Compounds having activating effect on subtypes of peroxisome proliferator-activated receptors and its preparation method and uses

Patent metadata

Field	Value
Publication number	US-9346770-B2
Application number	US-201113704281-A
Country	US
Kind code	B2
Filing date	Jun 18, 2011
Priority date	Jun 18, 2010
Publication date	May 24, 2016
Grant date	May 24, 2016

Abstract

Phenyl propanoic acid compounds having activating effect on peroxisome proliferator-activated receptors (PPARα,δ,γ) and a preparation method and uses thereof are provided in the present invention. The compounds can be used for treating or preventing diseases associated with peroxisome proliferator-activated receptors (PPARα,δ,γ).

First claim

The invention claimed is:

1. A compound of formula (I) or pharmaceutical acceptable salts thereof:

wherein,
X is O;
Y is O;
R 1 is methyl;
G 1 is ethyl; and
G 2 is H, and G 3 is F.

2. A pharmaceutical composition, comprising the compound according to claim 1 or pharmaceutical acceptable salts thereof.

3. The pharmaceutical composition according to claim 2 , with a dosage form selected from tablets, film-coated tablets, sugar coated tablets, enteric coated tablets, dispersible tablets, capsules, granules, oral solutions and oral suspensions.

4. A method for treatment of diseases associated with α subtype, δ subtype, and γ subtype of peroxisome proliferator-activated receptors in a subject, the method comprising administering to the subject a compound according to claim 1 , and wherein the diseases associated with α subtype, δ subtype, and γ subtype of peroxisome proliferator-activated receptors are selected from hyperglycaemia, insulin resistance, hyperlipidemia and obesity.

5. A method for the preparation of the compound of formula (I) according to claim 1 , including

wherein,
X, Y, R 1 , G 1 , G 2 , and G 3 are as defined in claim 1 , R 3 is a leaving group selected from OH, Cl, Br, I, OTs and OMs.

6. The method according to claim 5 , further comprising heating the compound of formula (III) and the compound of formula (IV) in acetonitrile under reflux in the presence of potassium carbonate; to obtain the compound of formula (II); saponifying the compound of formula (II) in an alcoholic solution in the presence of an alkali; and acidifying the reaction mixture after the reaction is completed; to obtain the compound of formula (I).

7. A method of making a compound of formula (I) or pharmaceutical acceptable salts thereof:

wherein,
X is O, S, NR 11 , or (CR 11 R 11′ ) n , in which n is an integer selected from 1, 2, 3 and 4;
Y is O, S, NR 11 , or (CR 11 R 11′ ) m , in which m is an integer selected from 1, 2, 3 and 4;
R 1 is independently H, methyl or ethyl;
G 1 is ethyl;
G 2 and G 3 are each independently selected from H, alkyl, alkoxy, trifluoromethyl, halogen, nitro, NR 11 R 11′ , alkylthio, amido, cyano, carboxyl and tetrazolyl;
R 11 and R 11′ are each independently selected from H and C 1 -C 6 alkyl, comprising the following steps by reacting compound (III) with compound (IV) to generate compound (II), and then compound (I):

and wherein the compound (III) is prepared according to the following process:

wherein,
X 1 is a leaving group selected from Cl, Br, I, OTs and OMs;
R 2 is a hydroxyl protective group;
R 3 is a leaving group selected from OH, Cl, Br, I, OTs and OMs;
Y is O, S, NR 11 , or (CR 11 R 11′ ) m , in which m is an integer selected from 1, 2, 3 and 4;
R 1 is independently H, methyl or ethyl;
G 2 and G 3 are each independently selected from H, alkyl, alkoxy, trifluoromethyl, halogen, nitro, NR 11 R 11′ , alkylthio, amido, cyano, carboxyl and tetrazolyl; and
R 11 and R 11′ are each independently selected from H and C 1 -C 6 alkyl.

Assignees

• Wang Yaping
• Zheng Guojun
• Sun Peng
• Li Yi
• Wu Yingqiu
• Liu Bin
• Liu Xiaoyu
• Bai Hua
• Li Hongyan
• Zheng Xiaohe
• Zhejiang Hisun Pharm Co Ltd

Inventors

• Wang Yaping
• Zheng Guojun
• Sun Peng
• Li Yi
• Wu Yingqiu
• Liu Bin
• Liu Xiaoyu
• Bai Hua
• Li Hongyan
• Zheng Xiaohe

Classifications

• A61P43/00

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

• A61P3/06

  Antihyperlipidemics · CPC title

• A61P3/10

  for hyperglycaemia, e.g. antidiabetics · CPC title

• A61P5/50

  for increasing or potentiating the activity of insulin · CPC title

• C07D413/10

  linked by a carbon chain containing aromatic rings · CPC title