4-(phenoxyalkyl)thio)-phenoxyacetic acids and analogs

Patent metadata

Field	Value
Publication number	US-9724322-B2
Application number	US-201615074125-A
Country	US
Kind code	B2
Filing date	Mar 18, 2016
Priority date	Sep 19, 2003
Publication date	Aug 8, 2017
Grant date	Aug 8, 2017

Abstract

The invention features 4-((phenoxyalkyl)thio)-phenoxyacetic acids and analogs, compositions containing them, and methods of using them as PPAR delta modulators to treat or inhibit the progression of, for example, dyslipidemia.

First claim

The invention claimed is:

1. A method for treating or inhibiting the progression of a PPAR-delta mediated condition, said method comprising administering to a patient in need of treatment a pharmaceutically effective amount of Formula (II):

wherein
X is selected from a covalent bond, S or O;
Y is S or O;
- - - - - W - - - - - represents a group selected from —CH═, —CH 2 —, —CH 2 —CH 2 —, —CH 2 —CH═, and —CH═CH—;

Z is selected from O, CH, and CH 2 , provided when Y is O, Z is O;
R 1 and R 2 are independently selected from H, C 1-3 alkyl, C 1-3 alkoxy, halo, and NR a R b wherein R a and R b are independently H or C 1-3 alkyl;
R 3 and R 4 are independently selected from H, halo, cyano, hydroxy, acetyl, C 1-5 alkyl, C 1-4 alkoxy, and NR c R d wherein R c and R d are independently H or C 1-3 alkyl, provided that R 3 and R 4 are not both H;

n is 1 or 2;

or a pharmaceutically acceptable salt thereof.

2. The method of claim 1 wherein the compound is selected from the group consisting of
acetic acid, {4-[(2R)-2-hydroxy-3-(4-trifluoromethyl-phenoxy)-propylsulfanyl]-2-methyl-phenoxy}-; and
acetic acid, {4-[(2S)-2-hydroxy-3-(4-trifluoromethyl-phenoxy)-propylsulfanyl]-2-methyl-phenoxy}.

3. The method of claim 1 , wherein the compound is acetic acid, {4-[(2R)-2-hydroxy-3-(4-trifluoromethyl-phenoxy)-propylsulfanyl]-2-methyl-phenoxy}-.

4. The method of claim 1 , wherein the compound is acetic acid, {4-[(2S)-2-hydroxy-3-(4-trifluoromethyl-phenoxy)-propylsulfanyl]-2-methyl-phenoxy}-.

5. The method of claim 1 , wherein the PPAR-delta mediated condition is selected from the group consisting of diabetes, cardiovascular diseases, Metabolic X Syndrome, hypercholesterolemia, hypo-HDL-cholesterolemia, hyper-LDL-cholesterolemia, dyslipidemia, artherosclerosis, and obesity.

6. The method of claim 5 , wherein the compound is selected from the group consisting of acetic acid, {4-[(2R)-2-hydroxy-3-(4-trifluoromethyl-phenoxy)-propylsulfanyl]-2-methyl-phenoxy}-; and
acetic acid, {4-[(2S)-2-hydroxy-3-(4-trifluoromethyl-phenoxy)-propylsulfanyl]-2-methyl-phenoxy}.

Assignees

• Janssen Pharmaceutica Nv
• Janssen Pharmaceutica Nv

Inventors

• Kuo Gee-Hong
• Zhang Rui
• Wang Aihua
• Deangelis Alan R

Classifications

• A61P9/10

  for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis · CPC title

• A61P3/06

  Antihyperlipidemics · CPC title

• A61P9/12

  Antihypertensives · CPC title

• A61P9/00

  Drugs for disorders of the cardiovascular system · CPC title

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title