IP Library › Granted Patent US 11,261,186

Granted Patent B2

US 11,261,186 · App. 15/539,310 · Granted Mar 1, 2022

Biaryl derivative as GPR120 agonist

Inventors: Young Kwan Kim (Daejeon, KR); Sang Yun Park (Daejeon, KR); Hyun Woo Joo (Daejeon, KR); Eun Sil Choi (Daejeon, KR); Seung Yup Paek (Daejeon, KR); Seung Wan Kang (Daejeon, KR); Byung Gyu Kim (Daejeon, KR); Chang Seok Lee (Daejeon, KR); Sung Wook Kim (Daejeon, KR); Sang Dae Lee (Daejeon, KR)

Assignee: LG CHEM. LTD.

C07D487/04 A61K31/4725 C07C59/31 C07C229/42 C07C229/44 C07C317/22 C07D207/06 C07D209/08 C07D211/34 C07D213/30 C07D213/64 C07D213/70 C07D231/56 C07D235/16 C07D239/34 C07D241/18 C07D261/08 C07D277/34 C07D307/42 C07D307/80 C07D311/58 C07D317/46 C07D317/72 C07D333/16 C07D401/04 C07D401/10 C07D401/12 C07D401/14 C07D405/04 C07D405/12 C07D405/14 C07D407/04 C07D409/04 C07D409/10 C07D409/14 C07D413/10 C07D413/12 C07D417/10 C07C2601/04 C07C2601/08

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Quick Facts

Patent No.: US 11,261,186
App. No.: 15/539,310
Granted: Mar 1, 2022
Kind: B2

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Abstract

Compounds having the chemical formula 1, a method for producing the compounds of chemical formula 1, a pharmaceutical composition comprising same, and use thereof as a GPR120 agonist for prevention or treatment of inflammation or metabolic diseases such as diabetes, complications from diabetes, obesity, non-alcoholic fatty liver disease, fatty liver disease, and osteoporosis.

Claims (138)

1. A compound selected from the group consisting of:

2-[1-[4-[4-(cyclobutoxy)-6-methyl-pyrimidin-2-yl]-2,6-difluoro-phenyl]-4-piperidyl]acetic acid,

2-[1-[4-[2-(cyclobutoxy)-6-methyl-pyrimidin-4-yl]-2,6-difluoro-phenyl]-4-piperidyl]acetic acid,

2-[1-[4-[4-(cyclobutoxy)-6-methyl-pyrimidin-2-yl]-2,6-difluoro-phenyl]azetidin-3-yl]acetic acid,

2-[1-[4-[6-(cyclobutoxy)pyrazin-2-yl]-2,6-difluoro-phenyl]-4-piperidyl]acetic acid,

2-[1-[4-[4-(cyclobutoxy)pyrimidin-2-yl]-2,6-difluoro-phenyl]-4-piperidyl]acetic acid,

2-[1-[4-[4-(cyclopropylmethoxy)-6-methyl-pyrimidin-2-yl]-2,6-difluoro-phenyl]-4-piperidyl]acetic acid,

2-[1-[4-[4-(cyclopropylmethoxy)pyrimidin-2-yl]-2,6-difluoro-phenyl]-4-piperidyl]acetic acid,

2-[1-[4-[6-(cyclopropylmethoxy)pyrazin-2-yl]-2,6-difluoro-phenyl]-4-piperidyl]acetic acid,

2-[1-[4-[6-(cyclobutoxy)pyrazin-2-yl]-2,6-difluoro-phenyl]azetidin-3-yl]acetic acid,

2-[1-[4-[6-(cyclopropylmethoxy)pyrazin-2-yl]-2,6-difluoro-phenyl]azetidin-3-yl]acetic acid,

2-[1-[4-[4-(cyclobutoxy)pyrimidin-2-yl]-2,6-difluoro-phenyl]azetidin-3-yl]acetic acid,

2-[1-[4-[4-(cyclopropylmethoxy)pyrimidin-2-yl]-2,6-difluoro-phenyl]azetidin-3-yl]acetic acid,

2-[1-[4-(6-ethoxypyrazin-2-yl)-2,6-difluoro-phenyl]-4-piperidyl]acetic acid,

2-[1-[2,6-difluoro-4-(6-isopropoxypyrazin-2-yl)phenyl]-4-piperidyl]acetic acid,

2-[1-[2,6-difluoro-4-(6-methoxypyrazin-2-yl)phenyl]-4-piperidyl]acetic acid,

2-[1-[2,6-difluoro-4-(6-propoxypyrazin-2-yl)phenyl]-4-piperidyl]acetic acid,

2-[1-[2,6-difluoro-4-(6-isobutoxypyrazin-2-yl)phenyl]-4-piperidyl]acetic acid,

2-[1-[4-(6-butoxypyrazin-2-yl)-2,6-difluoro-phenyl]-4-piperidyl]acetic acid,

2-[1-[4-[6-(cyclopentoxy)pyrazin-2-yl]-2,6-difluoro-phenyl]-4-piperidyl]acetic acid,

2-[1-[4-(4-ethoxypyrimidin-2-yl)-2,6-difluoro-phenyl]-4-piperidyl]acetic acid,

2-[1-[2,6-difluoro-4-(4-isopropoxypyrimidin-2-yl)phenyl]-4-piperidyl]acetic acid,

2-[1-[2,6-difluoro-4-(4-propoxypyrimidin-2-yl)phenyl]-4-piperidyl]acetic acid,

2-[1-[2,6-difluoro-4-(4-isobutoxypyrimidin-2-yl)phenyl]-4-piperidyl]acetic acid,

2-[1-[4-(4-ethoxy-6-methyl-pyrimidin-2-yl)-2,6-difluoro-phenyl]-4-piperidyl]acetic acid,

2-[1-[2,6-difluoro-4-(4-isopropoxy-6-methyl-pyrimidin-2-yl)phenyl]-4-piperidyl]acetic acid,

2-[1-[2,6-difluoro-4-(4-methyl-6-propoxy-pyrimidin-2-yl)phenyl]-4-piperidyl]acetic acid,

2-[1-[2,6-difluoro-4-(4-isobutoxy-6-methyl-pyrimidin-2-yl)phenyl]-4-piperidyl]acetic acid,

2-[1-[2,6-difluoro-4-(6-pyrrolidin-1-ylpyrazin-2-yl)phenyl]-4-piperidyl]acetic acid,

2-[1-[2,6-difluoro-4-[6-(isopropylamino)pyrazin-2-yl]phenyl]-4-piperidyl]acetic acid,

2-[1-[4-[6-(diethylamino)pyrazin-2-yl]-2,6-difluoro-phenyl]-4-piperidyl]acetic acid,

2-[1-[2,6-difluoro-4-[6-(isobutylamino)pyrazin-2-yl]phenyl]-4-piperidyl]acetic acid,

2-[1-[4-[6-(cyclopentylamino)pyrazin-2-yl]-2,6-difluoro-phenyl]-4-piperidyl]acetic acid,

2-[1-[4-[6-(dimethylamino)pyrazin-2-yl]-2,6-difluoro-phenyl]-4-piperidyl]acetic acid,

2-[1-[2,6-difluoro-4-[4-(isobutylamino)pyrimidin-2-yl]phenyl]-4-piperidyl]acetic acid,

2-[1-[4-[6-(cyclobutoxy)-5-methyl-pyrazin-2-yl]-2,6-difluoro-phenyl]-4-piperidyl]acetic acid,

2-[1-[2,6-difluoro-4-(6-phenylpyrazin-2-yl)phenyl]-4-piperidyl]acetic acid,

2-[1-[4-(6-cyclopentylpyrazin-2-yl)-2,6-difluoro-phenyl]-4-piperidyl]acetic acid,

2-[1-[2,6-difluoro-4-(6-isobutylpyrazin-2-yl)phenyl]-4-piperidyl]acetic acid,

2-[1-[2,6-difluoro-4-(4-isobutylpyrimidin-2-yl)phenyl]-4-piperidyl]acetic acid,

2-[1-[4-(6-butylpyrazin-2-yl)-2,6-difluoro-phenyl]-4-piperidyl]acetic acid,

2-[1-[2,6-difluoro-4-(6-isopentylpyrazin-2-yl)phenyl]-4-piperidyl]acetic acid,

2-[1-[4-[4-(cyclobutoxy)-5-fluoro-pyrimidin-2-yl]-2,6-difluoro-phenyl]-4-piperidyl]acetic acid,

2-[1-[4-[4-(cyclopropylmethoxy)-5-fluoro-pyrimidin-2-yl]-2,6-difluoro-phenyl]-4-piperidyl]acetic acid,

2-[1-[4-(6-cyclobutylpyrazin-2-yl)-2,6-difluoro-phenyl]-4-piperidyl]acetic acid,

2-[1-[4-[4-(cyclobutoxy)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl]-2,6-difluoro-phenyl]-4-piperidyl]acetic acid,

2-[1-[4-[4-(cyclobutoxy)-5,6-dimethyl-pyrimidin-2-yl]-2,6-difluoro-phenyl]-4-piperidyl]acetic acid,

4-[2-chloro-4-[4-(cyclobutoxy)-6-methyl-pyrimidin-2-yl]-6-fluoro-phenoxy]butanoic acid,

4-[2-chloro-4-[2-(cyclobutoxy)-6-methyl-pyrimidin-4-yl]-6-fluoro-phenoxy]butanoic acid,

4-[2-chloro-4-[4-(cyclopropylmethoxy)-6-methyl-pyrimidin-2-yl]-6-fluoro-phenoxy]butanoic acid,

4-[4-[6-(cyclobutoxy)pyrazin-2-yl]-2,6-difluoro-phenoxy]butanoic acid,

5-[4-[6-(cyclobutoxy)pyrazin-2-yl]-2,6-difluoro-phenyl]hexanoic acid,

5-[4-(2-cyclobutoxy-6-methyl-pyrimidin-4-yl)-2,6-difluoro-phenyl]-hexanoic acid,

5-[4-(4-cyclobutoxy-6-methyl-pyrimidin-2-yl)-2,6-difluoro-phenyl]-hexanoic acid,

4-[4-(4-cyclobutoxy-pyrimidin-2-yl)-2,6-difluoro-phenoxy]-butyric acid,

4-[4-(2-cyclobutoxy-pyrimidin-4-yl)-2,6-difluoro-phenoxy]-butyric acid,

4-[2-chloro-4-(4-cyclobutoxy-pyrimidin-2-yl)-6-fluoro-phenoxy]-butyric acid,

4-[2-chloro-4-(2-cyclobutoxy-pyrimidin-4-yl)-6-fluoro-phenoxy]-butyric acid,

4-[4-(4-cyclobutoxy-6-methyl-pyrimidin-2-yl)-2,6-difluoro-phenoxy]-butyric acid,

4-[2-chloro-4-(4-cyclopropylmethoxy-pyrimidin-2-yl)-6-fluoro-phenoxy]-butyric acid,

4-[2-chloro-4-(6-cyclobutoxy-pyrazin-2-yl)-6-fluoro-phenoxy]-butyric acid,

4-[2-chloro-4-(6-cyclopropylmethoxy-pyrazin-2-yl)-6-fluoro-phenoxy]-butyric acid,

4-[4-(4-cyclopropylmethoxy-6-methyl-pyrimidin-2-yl)-2,6-difluoro-phenoxy]-butyric acid,

4-[4-(4-cyclopropylmethoxy-pyrimidin-2-yl)-2,6-difluoro-phenoxy]-butyric acid,

4-[4-(6-cyclopropylmethoxy-pyrazin-2-yl)-2,6-difluoro-phenoxy]-butyric acid,

4-[2-chloro-6-fluoro-4-(6-isopropoxy-pyrazin-2-yl)-phenoxy]-butyric acid,

4-[2-chloro-4-(6-ethoxy-pyrazin-2-yl)-6-fluoro-phenoxy]-butyric acid,

4-[4-[4-(cyclobutoxy)-6-methyl-pyrimidin-2-yl]-2,6-difluoro-N-methyl-anilino]butanoic acid,

4-[4-[4-(cyclobutoxy)pyrimidin-2-yl]-2,6-difluoro-N-methyl-anilino]butanoic acid,

4-[4-[6-(cyclobutoxy)pyrazin-2-yl]-2,6-difluoro-N-methyl-anilino]butanoic acid,

4-[4-[4-(cyclopropylmethoxy)-6-methyl-pyrimidin-2-yl]-2,6-difluoro-N-methyl-anilino]butanoic acid,

4-[4-[4-(cyclopropylmethoxy)pyrimidin-2-yl]-2,6-difluoro-N-methyl-anilino]butanoic acid,

4-[4-[6-(cyclopropylmethoxy)pyrazin-2-yl]-2,6-difluoro-N-methyl-anilino]butanoic acid,

2-{1-[2,6-difluoro-4-(6-propoxy-pyrazin-2-yl)phenyl]pyrrolidin-3-yl}acetic acid,

2-{1-[2,6-difluoro-4-(6-isobutoxy-pyrazin-2-yl)phenyl]pyrrolidin-3-yl}acetic acid,

2-{1-[2,6-difluoro-4-(6-cyclopentoxy-pyrazin-2-yl)phenyl]pyrrolidin-3-yl}acetic acid,

2-{1-[2,6-difluoro-4-(6-butoxy-pyrazin-2-yl)phenyl]pyrrolidin-3-yl}acetic acid,

2-{1-[2,6-difluoro-4-(4-propoxy-pyrimidin-2-yl)phenyl]pyrrolidin-3-yl}acetic acid,

2-{1-[2,6-difluoro-4-(4-isopropoxy-pyrimidin-2-yl)phenyl]pyrrolidin-3-yl}acetic acid,

2-{1-[2,6-difluoro-4-(4-ethoxy-pyrimidin-2-yl)phenyl]pyrrolidin-3-yl}acetic acid,

2-{1-[2,6-difluoro-4-(4-isobutoxy-pyrimidin-2-yl)phenyl]pyrrolidin-3-yl}acetic acid,

2-{1-[2,6-difluoro-4-(6-isobutylamino-pyrazin-2-yl)phenyl]pyrrolidin-3-yl}acetic acid,

2-{1-[2,6-difluoro-4-(6-cyclopentylamino-pyrazin-2-yl)phenyl]pyrrolidin-3-yl}acetic acid,

2-{1-[2,6-difluoro-4-(6-isopropylamino-pyrazin-2-yl)phenyl]pyrrolidin-3-yl}acetic acid,

2-{1-[2,6-difluoro-4-(6-diethylamino-pyrazin-2-yl)phenyl]pyrrolidin-3-yl}acetic acid,

3-[6-(6-cyclobutoxy-pyrazin-2-yl)-thiochroman-2-yl]-propionic acid,

2-[1-[4-[4-(4-chlorophenoxy)pyrimidin-2-yl]-2,6-difluoro-phenyl]-4-piperidyl]acetic acid,

2-[1-[4-[4-(4-chlorophenoxy)pyrimidin-2-yl]-2,6-difluoro-phenyl]-pyrrolidin-3-yl]acetic acid,

2-[1-[4-[4-phenoxy-pyrimidin-2-yl]-2,6-difluoro-phenyl]-4-piperidyl]acetic acid,

2-[1-[4-[4-(4-fluorophenoxy)pyrimidin-2-yl]-2,6-difluoro-phenyl]-4-piperidyl]acetic acid,

2-[1-[4-[4-(4-pyridin-3-yloxy-pyrimidin-2-yl]-2,6-difluoro-phenyl]-4-piperidyl]acetic acid,

2-[1-[2,6-difluoro-4-[6-(4-fluorophenoxy)pyrazin-2-yl]phenyl]-4-piperidyl]acetic acid,

2-[1-[4-[4-(4-methoxyphenoxy)pyrimidin-2-yl]-2,6-difluoro-phenyl]-4-piperidyl]acetic acid,

2-[1-[2,6-difluoro-4-[4-(4-fluorophenoxy)-6-methyl-pyrimidin-2-yl]phenyl]-4-piperidyl]acetic acid,

2-[1-[4-[4-(p-tolyloxy)pyrimidin-2-yl]-2,6-difluoro-phenyl]-4-piperidyl]acetic acid,

2-[1-[4-[4-(3,4-difluorophenoxy)pyrimidin-2-yl]-2,6-difluoro-phenyl]-4-piperidyl]acetic acid,

2-[4-(4-cyclobutoxy-6-methyl-pyrimidin-2-yl)-2,6-difluoro-phenoxymethyl]-cyclopropane carboxylic acid,

2-[4-(4-cyclobutoxy-pyrimidin-2-yl)-2,6-difluoro-phenoxymethyl]-cyclopropane carboxylic acid,

2-[4-(4-cyclopropylmethoxy-pyrimidin-2-yl)-2,6-difluoro-phenoxymethyl]-cyclopropane carboxylic acid,

2-[4-(4-cyclopropylmethoxy-6-methyl-pyrimidin-2-yl)-2,6-difluoro-phenoxymethyl]-cyclopropane carboxylic acid,

2-[4-(6-cyclopropylmethoxy-pyrazin-2-yl)-2,6-difluoro-phenoxymethyl]-cyclopropane carboxylic acid,

2-[4-(6-cyclobutoxy-pyrazin-2-yl)-2,6-difluoro-phenoxymethyl]-cyclopropane carboxylic acid,

2-[2-chloro-4-(4-cyclobutoxy-6-methyl-pyrimidin-2-yl)-6-fluoro-phenoxymethyl]-cyclopropane carboxylic acid,

{1-[4-(4-cyclobutoxy-6-methyl-pyrimidin-2-yl)-2,6-difluoro-phenyl]-pyrrolidin-3-yl}-acetic acid,

{1-[4-(4-cyclopropylmethoxy-6-methyl-pyrimidin-2-yl)-2,6-difluoro-phenyl]-pyrrolidin-3-yl}-acetic acid,

{1-[4-(6-cyclobutoxy-pyrazin-2-yl)-2,6-difluoro-phenyl]-pyrrolidin-3-yll}-acetic acid,

{1-[4-(4-cyclobutoxy-pyrimidin-2-yl)-2,6-difluoro-phenyl]-pyrrolidin-3-yl}-acetic acid,

{1-[4-(6-cyclopropylmethoxy-pyrazin-2-yl)-2,6-difluoro-phenyl]-pyrrolidin-3-yl}-acetic acid,

{1-[4-(4-cyclopropylmethoxy-pyrimidin-2-yl)-2,6-difluoro-phenyl]-pyrrolidin-3-yl}-acetic acid,

{1-[2,6-difluoro-4-(6-methoxy-pyrazin-2-yl)-phenyl]-pyrrolidin-3-yl}-acetic acid,

{1-[4-(6-ethoxy-pyrazin-2-yl)-2,6-difluoro-phenyl]-pyrrolidin-3-yl}-acetic acid,

{1-[2,6-difluoro-4-(6-isopropoxy-pyrazin-2-yl)-phenyl]-pyrrolidin-3-yl}-acetic acid,

{1-[2,6-difluoro-4-(4-isopropoxy-6-methyl-pyrimidin-2-yl)-phenyl]-pyrrolidin-3-yl}-acetic acid,

{1-[2,6-difluoro-4-(4-isobutoxy-6-methyl-pyrimidin-2-yl)-phenyl]-pyrrolidin-3-yl}-acetic acid,

{1-[2,6-difluoro-4-(4-methyl-6-propoxy-pyrimidin-2-yl)-phenyl]-pyrrolidin-3-yl}-acetic acid,

{1-[4-(4-ethoxy-6-methyl-pyrimidin-2-yl)-2,6-difluoro-phenyl]-pyrrolidin-3-yl}-acetic acid,

{1-[4-(4-cyclobutoxy-5-fluoro-pyrimidin-2-yl)-2,6-difluoro-phenyl]-pyrrolidin-3-yl}-acetic acid,

{1-[4-(4-cyclopropylmethoxy-5-fluoro-pyrimidin-2-yl)-2,6-difluoro-phenyl]-pyrrolidin-3-yl}-acetic acid,

{1-[2,6-difluoro-4-(5-fluoro-4-isobutoxy-pyrimidin-2-yl)-phenyl]-piperidin-4-yl}-acetic acid,

{1-[2,6-difluoro-4-(5-fluoro-4-propoxy-pyrimidin-2-yl)-phenyl]-piperidin-4-yl}-acetic acid,

(1-{2,6-difluoro-4-[4-(3-methyl-butoxy)-pyrimidin-2-yl]-phenyl}-piperidin-4-yl)-acetic acid,

(1-{2,6-difluoro-4-[4-(3-methoxy-propoxy)-pyrimidin-2-yl]-phenyl}-piperidin-4-yl)-acetic acid,

(1-{2,6-difluoro-4-[4-(3-methoxy-propoxy)-6-methyl-pyrimidin-2-yl]-phenyl}-piperidin-4-yl)-acetic acid,

(1-{2,6-difluoro-4-[4-(2-methoxy-ethoxy)-6-methyl-pyrimidin-2-yl]-phenyl}-piperidin-4-yl)-acetic acid,

2-[1-[2,6-difluoro-4-[4-[(6-methyl-3-pyridyl)oxy]pyrimidin-2-yl]phenyl]-4-piperidyl]acetic acid,

2-[1-[2,6-difluoro-4-[6-(4-ethylphenoxy)pyrimidin-2-yl]phenyl]-4-piperidyl]acetic acid,

2-[1-[4-[4-(3-fluorophenoxy)pyrimidin-2-yl]-2,6-difluoro-phenyl]-4-piperidyl]acetic acid,

2-[1-[2,6-difluoro-4-[4-(3,4-fluorophenoxy)-6-methyl-pyrimidin-2-yl]phenyl]-4-piperidyl]acetic acid,

2-[1-[2,6-difluoro-4-[4-(2-pyridyloxy)pyrimidin-2-yl]phenyl]-4-piperidyl]acetic acid,

2-[1-[2,6-difluoro-4-[4-[4-(trifluoromethyl)phenoxy]pyrimidin-2-yl]phenyl]-4-piperidyl]acetic acid,

2-[1-[2,6-difluoro-4-[4-[3-(trifluoromethyl)phenoxy]pyrimidin-2-yl]phenyl]-4-piperidyl]acetic acid,

2-[1-[2,6-difluoro-4-[4-methyl-6-[4-(trifluoromethyl)phenoxy]pyrimidin-2-yl]phenyl]-4-piperidyl]acetic acid,

2-[1-[2,6-difluoro-4-[4-methyl-6-[3-(trifluoromethyl)phenoxy]pyrimidin-2-yl]phenyl]-4-piperidyl]acetic acid,

{1-[4-(4-cyclobutoxy-6-trifluoromethyl-pyrimidin-2-yl)-2,6-difluoro-phenyl]-piperidin-4-yl}-acetic acid,

{1-[2,6-difluoro-4-(4-propoxy-6-trifluoromethyl-pyrimidin-2-yl)-phenyl]-piperidin-4-yl}-acetic acid, and

(1-{2,6-difluoro-4-[4-(4-fluoro-phenoxy)-6-trifluoromethyl-pyrimidin-2-yl]-phenyl}-piperidin-4-yl)-acetic acid,

or a pharmaceutically acceptable salt or stereoisomer thereof.

2. A pharmaceutical composition as a GPR120 agonist, comprising the compound, pharmaceutically acceptable salt or stereoisomer thereof as defined in claim 1 as an active ingredient and a pharmaceutically acceptable carrier.

Assignments (1)

ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Oct 4, 2017

From: KIM, YOUNG KWAN; PARK, SANG YUN; JOO, HYUN WOO; CHOI, EUN SIL; PAEK, SEUNG YUP; KANG, SEUNG WAN; KIM, BYUNG GYU; LEE, CHANG SEOK; KIM, SUNG WOOK; LEE, SANG DAE

To: LG CHEM, LTD.

Reel/Frame 043779/0777 →

Priority Claims (1)

KR 10-2014-0188399 · Dec 24, 2014 · national

Continuity (1)

Related Publication 20170349594A1 · Dec 7, 2017