Phenoxy acetic acids and phenyl propionic acids as PPAR delta agonists

Patent metadata

Field	Value
Publication number	US-10947180-B2
Application number	US-201916679026-A
Country	US
Kind code	B2
Filing date	Nov 8, 2019
Priority date	Dec 22, 2005
Publication date	Mar 16, 2021
Grant date	Mar 16, 2021

Abstract

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.

First claim

The invention claimed is:

1. A compound of formula (I) or a pharmaceutically acceptable 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 compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein X 1 is morpholin-4-ylmethyl.

3. The compound of claim 2 , or a pharmaceutically acceptable salt thereof, wherein R 2 is methyl or ethyl.

4. A pharmaceutically acceptable salt of a compound of formula (I):

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.

5. The pharmaceutically acceptable salt of claim 4 , wherein X 1 is morpholin-4-ylmethyl.

6. The pharmaceutically acceptable salt of claim 5 , wherein R 2 is methyl or ethyl.

7. The pharmaceutically acceptable salt of claim 1 , wherein the pharmaceutically acceptable salt is an acid addition salt.

8. The pharmaceutically acceptable salt of claim 1 , wherein the pharmaceutically acceptable salt is an hydrochloric acid addition salt.

9. A compound that is:
methyl (E)-[4-[3-(4-fluorophenyl)-3-[4-[3-(morpholin-4-yl)propynyl]phenyl]allyloxy]-2-methyl-phenoxy]acetate; or
methyl (Z)-[4-[3-(4-fluorophenyl)-3-[4-[3-(morpholin-4-yl)propynyl]phenyl]allyloxy]-2-methylphenoxy]acetate;
or a pharmaceutically acceptable salt thereof.

10. The compound of claim 1 , wherein the compound is methyl (Z)-[4-[3-(4-fluorophenyl)-3-[4-[3-(morpholin-4-yl)propynyl]phenyl]allyloxy]-2-methylphenoxy]acetate, or a pharmaceutically acceptable salt thereof.

11. The compound of claim 1 , wherein the compound is methyl (E)-[4-[3-(4-fluorophenyl)-3-[4-[3-(morpholin-4-yl)propynyl]phenyl]allyloxy]-2-methyl-phenoxy]acetate, or a pharmaceutically acceptable salt thereof.

Assignees

• Vtv Therapeutics Llc

Inventors

• Sauerberg Per
• Pihera Pavel
• Polivka Zdenek
• Havranek Miroslav
• Petterson Ingrid
• Mogensen John Patrick

Classifications

• A61K31/5377 Primary

  not condensed and containing further heterocyclic rings, e.g. timolol · CPC title

• A61K31/192

  having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid  {(cannabinoids A61K31/658)} · CPC title

• C07C69/736 Primary

  the hydroxy group of the ester being etherified with a hydroxy compound having the hydroxy group bound to a carbon atom of a six-membered aromatic ring · CPC title

• C07C59/68

  the oxygen atom of the ether group being bound to a non-condensed six-membered aromatic ring · CPC title

• C07D409/10

  linked by a carbon chain containing aromatic rings · CPC title