optionally substituted heterocyclyl, optionally substituted aryl C 1-8 alkyl, optionally substituted heteroaryl C 1-8 alkyl in which the alkyl group can be substituted by hydroxy, or C 1-8 alkyl substituted by hydroxy,
R 10 and R 11 are independently hydrogen, C 1-8 alkyl, optionally substituted aryl C 1-8 alkyl, optionally substituted phenyl, or R 10 and R 11 together with the nitrogen atom to which they are attached may combine to form a ring with up to six carbon atoms which optionally may be substituted with up to two C 1-8 alkyl groups or one carbon atom may be replaced by oxygen or sulfur;
R 14 and R 16 are independently hydrogen, halo, C 1-8 alkyl, C 3-7 cycloalkyl, C 3-7 cycloalkoxy, C 3-7 cycloalkylC 1-8 alkoxy, halo-C 1-8 alkyl, halo-C 1-8 alkoxy, C 1-8 alkoxy, carbo(C 1-8 )alkoxy, optionally substituted aryl, or optionally substituted heteroaryl;
R 15 and R 17 are independently hydrogen, halo, C 1-8 alkoxy, C 3-7 -cycloalkyl, C 3-7 cycloalkylC 1-8 alkoxy, C 1-8 alkyl, C 3-7 cycloalkoxy, hydroxy, halo C 1-8 alkoxy, carbo(C 1-8 )alkoxy, optionally substituted phenyl, optionally substituted phenyl-C 1-8 alkyl, optionally substituted phenyloxy, optionally substituted phenyl-C 1-8 alkoxy, (tetrahydropyran-2-yl)methoxy, C 1-8 alkyl-S(O) m -, optionally substituted aryl-C 1-8 alkyl-S(O) m ·-, CH 3 (CH 2 ) p -Z 1 -(CH 2 ) q -Z 2 -, or Z 3 -(CH 2 ) q' -Z 2 -;
Z 1 and Z 2 are independently abond, O, S, SO, SO 2 , sulphoximino, or NR 10 ; and
Z 3 is hydroxy, protected hydroxy, NR 10 R 11 , protected amino, SH or protected SH;
   provided that when R 1 , R 1 ', R 2 and R 3 are all hydrogen; n is 0; R 4 is naphthyl; and R 14 R 15 and R 16 , or R 15 , R 16 and R 17 are all hydrogen, then R 17 or R 14 , respectively, is other than halo, methoxy, or C 1-6 alkyl.
   or a pharmaceutically acceptable salt or ester thereof.