Aromatic ring compound

Patent metadata

Field	Value
Publication number	US-9382188-B2
Application number	US-201314377953-A
Country	US
Kind code	B2
Filing date	Feb 12, 2013
Priority date	Feb 13, 2012
Publication date	Jul 5, 2016
Grant date	Jul 5, 2016

Abstract

Provided is an aromatic ring compound having a GPR40 agonist activity. A compound represented by the formula (I):

wherein each symbol is as described in the DESCRIPTION, or a salt thereof has a GPR40 agonist activity, and is useful as an agent for the prophylaxis or treatment of diabetes and the like.

First claim

The invention claimed is:

1. A compound of formula (I):

wherein:
ring A is a benzene ring or a pyridine ring, each of which is optionally further substituted by 1 to 3 halogen atoms or a C 1-6 alkoxy group;
ring B is a benzene ring or a pyridine ring, wherein ring A and —X are attached at the 1,4-positions of ring B relative to each other;
ring C is a benzene ring, a pyridine ring or a pyrimidine ring, wherein —CH 2 —X and —Y are attached at the 1,3-postions of ring C relative to each other;
X is —NH—, —N(methyl)-, —N(trifluoroethyl)-, —N(acetyl)-, —CHF—, —O—, —S—, —S(O)— or —S(O) 2 —;
Y is —CR 6B R 6C — or —O— wherein R 6B and R 6C are each independently (1) a C 37 cycloalkyl group optionally substituted by 1 to 3 substituents selected from the group consisting of a halogen atom and cyano, (2) a hydrogen atom, (3) a C 1-6 alkyl group optionally substituted by 1 to 3 substituents selected from the group consisting of a halogen atom, a C 3-7 cycloalkyl group, cyano, carboxyl, a C 1-6 alkoxy-carbonyl group, and a carbamoyl group, (4) a C 2-6 alkenyl group optionally substituted by a halogen atom, or (5) a C 2-6 alkenyl group optionally substituted by 1 to 3 substituents selected from the group consisting of a halogen atom and a C 3-7 cycloalkyl group;
R 1 is (1) a C 1-6 alkoxy group optionally substituted by a halogen atom, (2) a C 1-8 alkyl group, (3) hydroxy, (4) carboxyl, (5) a C 1-6 alkyl-sulfonyl-amino group, (6) a 5- to 10-membered non-aromatic heterocyclyl-oxy group, (7) a 5-to 10-membered non-aromatic heterocyclyl-sulfonyl group, or (8) cyano;
R 2 is (1) a C 1-13 alkyl group optionally substituted by 1 to 3 substituents selected from the group consisting of (i) a halogen atom, (ii) hydroxy, (iii) cyano, (iv) a C 1-6 alkoxy group optionally substituted by a C 1-6 alkoxy group, and (v) a C 3-7 cycloalkyl group, (2) hydroxy, (3) a C 1-6 alkoxy group, (4) a C 6-14 aryl group optionally substituted by a C 1-6 alkyl group optionally substituted by 1 to 3 halogen atoms, or (5) a heterocyclic group optionally substituted by 1 to 3 substituents selected from the group consisting of cyano and a C 1-6 alkyl group; and
both R 3 and R 4 are hydrogen atoms, or a salt thereof.

2. 3-Cyclopropyl-3-(3-(((2-(2,2-dimethylpropyl)-2′-fluoro-5′-methoxybiphenyl-4-yl)oxy)methyl)phenyl)propanoic acid or a salt thereof.

3. 3-Cyclopropyl-3-(3-(((6-(2,2-dimethylpropyl)-5-(2-fluoro-5-methoxyphenyl)pyridin-2-yl)oxy)methyl)phenyl)propanoic acid or a salt thereof.

4. 3-Cyclopentyl-3-(3-(((2-(2,2-dimethylpropyl)-2′-fluoro-5′-methoxybiphenyl-4-yl)oxy)methyl)phenyl)propanoic acid or a salt thereof.

5. A pharmaceutical composition comprising the compound according to claim 1 or a salt thereof, and a pharmacologically acceptable carrier.

6. The pharmaceutical composition according to claim 5 , which is a GPR40 receptor function modulator.

7. The pharmaceutical composition according to claim 5 , which is a therapeutic agent for treating type 2 diabetes.

8. A method for the treatment of type 2 diabetes in a mammal, comprising administering an effective amount of the compound according to claim 1 or a salt thereof to the mammal.

9. A method of modulating a GPR40 receptor function in a mammal, comprising administering an effective amount of the compound according to claim 1 or a salt thereof to the mammal.

10. The compound according to claim 1 or a salt thereof for use in the treatment of type 2 diabetes.

Assignees

• Takeda Pharmaceutical

Inventors

• Miwatashi Seiji
• Suzuki Hideo
• Okawa Tomohiro
• Miyamoto Yasufumi
• Yamasaki Takeshi
• Hitomi Yuko
• Hirata Yasuhiro
• Shibuya Akito

Classifications

• C07C59/72

  containing six-membered aromatic rings and other rings · CPC title

• C07D231/12

  with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms · CPC title

• C07D213/68

  attached in position 4 · CPC title

• C07C229/34

  the carbon skeleton containing six-membered aromatic rings · CPC title

• C07C317/44

  having sulfone or sulfoxide groups and carboxyl groups bound to the same carbon skeleton · CPC title