PPAR AGONISTS, COMPOUNDS, PHARMACEUTICAL COMPOSITIONS, AND METHODS OF USE THEREOF

1 . A compound of Formula (I):

or a pharmaceutically acceptable salt thereof,

wherein:

Z is CH, N, or

Ring A is optionally substituted phenylene when Z is CH, optionally substituted pyridinylene when Z is N, or optionally substituted N-oxide pyridinylene when Z is

Ar is optionally substituted 5 or 6-membered monocyclic arylene or heteroarylene, wherein R 2 and

are oriented 1,4 to each other, wherein position 1 is the point of attachment of Ar to ring B; or

Ar is optionally substituted 9- or 10-membered fused bicyclic heteroarylene, wherein R 2 and

are oriented 1,4 to each other, wherein position 1 is the point of attachment of Ar to B, wherein position 1 is the point of attachment of Ar to ring B;

R 1 is —OR 1A or —NR 1A R 1B ;

is 5-membered heterocycloalkylene or heteroarylene optionally substituted with one or more C 1 -C 4 -alkyl, wherein

and Ar are oriented 1,2 to each other, wherein position 1 is the point of attachment of ring B to

R 1 is —OR 1A or —NR 1A R 1B ;

R 1A , R 1B are each independently hydrogen or C 1 -C 4 -alkyl;

W is O, CH 2 , CH═CH, or C≡C;

2 . The compound of claim 1 , wherein the compound has the structure of Formula (II):

or a pharmaceutically acceptable salt thereof,

wherein:

Q 1 is CH═CR 20 , CR 20 ═CH, N═CH, CH═N,

p and t are integers each independently having a value of 1 or 2;

each R 10 is independently hydrogen, halogen, C 1 -C 4 -alkyl, C 1 -C 4 -haloalkyl, CN, C 1 -C 4 -alkoxy, C 1 -C 4 -haloalkoxy, or C 3 -C 6 -cycloalkyl; and

each R 20 is independently hydrogen, halogen, C 1 -C 4 -alkyl, CN, or C 1 -C 4 -alkoxy.

3 . The compound of claim 2 , wherein the compound has the structure of Formula (III):

or a pharmaceutically acceptable salt thereof.

4 - 5 . (canceled)

6 . The compound of claim 1 , wherein the compound has the structure of Formula (VI):

or a pharmaceutically acceptable salt thereof,

wherein:

Q 2 is CR 20 or N;

p and t are integers each independently having a value of 1 or 2;

each R 10 is independently hydrogen, halogen, C 1 -C 4 -alkyl, C 1 -C 4 -haloalkyl, CN, C 1 -C 4 -alkoxy, C 1 -C 4 -haloalkoxy, or C 3 -C 6 -cycloalkyl; and

each R 20 is independently hydrogen, halogen, C 1 -C 4 -alkyl, CN, or C 1 -C 4 -alkoxy.

7 . The compound of claim 6 , wherein the compound has the structure of Formula (VII):

or a pharmaceutically acceptable salt thereof.

8 . The compound of claim 7 , wherein the compound has the structure of Formula (VIII):

or a pharmaceutically acceptable salt thereof.

9 - 17 . (canceled)

18 . The compound of claim 3 , wherein W is O.

19 . The compound of claim 18 , wherein

is selected from the group consisting of:

20 - 23 . (canceled)

24 . The compound of claim 19 , wherein R 2 is phenyl, furanyl, thienyl, OCF 3 , OCHF 2 , or —≡—CF 3 , wherein the phenyl can be optionally substituted with halogen, CN, C 1 -C 4 -alkyl, OH, C 1 -C 4 -alkoxy, formyl, acetyl, acetoxy, or carboxyl, and wherein the furanyl and the thienyl each can be optionally substituted with C 1 -C 4 -alkyl.

25 . (canceled)

26 . The compound of claim 24 , wherein L is selected from the group consisting of:

27 . (canceled)

28 . The compound of claim 24 , wherein L is

29 . The compound of claim 28 , wherein R 10 is hydrogen, halogen, methyl, CN, OCH 3 , cyclopropyl, CF 3 , OCF 3 , or OCHF 2 .

30 . (canceled)

31 . The compound of claim 29 , wherein R 20 is hydrogen or halogen.

32 - 36 . (canceled)

37 . The compound of claim 3 , wherein

W is O;

Z is CH;

R 1 is OH;

L is

R 2 is furanyl or 5-methyl-2-furanyl;

t and p are 1;

R 10 is hydrogen, fluorine, bromine, methyl, or OCH 3 ; and

R 20 is hydrogen, fluorine, or chlorine.

38 . A pharmaceutical composition comprising a pharmaceutically acceptable excipient and the compound of claim 1 , or a pharmaceutically acceptable salt thereof.

39 - 40 . (canceled)

41 . A method of treating a PPARδ related disease or condition in a subject, comprising administering to the subject in need thereof a therapeutically effective amount of one or more compounds of the compound of claim 1 , or a pharmaceutically acceptable salt thereof, or the pharmaceutical composition of comprising the compound of claim 1 and a pharmaceutically acceptable excipient.

42 - 50 . (canceled)