Phenoxyether derivatives as PPAR modulators

The compound having the structural formula X,

• or a pharmaceutically acceptable salt or stereoisomer thereof, wherein:
• is a 5- or 6-membered heteroaryl or heterocyclyl, wherein heteroaryl and heterocyclyl being optionally substituted with one or more substituents independently selected from R8;
• A is:
• a bond, CH2, (CH2)2, O, S;
• or A and R1 or A and R2 together being a 3- to 6-membered carbocyclyl when A is a carbon;
• n is:
• 1,2,3,4,5 or 6;
• p is:
• 1 or 2;
• r is:
• 1,2,3, or 4;
• R1 and R2 are each independently:
• hydrogen, C1-C6 alkyl, or R1 and R2 together being a 3- to 8-membered carbocyclic ring;
• R3 and R4 are each independently:
• hydrogen,
• nitro,
• cyano,
• hydroxyl,
• halo,
• haloalkyl,
• haloalkyloxy,
• C1-C6 alkyl,
• C1-C6 alkoxy, or
• C3-C8 cycloalkyl
• R5 is:
• hydrogen,
• nitro,
• cyano,
• hydroxyl,
• halo,
• haloalkyl,
• haloalkyloxy,
• aryloxy,
• C1-C6 alkyl,
• C1-C6 alkoxy,
• [T]-aryl,
• [T]-heteroaryl,
• [T]-heterocyclyl,
• [T]-(CH2)nC3-C8 cycloalkyl,
• C(O)pR7,
• O(CH2)nR7,
• SR7,
• S(O)pR7 or
• OS(O)pR7,
• wherein aryl, aryloxy, alkyl, heteroaryl, heterocyclyl and cycloalkyl are being optionally substituted with one or more substituents independently selected from R8;
• [T] is:
• a bond, O, C(O), S, NR7, or C1-C6 alkyl;
• R6 is:
• hydrogen, C1-C6 alkyl or aminoalkyl;
• R7 is:
• hydrogen,
• C1-C6 alkyl,
• C3-8 cycloalkyl,
• aryl,
• heteroaryl or
• heterocyclyl,
• wherein alkyl, cycloalkyl, aryl, heteroaryl or heterocyclyl being optionally substituted with one or more substituents independently selected from R8, and
• R8 is:
• hydrogen, nitro, cyano, hydroxyl, halo, haloalkyl, haloalkyloxy, aryloxy, oxo, acyl, C1-C6 alkyl, C1-C6 alkoxy or C3-C8 cycloalkyl.

The compound having the structural formula XII,

• or a pharmaceutically acceptable salt or stereoisomer thereof;
• A is:
• a bond, CH2, (CH2)2, O, S;
• or A and R1 or A and R2 together being a 3- to 6-membered carbocyclyl when A is a carbon;
• Q is COOR6;
• n is:
• 1,2,3,4,5 or 6;
• p is:
• 1 or 2;
• r is:
• 1,2,3, or 4;
• R1 and R2 are each independently:
• hydrogen, C1-C6 alkyl, or R1 and R2 together being a 3- to 8-membered carbocyclic ring;
• R3 and R4 are each independently:
• hydrogen,
• nitro,
• cyano,
• hydroxyl,
• halo,
• haloalkyl,
• haloalkyloxy,
• C1-C6 alkyl,
• C1-C6 alkoxy, or
• C3-C8 cycloalkyl
• R5 is:
• hydrogen,
• nitro,
• cyano,
• hydroxyl,
• halo,
• haloalkyl, haloalkyloxy,
• aryloxy,
• C1-C6 alkyl,
• C1-C6 alkoxy,
• [T]-aryl,
• [T]-heteroaryl,
• [T]-heterocyclyl,
• [T]-(CH2)nC3-C8 cycloalkyl,
• C(O)pR7,
• O(CH2)nR7,
• SR7,
• S(O)pR7, or
• OS(O)pR7,
• wherein aryl, aryloxy, alkyl, heteroaryl, heterocyclyl and cycloalkyl are being optionally substituted with one or more substituents independently selected from R8;
• [T] is:
• a bond, O, C(O), S, NR7, or C1-C6 alkyl;
• R6 is:
• hydrogen, C1-C6 alkyl or aminoalkyl;
• R7 is:
• hydrogen,
• C1-C6 alkyl,
• C3-C8 cycloalkyl,
• aryl,
• heteroaryl or
• heterocyclyl,
• wherein alkyl, cycloalkyl, aryl, heteroaryl or heterocyclyl being optionally substituted with one or more substituents independently selected from R8;
• and
• R8 is:
• hydrogen, nitro, cyano, hydroxyl, halo, haloalkyl, haloalkyloxy, aryloxy, oxo, acyl, C1-C6 alkyl, C1-C6 alkoxy or C3-C8 cycloalkyl.

A compound selected from the group consisting of the following compounds:

• No.
• Structure
• Name
• 1
• 3-{4-[3-(4-Chloro-2- phenoxy-phenoxy)- phenoxy]-2-methyl- phenyl}-propionic acid
• 2
• 3-{4-[3-(2-Benzoyl-4- ethyl-phenoxy)-phenoxy]- 2-methyl-phenyl}- propionic acid
• 3
• 3-{4-[3-(4-Ethyl-2- phenoxy-phenoxy)- phenoxy]-2-methyl- phenyl}-propionic acid
• 4
• 3-{4-[3-(2-Benzoyl-4- chloro-phenoxy)- phenoxy]-2-methyl- phenyl}-propionic acid
• 5
• 3-{4-[3-(2-Benzoyl- phenoxy)-phenoxy]-2- methyl-phenyl}-propionic acid
• 6
• 3-{2-Methyl-4-[3-(2- phenoxy-phenoxy)- phenoxy]-phenyl}- propionic acid
• 7
• 3-{2-Methyl-4-[3-(2- phenoxy-4- trifluoromethyl-phenoxy)- phenoxy]-phenyl}- propionic acid
• 8
• 3-{4-[3-(4-Chloro-2- phenoxy-phenoxy)-5- fluoro-phenoxy]-2-methyl- phenyl}-propionic acid
• 9
• 3-{4-[3-(4-Ethyl-2- phenoxy-phenoxy)-5- fluoro-phenoxy]-2-methyl- phenyl}-propionic acid
• 10
• 3-(4-{3-[4-Ethyl-2-(1- methyl-1-phenyl-ethyl)- phenoxy]-5-fluoro- phenoxy}-2-methyl- phenyl)-propionic acid
• 11
• 3-{4-[3-(4-Ethyl-2- phenoxy-phenoxy)-5- fluoro-phenoxy]-2-methyl- phenyl}-propionic acid
• 12
• 3-{4-[3-(4-Chloro-2- phenoxy-phenoxy)-5- methyl-phenoxy]-2- methyl-phenyl}-propionic acid
• 13
• 3-{4-[3-(2-Benzoyl-4- chloro-phenoxy)-5- methyl-phenoxy]-2- methyl-phenyl}-propionic acid
• 14
• 3-{2-Methyl-4-[3-methyl- 5-(2-pyridin-3-yl-4- trifluoromethyl-phenoxy)- phenoxy]-phenyl}- propionic acid
• 15
• 3-{2-Methyl-4-[3-methyl- 5-(2-pyridin-2-yl-4- trifluoromethyl-phenoxy)- phenoxy]-phenyl}- propionic acid
• 16
• 3-{4-[3-(2′-Acetyl-5- trifluoromethyl-biphenyl- 2-yloxy)-5-methyl- phenoxy]-2-methyl- phenyl}-propionic acid
• 17
• 3-{4-[3-(4′- Methanesulfonyl-5- trifluoromethyl-biphenyl- 2-yloxy)-5-methyl- phenoxy]-2-methyl- phenyl}-propionic acid
• 18
• 3-{2-Methyl-4-[3-methyl- 5-(2′-trifluoromethoxy-5- trifluoromethyl-biphenyl- 2-yloxy)-phenoxy]- phenyl}-propionic acid
• 19
• 3-{2-Methyl-4-[3-methyl- 5-(2-phenoxy-4- trifluoromethyl-phenoxy)- phenoxy]-phenyl}- propionic acid
• 20
• 3-(2-Methyl-4-{3-methyl- 5-[2-(pyridin-2-yloxy)-4- trifluoromethyl-phenoxy]- phenoxy}-phenyl)- propionic acid
• 21
• 3-(2-Methyl-4-{3-methyl- 5-[2-(2-oxo-2H-pyridin-1- yl)-4-trifluoromethyl- phenoxy]-phenoxy}- phenyl)-propionic acid
• 22
• 3-(2-Methyl-4-{3-methyl- 5-[2-(pyridin-3-yloxy)-4- trifluoromethyl-phenoxy]- phenoxy}-phenyl)- propionic acid
• 23
• 3-{2-Methyl-4-[3-methyl- 5-(2-o-tolyloxy-4- trifluoromethyl-phenoxy)- phenoxy]-phenyl}- propionic acid
• 24
• 3-{2-Methyl-4-[3-methyl- 5-(2-m-tolyloxy-4- trifluoromethyl-phenoxy)- phenoxy]-phenyl}- propionic acid
• 25
• 3-{2-Methyl-4-[3-methyl- 5-(2-p-tolyloxy-4- trifluoromethyl-phenoxy)- phenoxy]-phenyl}- propionic acid
• 26
• 3-(4-{3-[2-(3,5-Difluoro- phenoxy)-4- trifluoromethyl-phenoxy]- 5-methyl-phenoxy}-2- methyl-phenyl)-propionic acid
• 27
• 3-{4-[3-Fluoro-5-(2- phenoxy-4- trifluoromethyl-phenoxy)- phenoxy]-2-methyl- phenyl}-propionic acid
• 28
• 3-{4-[3-Fluoro-5-(2- pyridin-2-yl-4- trifluoromethyl-phenoxy)- phenoxy]-2-methyl- phenyl}-propionic acid
• 29
• 3-{4-[3-Fluoro-5-(2- pyridin-3-yl-4- trifluoromethyl-phenoxy)- phenoxy]-2-methyl- phenyl}-propionic acid
• 30
• 3-{4-[3-Chloro-5-(2- phenoxy-4- trifluoromethyl-phenoxy)- phenoxy]-2-methyl- phenyl}-propionic acid
• 31
• 3-(4-{3-Chloro-5-[2-(3- fluoro-phenoxy)-4- trifluoromethyl-phenoxy]- phenoxy}-2-methyl- phenyl)-propionic acid
• 32
• 3-{4-[3-Chloro-5-(2- pyridin-2-yl-4- trifluoromethyl-phenoxy)- phenoxy]-2-methyl- phenyl}-propionic acid
• 33
• 3-{4-[3-Chloro-5-(2- pyridin-3-yl-4- trifluoromethyl-phenoxy)- phenoxy]-2-methyl- phenyl}-propionic acid
• 34
• {4-[3-(4-Chloro-2- phenoxy-phenoxy)- phenoxy]-2-methyl- phenylsulfanyl}-acetic acid
• 35
• 2-{4-[3-(4-Chloro-2- phenoxy-phenoxy)- phenoxy]-phenoxy}-2- methyl-propionic acid
• 36
• 2-{4-[3-(4-Chloro-2- phenoxy-phenoxy)- phenoxy]-2-methyl- phenoxy}-2-methyl- propionic acid
• 37
• {4-[3-(4-Chloro-2- phenoxy-phenoxy)- phenoxy]-2-methyl- phenoxy}-acetic acid
• 38
• 3-{4-[3-(4-Chloro-2- phenoxy-phenoxy)- phenoxy]-2-fluoro- phenyl}-propionic acid
• 39
• 4-{4-[3-(4-Chloro-2- phenoxy-phenoxy)- phenoxy]-2-methyl- phenyl}-butyric acid
• 40
• 3-{4-[3-(4-Chloro-2- phenoxy-phenoxy)- phenoxy]-2-ethyl-phenyl}- propionic acid
• 41
• 3-{4-[3-(2-Benzyl-4- chloro-phenoxy)- phenoxy]-2-methyl- phenyl}-propionic acid
• 42
• 3-{4-[3-(2-Benzyl-4- chloro-phenoxy)-5- methyl-phenoxy]-2- methyl-phenyl}-propionic acid
• 43
• 3-{4-[3-(4-Chloro-2- cyclohexyl-phenoxy)-5- methyl-phenoxy]-2- methyl-phenyl}-propionic acid
• 44
• 3-{4-[3-(2-Benzyl-4- chloro-phenoxy)-5-fluoro- phenoxy]-2-methyl- phenyl}-propionic acid
• 45
• 3-{2-Methyl-4-[3-methyl- 5-(3-phenoxy-5- trifluoromethyl-pyridin-2- yloxy)-phenoxy]-phenyl}- propionic acid.