Novel phenoxuacetic acid derivative, preparation method therefor and uses of derivative as drug

Patent metadata

Field	Value
Publication number	US-2021122704-A1
Application number	US-201816617409-A
Country	US
Kind code	A1
Filing date	May 24, 2018
Priority date	May 27, 2017
Publication date	Apr 29, 2021
Grant date	—

Abstract

The present invention relates to a novel phenoxyacetic acid derivative represented by the general formula (I), preparation method thereof and use of a pharmaceutical composition containing the derivative in preparing a medicament for treating diabetes and metabolic syndrome. The phenoxyacetic acid derivatives have excellent in vivo hypoglycemic activity, which can be used for preventing or treating diabetes.

First claim

What is claimed is:

1 . A compound represented by the formula (I) or a pharmaceutically acceptable salt thereof:

ring A is selected from aryl or heteroaryl;
R 1 , R 2 and R 3 are each independently selected from the group consisting of hydrogen, halogen, hydroxy, cyano, alkyl, alkoxy, wherein the alkyl or alkoxy is optionally further substituted by one or more group selected from the group consisting of halogen, hydroxy, cyano, alkyl and alkoxy;
R 4 is selected from the group consisting of hydrogen and halogen.

2 . The compound represented by the formula (I) or a pharmaceutically acceptable salt thereof according to claim 1 , wherein,
ring A is selected from benzene ring or isoxazole ring; R 1 , R 2 and R 3 are each independently selected from the group consisting of hydrogen, halogen, hydroxy, cyano, alkyl, alkoxy, wherein the alkyl or alkoxy is optionally further substituted by one or more group selected from the group consisting of halogen, hydroxy, cyano, alkyl and alkoxy; R 4 is selected from the group consisting of hydrogen and halogen.

3 . The compound represented by the formula (I) or a pharmaceutically acceptable salt thereof according to claim 2 , wherein,
ring A is selected from benzene ring or isoxazole ring; R 1 , R 2 and R 3 are each independently selected from the group consisting of hydrogen, halogen, hydroxy, cyano, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, wherein said C 1 -C 6 alkyl or C 1 -C 6 alkoxy is optionally substituted by one or more group selected from the group consisting of halogen, hydroxy, cyano, alkyl, alkoxy; said C 1 -C 6 alkyl is selected from the group consisting of methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, tert-butyl, n-pentyl, isopentyl, neopentyl, n-hexyl, isohexyl, cyclohexyl; said C 1 -C 6 alkoxy is selected from the group consisting of methoxy, ethoxy, propoxy, isopropoxy, n-butoxy, isobutoxy, tert-butoxy, n-pentyloxy, isopentyloxy, neopentyloxy, n-hexyloxy, isohexyloxy or cyclohexyloxy; R 4 is selected from hydrogen and F.

4 . The compound represented by the formula (I) or a pharmaceutically acceptable salt thereof according to claim 3 , wherein,
ring A is selected from benzene ring or isoxazole ring; R 1 , R 2 and R 3 are each independently selected from the group consisting of hydrogen, F, Cl, cyano, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, wherein said alkyl or alkoxy is optionally substituted by one or more group selected from the group consisting of F, hydroxy, cyano, C 1 -C 6 alkyl, C 1 -C 6 alkoxy; wherein said C 1 -C 6 alkyl is selected from the group consisting of methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, tert-butyl, n-pentyl, isopentyl, neopentyl, n-hexyl, isohexyl, cyclohexyl; said C 1 -C 6 alkoxy is selected from the group consisting of methoxy, ethoxy, propoxy, isopropoxy, n-butoxy, isobutoxy, tert-butoxy, n-pentyloxy, isopentyloxy, neopentyloxy, n-hexyloxy, isohexyloxy or cyclohexyloxy; R 4 is selected from hydrogen and F.

5 . The compound represented by the formula (I) or a pharmaceutically acceptable salt thereof according to claim 4 , wherein, R 1 , R 2 and R 3 are each independently selected from the group consisting of hydrogen, F, Cl, cyano, C 1 -C 3 alkyl, C 1 -C 3 alkoxy, wherein said C 1 -C 3 alkyl or C 1 -C 3 alkoxy is optionally substituted by one or more group selected from the group consisting of F, hydroxy, cyano, C 1 -C 3 alkyl, C 1 -C 3 alkoxy; wherein said C 1 -C 3 alkyl is selected from the group consisting of methyl, ethyl, propyl and isopropyl; said C 1 -C 3 alkoxy is selected from the group consisting of methoxy, ethoxy, propoxy and isopropoxy.

6 . The compound represented by the formula (I) or a pharmaceutically acceptable salt thereof according to claim 5 , wherein, R 1 , R 2 and R 3 are each independently selected from the group consisting of hydrogen, F, Cl, cyano, C 1 -C 3 alkyl, C 1 -C 3 alkoxy, wherein said C 1 -C 3 alkyl or C 1 -C 3 alkoxy is optionally further substituted by one or more group selected from the group consisting of F, C 1 -C 3 alkyl and C 1 -C 3 alkoxy.

7 . The compound represented by the formula (I) or a pharmaceutically acceptable salt thereof according to claim 6 , wherein,
ring A is selected from benzene ring or:

R 1 is selected from the group consisting of methyl and hydrogen, R 2 is selected from the group consisting of ethoxy, propoxy, methyl, methylsulfonylpropoxy, methoxyethoxy and hydrogen, and R 3 is selected from the group consisting of methyl, trifluoromethyl, F, Cl, isopropyl, cyano, methoxy, hydrogen, and R 4 is selected from the group consisting of hydrogen and F.

8 . The compound represented by the formula (I) or a pharmaceutically acceptable salt thereof according to claim 1 , wherein it is selected from any one of the following compounds:
2-(4-((4′-ethoxy-2′,6′-dimethyl-[1,1′-biphenyl]-3-methylene)amino)-2-fluorophenoxy)acetic acid (I-1); 2-(4-((2′-chloro-[1,1′-biphenyl]-3-methylene)amino)-2-fluorophenoxy)acetic acid (I-2) 2-(4-((2′-methyl-[1,1′-biphenyl]-3-methylene)amino)-2-fluorophenoxy)acetic acid (I-3) 2-(4-((2′-fluoro-[1,1′-biphenyl]-3-methylene)amino)-2-fluorophenoxy)acetic acid (I-4) 2-(4-((2′-chloro-4′-methyl-[1,1′-biphenyl]-3-methylene)amino)-2-fluorophenoxy)acetic acid (I-5) 2-(4-((2′-methoxy-[1,1′-biphenyl]-3-methylene)amino)-2-fluorophenoxy)acetic acid (I-6) 2-(4-((2′-nitrile-[1,1′-biphenyl]-3-methylene)amino)-2-fluorophenoxy)acetic acid (I-7) 2-(4-((2′-trifluoromethyl-[1,1′-biphenyl]-3-methylene)amino)-2-fluorophenoxy)acetic acid (I-8) 2-(4-((4′-propoxy-2′,6′-dimethyl-[1,1′-biphenyl]-3-methylene)amino)-2-fluorophenoxy)acetic acid (I-9); 2-(2-fluoro-4-((4′-(2-methoxyethoxy)-2′,6′-dimethyl-[1,1′-biphenyl]-3-methylene)amino)phenoxy)acetic acid (I-10) 2-(4-(([1,1′-biphenyl]-3-methylene)amino)-2-fluorophenoxy)acetic acid (I-11) 2-(4-((2′,6′-dimethyl-4′-(3-(methylsulfonyl)propoxy)-[1,1′-biphenyl]-3-methylene)amino)-2-fluorophenoxy)acetic acid (I-12) 2-(4-((4′-ethoxy-2′-methyl-[1,1′-biphenyl]-3-yl)methylene)amino)-2-fluorophenoxy)acetic acid (I-13) 2-(4-((3-(3,5-dimethylisoxazol-4-yl)benzyl)amino)-2-fluorophenoxy)acetic acid (I-14) 2-(4-((4′-propoxy-2′-methyl-[1,1′-biphenyl]-3-yl)methylene)amino)-2-fluorophenoxy)acetic acid (I-15) 2-(2-fluoro-4-(((2′-isopropyl-[1,1′-biphenyl]-3-methylene)amino)phenoxy)acetic acid (I-16) 2-(4-((4′-ethoxy-2′,6′-dimethyl-[1,1′-biphenyl]-3-methylene)amino)phenoxy)acetic acid (I-17) 2-(4-((4′-methoxy-2′,6′-dimethyl-[1,1′-biphenyl]-3-methylene)amino)phenoxy)acetic acid (I-18) 2-(4-(((4′-methoxy-2′-methyl-[1,1′-biphenyl]-3-yl)methylene)amino)-2-fluorophenoxy)acetic acid (I-19) 2-(4-((4′-methoxy-2′,6′-dimethyl-[1,1′-biphenyl]-3-methylene)amino)-2-fluorophenoxy)acetic acid (I-20) 2-(4-((4′-methoxy-2′-methyl-[1,1′-biphenyl]-3-yl)methylene)amino)phenoxy)acetic acid (I-21) 2-(4-(((4′-isopropoxy-2′-methyl-[1,1′-biphenyl]-3-yl)methylene)amino)-2-fluorophenoxy)acetic acid (I-22) 2-(4-(((4′-isopropoxy-2′-methyl-[1,1′-biphenyl]-3-yl)methylene)amino)phenoxy)acetic acid (I-23) 2-(4-((2′-chloro-[1,1′-biphenyl]-3-methylene)amino)phenoxy)acetic acid (I-24) 2-(4-((2′-methyl-[1,1′-biphenyl]-3-methylene)amino)phenoxy)acetic acid (I-25) 2-(4-((2′-fluoro-[1,1′-biphenyl]-3-methylene)amino)phenoxy)acetic acid (I-26) 2-(4-((2′-chloro-4′-methyl-[1,1′-biphenyl]-3-methylene)amino)phenoxy)acetic acid (I-27) 2-(4-((2′-trifluoromethyl-[1,1′-biphenyl]-3-methylene)amino)phenoxy)acetic acid (I-28) 2-(4-((4′-trifluoromethoxy-2′,6′-dimethyl-[1,1′-biphenyl]-3-methylene)amino)phenoxy)

Assignees

• Univ China Pharma

Inventors

• Qian Hai
• Huang Wenlong
• Liu Chunxia
• Yang Jianyong

Classifications

• C07C217/84 Primary

  the oxygen atom of at least one of the etherified hydroxy groups being further bound to an acyclic carbon atom · CPC title

• C07C255/58

  containing cyano groups and singly-bound nitrogen atoms, not being further bound to other hetero atoms, bound to the carbon skeleton · CPC title

• C07D261/08

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

• C07C317/18

  with sulfone or sulfoxide groups bound to acyclic carbon atoms of the carbon skeleton · CPC title

• C07C255/59

  the carbon skeleton being further substituted by singly-bound oxygen atoms · CPC title