Phenoxy acetic acids and phenyl propionic acids as PPAR delta agonists
Phenoxy acetic acids and phenyl propionic acids and their use in improving mitochondrial energy output in a subject are provided herein. The present compounds are activators of PPARδ and may be useful for treating conditions mediated by the same.
1. A process for the preparation of a compound of the following formula:
or a pharmaceutically acceptable salt thereof,
comprising saponification of a compound of formula (I):
or a salt thereof, wherein:
is a double bond, with either E or Z substitution;
X 1 is C 1-6 alkyl substituted with morpholino;
X 2 is phenylene;
X 3 is phenyl substituted with one or more halogens;
Ar is phenylene optionally substituted with methyl;
Y 1 is O;
Y 2 is O;
Z is CH 2 ;
R 1 is hydrogen; and
R 2 is C 1-6 alkyl.
2. The process of claim 1 , wherein X 1 is morpholin-4-ylmethyl.
3. The process of claim 2 , wherein R 2 is methyl or ethyl.
4. The process of claim 1 , wherein the compound of formula (I) is methyl (Z)-[4-[3-(4-fluorophenyl)-3-[4-[3-(morpholin-4-yl) propynyl]phenyl]allyloxy]-2-methylphenoxy]acetate, or a salt thereof.
5. The process of claim 1 , wherein the compound of formula (I) is methyl (E)-[4-[3-(4-fluorophenyl)-3-[4-[3-(morpholin-4-yl) propynyl]phenyl]allyloxy]-2-methylphenoxy]acetate, or a salt thereof.