GPR120 agonists for the treatment of type II diabetes

Patent metadata

Field	Value
Publication number	US-10118922-B2
Application number	US-201414200108-A
Country	US
Kind code	B2
Filing date	Mar 7, 2014
Priority date	Mar 14, 2013
Publication date	Nov 6, 2018
Grant date	Nov 6, 2018

Abstract

Disclosed are compounds, compositions and methods for treating of disorders that are affected by the modulation of the GPR120 receptor. Such compounds are represented by Formula (I) and Formula (II) as follows:

wherein Y, R 1 , G, and Q are defined herein;

and

wherein R 11 , R 21 , R 41 , R B1 and G 1 , are defined herein.

First claim

The invention claimed is:

1. A compound of Formula (I)

wherein
Y is C(R 3 ) or N; wherein R 3 is hydrogen or methyl;
R 1 is selected from the group consisting of hydrogen, C 1-4 alkyl, fluoro, chloro, cyclopropyl, 1,1-difluoroethyl, perfluoroethyl, trifluoromethyl, and phenyl; wherein phenyl is optionally independently substituted with one or two substituents that are C 1-2 alkyl, methoxy, chloro, fluoro, or trifluoromethyl;
Q is q1

wherein
R B is one to four substituents independently selected from the group consisting of methyl, ethyl, methoxy, fluoro, chloro, bromo, trifluoromethyl, and trifluoromethoxy; provided that R B is no more than one of ethyl, methoxy, bromo, trifluoromethyl, or trifluoromethoxy;
R C is
i)

wherein the bond between C 1 and C 2 is a single bond or double bond;
R 2 is hydroxymethyl or carboxy;
R 4 is hydrogen or methyl;
ii) hydroxymethylethynyl;
iii) carboxycyclopropyl; or
iv) hydroxymethylcyclopropyl;

G is
4-(R A )phenyl, wherein R A is selected from the group consisting of hydrogen, ethynyl, C 1-3 alkyl, C 1-2 alkoxy, fluoro, chloro, bromo, 1-fluoroethyl, 1,1-difluoroethyl, trifluoromethyl, methylcarbonyl, and cyclopropyl;
wherein said phenyl of group xiii) is optionally independently further substituted with one or two additional fluoro or methoxy substituents;

or an enantiomer, diastereomer, or pharmaceutically acceptable salt form thereof.

2. The compound of claim 1 wherein Y is C(R 3 ) wherein R 3 is hydrogen or methyl.

3. The compound of claim 1 wherein Y is N.

4. The compound of claim 1 wherein R 1 is selected from the group consisting of hydrogen, C 1-2 alkyl, fluoro, chloro, cyclopropyl, perfluoroethyl, trifluoromethyl, and phenyl; wherein phenyl is optionally independently substituted with one or two substituents that are C 1-2 alkyl, methoxy, chloro, or fluoro.

5. The compound of claim 4 wherein R 1 is selected from the group consisting of hydrogen, methyl, trifluoromethyl, and phenyl; wherein phenyl is optionally independently substituted with one or two substituents that are methyl, methoxy, chloro, or fluoro.

6. The compound of claim 1 wherein Q is q1

wherein
R B is one to four substituents independently selected from the group consisting of methyl, ethyl, fluoro, chloro, bromo, trifluoromethyl, and trifluoromethoxy; provided that R B is no more than one of ethyl, bromo, trifluoromethyl, or trifluoromethoxy;
R C is
i)

wherein the bond between C 1 and C 2 is a single bond or double bond;
R 2 is hydroxymethyl or carboxy;
R 4 is hydrogen or methyl; or

ii) carboxycyclopropyl.

7. The compound of claim 6 wherein Q is q1

wherein
R B is one to four substituents independently selected from the group consisting of methyl, fluoro, and bromo; provided that R B is no more than one of bromo;
R C is

wherein the bond between C 1 and C 2 is a single bond;
R 2 is hydroxymethyl or carboxy;
R 4 is hydrogen or methyl.

8. The compound of claim 7 wherein Q is q1

wherein
R B is one to four substituents independently selected from the group consisting of methyl, fluoro, and bromo; provided that R B is no more than one of bromo;
R C is

wherein the bond between C 1 and C 2 is a single bond;
R 2 is hydroxymethyl or carboxy;
R 4 is hydrogen or methyl.

9. The compound of claim 8 wherein R C is

wherein the bond between C 1 and C 2 is a single bond;
R 2 is carboxy;
R 4 is hydrogen.

10. The compound of claim 1 wherein G is
4-(R A )phenyl, wherein R A is selected from the group consisting of hydrogen, ethynyl, C 1-2 alkyl, C 1-2 alkoxy, fluoro, chloro, bromo, 1-fluoroethyl, 1,1-difluoroethyl, trifluoromethyl, methylcarbonyl, and cyclopropyl;
wherein said phenyl of group xi) is optionally independently further substituted with one or two additional fluoro or methoxy substituents.

11. The compound of claim 10 wherein G is
4-(R A )phenyl, wherein R A is selected from the group consisting of hydrogen, C 1-2 alkyl, methoxy, chloro, trifluoromethyl, and methylcarbonyl;
wherein said phenyl of group ix) is optionally independently further substituted with one or two additional fluoro substituents.

12. A compound of Formula (I)

wherein
Y is N or C(R 3 ), wherein R 3 is hydrogen or methyl;
R 1 is selected from the group consisting of hydrogen, C 1-2 alkyl, fluoro, chloro, cyclopropyl, perfluoroethyl, trifluoromethyl, and phenyl; wherein phenyl is optionally independently substituted with one or two substituents that are C 1-2 alkyl, methoxy, chloro, or fluoro;
Q is q1

wherein
R B is one to four substituents independently selected from the group consisting of methyl, ethyl, fluoro, chloro, bromo, trifluoromethyl, and trifluoromethoxy; provided that R B is no more than one of ethyl, bromo, trifluoromethyl, or trifluoromethoxy;
R C is
i)

wherein the bond between C 1 and C 2 is a single bond or double bond;
R 2 is hydroxymethyl or carboxy;
R 4 is hydrogen or methyl; or

ii) carboxycyclopropyl;
G is
4-(R A )phenyl, wherein R A is selected from the group consisting of hydrogen, ethynyl, C 1-2 alkyl, C 1-2 alkoxy, fluoro, chloro, bromo, 1-fluoroethyl, 1,1-difluoroethyl, trifluoromethyl, methylcarbonyl, and cyclopropyl;
wherein said phenyl of group xi) is optionally independently further substituted with one or two additional fluoro or methoxy substituents;

or an enantiomer, diastereomer, or pharmaceutically acceptable salt form thereof.

13. A compound of Formula (I)

wherein
Y is N or C(R 3 ), wherein R 3 is hydrogen or me

Assignees

• Janssen Pharmaceutica Nv

Inventors

• Sui Zhihua
• Cai Chaozhong
• Zhang Xuqing

Classifications

• A61P3/10

  for hyperglycaemia, e.g. antidiabetics · CPC title

• A61P3/06

  Antihyperlipidemics · CPC title

• A61P43/00

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

• A61P3/04

  Anorexiants; Antiobesity agents · CPC title

• C07D409/04

  directly linked by a ring-member-to-ring-member bond · CPC title