US 10,221,138 B2Granted

Biaryl derivatives as GPR120 agonists

AssigneeLG Chem, Ltd.

InventorsYoung Kwan Kim, Sang Yun Park, Hyun Woo Joo, Eun Sil Choi

Life of this patent

Estimating the term…

Abstract

The present invention relates to biaryl derivatives of Formula 1, a method for preparing the same, a pharmaceutical composition comprising the same and use thereof. The biaryl derivatives of Formula 1 according to the present invention promote GLP-1 formation in the gastrointestinal tract and improve insulin resistance in the liver or in muscle due to anti-inflammatory action in macrophages, lipocytes, etc., and can accordingly be effectively used for preventing or treating diabetes, complications of diabetes, obesity, non-alcoholic fatty liver, steatohepatitis, osteoporosis or inflammation.

Claims10

Dependent claims

A biaryl derivative of Formula 1, or a pharmaceutically acceptable salt or isomer thereof:

wherein,
A and B represent independently phenyl or pyridine, provided that when B is phenyl, -G-COOR7 is substituted at the para position of phenyl, and when B is pyridine, -G-COOR7 is substituted at the 3 position of pyridine,
wherein R2-E may optionally not exist,
D and E represent independently carbon, nitrogen, oxygen or sulfur, or represent direct bond, or
R1 represents halogen;
C1-C6-alkyl optionally substituted by halogen, C3-C10-cycloalkyl, C1-C6-alkoxy, C1-C6-alkylamino, C3-C10-heterocycloalkyl or C1-C6-alkyl-C3-C10-heterocycloalkyl;
C3-C10-cycloalkyl optionally substituted by C3-C10-alkylsilanyloxy or hydroxy;
C2-C6-alkenyl;
C2-C6-alkynyl;
C3-C10-heterocycloalkyl optionally substituted by C1-C6-alkylamino or halogen;
C1-C6-alkyl-C3-C10-cycloalkyl;
C1-C6-alkyl-C3-C10-heterocycloalkyl;
aryl;
C1-C6-alkylaryl;
unsubstituted heteroaryl or C1-C6-alkyl-C5-C6-heteroaryl,
R2 represents hydrogen;
halogen;
C1-C6-alkyl optionally substituted by halogen, C3-C10-cycloalkyl, C1-C6-alkoxy, C1-C6-alkylamino, C3-C10-heterocycloalkyl or C1-C6-alkyl-C3-C10-heterocycloalkyl;
C3-C10-cycloalkyl optionally substituted by C3-C10-alkylsilanyloxy or hydroxy;
C2-C6-alkenyl;
C2-C6-alkynyl;
C3-C10-heterocycloalkyl optionally substituted by C1-C6-alkylamino or halogen;
C1-C6-alkyl-C3-C10-cycloalkyl;
C1-C6-alkyl-C3-C10-heterocycloalkyl;
aryl;
C1-C6-alkylaryl;
unsubstituted heteroaryl or C1-C6-alkyl-C5-C6-heteroaryl, and
when D and E represent nitrogen or carbon, R1 and R2 can represent two or three C1-C6-alkyl optionally substituted by C3-C10-cycloalkyl or C3-C10-heterocycloalkyl;
C3-C10-cycloalkyl;
C2-C6-alkenyl;
C2-C6-alkynyl;
C1-C6-alkyl-C3-C10-cycloalkyl;
aryl or C1-C6-alkylaryl which may be the same or different,
G represents -J-(CR5R6)p, wherein J represents oxygen or sulfur, R5 and R6 represent independently hydrogen, halogen, alkyl, cycloalkyl, hydroxyl or amine, and R5 and R6 which are substituted at the same or different carbon may be connected to form cycloalkyl,
R3 and R4 cannot independently exist depending on the number of m or n, or represent independently hydrogen, halogen, or optionally substituted C1-C6-alkyl or C1-C6-alkoxy,
R7 represents hydrogen, alkyl or cycloalkyl,
m and n represent independently an integer of 0 to 5,
p represents an integer of 2 to 6, and
wherein the isomer is at least one selected from the group consisting of an E-isomer, Z-isomer, R-isomer, S-isomer, racemic mixture and a diastereoisomer mixture.

36 more elements

A biaryl derivative, or a pharmaceutically acceptable salt or isomer thereof, which is selected from the following compounds:

4-[4-(6-phenoxy-2-pyridyl)phenoxy]butyric acid;
4-[2,6-difluoro-4-(6-isopropylsulfanyl-2-pyridyl)phenoxy]butyric acid;
4-[2,6-difluoro-4-(6-phenoxy-2-pyridyl)phenoxy]butyric acid;
4-[2-chloro-4-(6-isopropylsulfanyl-2-pyridyl)phenoxy]butyric acid;
4-[2-fluoro-4-(6-isopropylsulfanyl-2-pyridyl)phenoxy]butyric acid;
4-[4-(6-cyclopentylsulfanyl-2-pyridyl)-2,6-difluoro-phenoxy]butyric acid;
4-[4-(2-cyclobutylsulfanyl-pyridin-3-yl)-2-methoxy-phenoxy]-butyric acid;
4-[2,6-difluoro-4-(2-isopropylsulfanyl-4-pyridyl)phenoxy]butyric acid;
4-[4-[6-(cyclopentoxy)-2-pyridyl]-2,6-difluoro-phenoxy]butyric acid;
4-[4-(2-cyclobutylsulfanyl-pyridin-3-yl)-2,6-dimethyl-phenoxy]-butyric acid;
4-[4-[3-(cyclopentoxy)phenyl]-2,6-difluoro-phenoxy]butyric acid;
4-[2,6-difluoro-4-(6-pyrrolidin-1-yl-2-pyridyl)phenoxy]butyric acid;
4-[4-(2-sec-butylsulfanyl-pyridin-3-yl)-2,6-difluoro-phenoxy]-butyric acid;
4-[4-[3-(cyclopentoxy)phenyl]-2,3-difluoro-phenoxy]butyric acid;
4-[2,6-difluoro-4-[6-(1-piperidyl)-2-pyridyl]phenoxy]butyric acid;
4-[4-(6-anilino-2-pyridyl)-2,6-difluoro-phenoxy]butyric acid;
4-[2,6-difluoro-4-[6-(N-methylanilino)-2-pyridyl]phenoxy]butyric acid;
4-[4-[6-(cyclopentylamino)-2-pyridyl]-2,6-difluoro-phenoxy]butyric acid;
4-[4-[6-(cyclopropylmethylsulfanyl)-2-pyridyl]-2,6-difluoro-phenoxy]butyric acid;
4-[4-(6-cyclobutylsulfanyl-2-pyridyl)-2,6-difluoro-phenoxy]butyric acid;
4-[2,6-difluoro-4-(6-propylsulfanyl-2-pyridyl)phenoxy]butyric acid;
4-[2,6-difluoro-4-(6-isopropoxy-2-pyridyl)phenoxy]butyric acid;
4-[2,6-difluoro-4-(6-propoxy-2-pyridyl)phenoxy]butyric acid;
4-[4-[6-(cyclopropylmethoxy)-2-pyridyl]-2,6-difluoro-phenoxy]butyric acid;
4-[4-[6-(cyclobutoxy)-2-pyridyl]-2,6-difluoro-phenoxy]butyric acid;
4-[4-[6-(cyclobutoxy)-2-pyridyl]-2-methyl-phenoxy]butyric acid;
4-[4-[6-(cyclobutoxy)-2-pyridyl]-2-(trifluoromethyl)phenoxy]butyric acid;
4-[4-(2-cyclobutylsulfanyl-3-pyridyl)-2,6-difluoro-phenoxy]pentanoic acid;
4-[4-[6-(cyclobutoxy)-2-pyridyl]-2,6-difluoro-phenoxy]pentanoic acid;
4-[[5-(2-cyclobutylsulfanyl-3-pyridyl)-2-pyridyl]oxy]pentanoic acid;
4-{2,6-difluoro-4-[2-(3-methyl-butylsulfanyl)-pyridin-3-yl]-phenoxy}-butyric acid
4-{2,6-difluoro-4-[2-(2-fluoro-ethoxy)-pyridin-3-yl]-phenoxy}-butyric acid;
2-[1-[[4-(2-cyclobutylsulfanyl-3-pyridyl)-2,6-difluoro-phenoxy]methyl]cyclopropyl]acetic acid;
2-[1-[[4-[3-(cyclobutoxy)phenyl]-2,6-difluoro-phenoxy]methyl]cyclopropyl]acetic acid;
4-[[6-[3-(cyclobutoxy)phenyl]-3-pyridyl]oxy]butyric acid;
4-[[6-[3-(cyclopentoxy)phenyl]-3-pyridyl]oxy]butyric acid;
4-(2′-phenoxy-biphenyl-4-yloxy)-butyric acid;
4-[4-(2-isopropylsulfanyl-pyridin-3-yl)-phenoxy]-butyric acid;
4-(3,5-difluoro-2′-phenoxy-biphenyl-4-yloxy)-butyric acid;
4-[4-(2-cyclopentylsulfanyl-pyridin-3-yl)-phenoxy]-butyric acid;
4-[2,6-difluoro-4-(2-isopropylsulfanyl-pyridin-3-yl)-phenoxy]-butyric acid;
4-[2,6-difluoro-4-(2-phenoxy-pyridin-3-yl)-phenoxy]-butyric acid;
4-[2,6-difluoro-4-(2-isopropoxy-pyridin-3-yl)-phenoxy]-butyric acid;
4-[4-(2-cyclopentyloxy-pyridin-3-yl)-2,6-difluoro-phenoxy]-butyric acid;
4-[4-(2-cyclopentylsulfanyl-pyridin-3-yl)-2,6-difluoro-phenoxy]-butyric acid;
4-[4-(2-cyclopropylmethoxy-pyridin-3-yl)-2,6-difluoro-phenoxy]-butyric acid;
4-[4-(2-cyclopropylmethylsulfanyl-pyridin-3-yl)-2,6-difluoro-phenoxy]-butyric acid;
4-[4-(2-cyclobutylsulfanyl-pyridin-3-yl)-phenoxy]-butyric acid;
4-[4-(2-cyclopropylmethylsulfanyl-pyridin-3-yl)-phenoxy]-butyric acid;
4-[4-(2-cyclobutylsulfanyl-pyridin-3-yl)-2,6-difluoro-phenoxy]-butyric acid;
4-[4-(2-propylsulfanyl-pyridin-3-yl)-phenoxy]-butyric acid;
4-(3,5-difluoro-2′-isopropoxy-biphenyl-4-yloxy)-butyric acid;
4-(2′-cyclobutoxy-3,5-difluoro-biphenyl-4-yloxy)-butyric acid;
4-(2′-cyclopropylmethoxy-3,5-difluoro-biphenyl-4-yloxy)-butyric acid;
4-(2′-cyclopentyloxy-3,5-difluoro-biphenyl-4-yloxy)-butyric acid;
4-(2′-cyclopentyloxy-biphenyl-4-yloxy)-butyric acid;
4-(2′-isopropoxy-biphenyl-4-yloxy)-butyric acid;
4-(2′-cyclopropylmethoxy-biphenyl-4-yloxy)-butyric acid;
4-[4-(2-cyclobutylsulfanyl-pyridin-3-yl)-2,6-difluoro-phenoxy]-2-methyl-butyric acid;
2-[4-(2-cyclobutylsulfanyl-pyridin-3-yl)-2,6-difluoro-phenoxymethyl]-cyclopropanecarboxylic acid;
4-[4-(2-cyclobutylsulfanyl-pyridin-3-yl)-2,5-difluoro-phenoxy]-butyric acid;
4-[4-(6-cyclobutylsulfanyl-pyridin-2-yl)-2,5-difluoro-phenoxy]-butyric acid;
4-[4-(2-tert-butylsulfanyl-pyridin-3-yl)-2,6-difluoro-phenoxy]-butyric acid;
6-[2,6-difluoro-4-(2-propylsulfanyl-3-pyridyl)phenoxy]hexanoic acid;
4-{2,6-difluoro-4-[6-(2-methyl-propenyl)-pyridin-2-yl]-phenoxy}-butyric acid;
4-[2,6-difluoro-4-(6-isobutyl-pyridin-2-yl)-phenoxy]-butyric acid;
4-[4-(2-cyclobutylsulfanyl-pyridin-3-yl)-3,5-difluoro-phenoxy]-butyric acid;
4-{2,6-difluoro-4-[2-(tetrahydro-pyran-4-yloxy)-pyridin-3-yl]-phenoxy}-butyric acid;
4-{2,6-difluoro-4-[2-(tetrahydro-furan-3-yloxy)-pyridin-3-yl]-phenoxy}-butyric acid;
4-[4-(2-cyclobutoxy-pyridin-3-yl)-2,6-difluoro-phenoxy]-butyric acid;
4-{2,6-difluoro-4-[2-(2-methoxy-ethoxy)-pyridin-3-yl]-phenoxy}-butyric acid;
4-[2,6-difluoro-4-(2-pyrrolidin-1-yl-3-pyridyl)phenoxy]butanoic acid;
4-[4-[2-(cyclopentylamino)-3-pyridyl]-2,6-difluoro-phenoxy]butanoic acid;
4-[4-[2-(cyclopropylmethylamino)-3-pyridyl]-2,6-difluoro-phenoxy]butanoic acid;
4-[4-[6-(cyclopropylmethylamino)-2-pyridyl]-2,6-difluoro-phenoxy]butanoic acid;
4-[2,6-difluoro-4-[2-(isopropylamino)-3-pyridyl]phenoxy]butanoic acid;
4-[4-[2-(cyclopropylamino)-3-pyridyl]-2,6-difluoro-phenoxy]butanoic acid;
4-[2,6-difluoro-4-[6-(isopropylamino)-2-pyridyl]phenoxy]butanoic acid;
4-[4-[2-(cyclopentylamino)phenyl]-2,6-difluoro-phenoxy]butanoic acid;
4-[4-[3-(cyclopentylamino)phenyl]-2,6-difluoro-phenoxy]butanoic acid;
4-[2,6-difluoro-4-[2-(propylamino)phenyl]phenoxy]butanoic acid;
4-[4-[2-(cyclopropylmethylamino)phenyl]-2,6-difluoro-phenoxy]butanoic acid;
4-[2,6-difluoro-4-[2-(isopropylamino)phenyl]phenoxy]butanoic acid;
4-[4-[2-(cyclopentylamino)phenyl]phenoxy]butanoic acid;
4-[4-[2-(cyclopropylmethylamino)phenyl]phenoxy]butanoic acid;
4-[4-[2-(propylamino)phenyl]phenoxy]butanoic acid;
4-[4-[2-(isopropylamino)phenyl]phenoxy]butanoic acid;
4-[4-[2-(cyclobutylamino)phenyl]phenoxy]butanoic acid;
4-[4-[2-(cyclobutylamino)phenyl]-2,6-difluoro-phenoxy]butanoic acid;
4-[4-[3-(cyclopropylmethylamino)phenyl]-2,6-difluoro-phenoxy]butanoic acid;
4-[2,6-difluoro-4-[3-(isopropylamino)phenyl]phenoxy]butanoic acid;
4-[2,6-difluoro-4-(3-pyrrolidin-1-ylphenyl)phenoxy]butanoic acid;
4-[4-[3-(cyclobutylamino)phenyl]-2,6-difluoro-phenoxy]butanoic acid;
4-[2,6-difluoro-4-[3-(propylamino)phenyl]phenoxy]butanoic acid;
4-[4-[5-chloro-2-(cyclopentylamino)phenyl]-2,6-difluoro-phenoxy]butanoic acid;
4-[4-[2-(cyclopentylamino)-5-fluoro-phenyl]-2,6-difluoro-phenoxy]butanoic acid;
4-[4-(3-cyclopentylphenyl)-2,6-difluoro-phenoxy]butanoic acid;
4-[4-[3-(cyclopentylmethyl)phenyl]-2,6-difluoro-phenoxy]butanoic acid;
4-[4-[2-(cyclopentylmethyl)phenyl]-2,6-difluoro-phenoxy]butanoic acid;
4-[4-[6-(cyclopentylmethyl)-2-pyridyl]-2,6-difluoro-phenoxy]butanoic acid;
4-[4-[2-(cyclobutylmethyl)phenyl]-2,6-difluoro-phenoxy]butanoic acid;
4-[4-[3-(cyclobutylmethyl)phenyl]-2,6-difluoro-phenoxy]butanoic acid;
4-[4-[6-(cyclobutylmethyl)-2-pyridyl]-2,6-difluoro-phenoxy]butanoic acid;
4-[4-(2-cyclopentylphenyl)-2,6-difluoro-phenoxy]butanoic acid;
4-[4-(6-cyclopentyl-2-pyridyl)-2,6-difluoro-phenoxy]butanoic acid;
4-[2,6-difluoro-4-(2-isobutyl-3-pyridyl)phenoxy]butanoic acid;
4-[4-(2-cyclopentyl-3-pyridyl)-2,6-difluoro-phenoxy]butanoic acid;
4-[4-[2-(cyclopentylmethyl)-3-pyridyl]-2,6-difluoro-phenoxy]butanoic acid;
4-[2,6-difluoro-4-(2-pyrrol-1-yl-3-pyridyl)phenoxy]butanoic acid;
4-[2,6-difluoro-4-[2-(4-methylpyrazol-1-yl)-3-pyridyl]phenoxy]butanoic acid;
4-[2,6-difluoro-4-(2-morpholino-3-pyridyl)phenoxy]butanoic acid;
4-[2,6-difluoro-4-[2-(tetrahydropyran-4-ylmethylamino)-3-pyridyl]phenoxy]butanoic acid;
4-[2,6-difluoro-4-[2-(1-piperidyl)-3-pyridyl]phenoxy]butanoic acid;
(4S)-4-[4-(2-cyclobutylsulfanyl-3-pyridyl)-2,6-difluoro-phenoxy]pentanoic acid;
(4R)-4-[4-(2-cyclobutylsulfanyl-3-pyridyl)-2,6-difluoro-phenoxy]pentanoic acid;
(4R)-4-[4-[3-(cyclobutoxy)phenyl]-2,6-difluoro-phenoxy]pentanoic acid;
(4R)-4-[4-(2-cyclopentylsulfanyl-3-pyridyl)-2,6-difluoro-phenoxy]pentanoic acid;
(4R)-4-[2,6-difluoro-4-(3-phenoxyphenyl)phenoxy]pentanoic acid;
4-(3′-cyclobutoxy-biphenyl-4-ylsulfanyl)-butyric acid;
4-(3′-isopropoxy-biphenyl-4-ylsulfanyl)-butyric acid;
[1-(3,5-difluoro-3′-isopropoxy-biphenyl-4-ylsulfanylmethyl)-cyclopropyl]-acetic acid;
4-(3′-cyclopentyloxy-3,5-difluoro-biphenyl-4-ylsulfanyl)-butyric acid;
4-[4-(2-cyclopentyloxy-pyridin-3-yl)-phenylsulfanyl]-butyric acid;
4-[4-(2-cyclopropylmethoxy-pyridin-3-yl)-phenylsulfanyl]-butyric acid;
4-(3′-phenoxy-biphenyl-4-ylsulfanyl)-butyric acid;
4-(3′-cyclopentyloxy-biphenyl-4-ylsulfanyl)-butyric acid;
4-(3′-propoxy-biphenyl-4-ylsulfanyl)-butyric acid;
4-[4-(6-cyclobutoxy-pyridin-2-yl)-phenylsulfanyl]-butyric acid;
4-[4-(6-cyclopentyloxy-pyridin-2-yl)-phenylsulfanyl]-butyric acid;
4-[4-(6-isopropoxy-pyridin-2-yl)-phenylsulfanyl]-butyric acid;
4-[4-(2-isopropoxy-pyridin-3-yl)-phenylsulfanyl]-butyric acid;
4-[4-(6-propoxy-pyridin-2-yl)-phenylsulfanyl]-butyric acid;
4-[4-(6-cyclopentylsulfanyl-pyridin-2-yl)-phenylsulfanyl]-butyric acid;
4-(3′-cyclobutoxy-3,5-difluoro-biphenyl-4-ylsulfanyl)-butyric acid;
4-(3,5-difluoro-3′-isopropoxy-biphenyl-4-ylsulfanyl)-butyric acid;
4-[2,6-difluoro-4-(6-propoxy-pyridin-2-yl)-phenylsulfanyl]-butyric acid;
4-[2,6-difluoro-4-(6-isopropoxy-pyridin-2-yl)-phenylsulfanyl]-butyric acid;
4-[2,6-difluoro-4-(2-isopropoxy-pyridin-3-yl)-phenylsulfanyl]-butyric acid;
4-[2,6-difluoro-4-(2-propoxy-pyridin-3-yl)-phenylsulfanyl]-butyric acid;
4-[2,6-difluoro-4-(6-isopropylsulfanyl-pyridin-2-yl)-phenylsulfanyl]-butyric acid;
4-[2,6-difluoro-4-(6-propylsulfanyl-pyridin-2-yl)-phenylsulfanyl]-butyric acid;
4-[4-(2-cyclobutylsulfanyl-pyridin-3-yl)-2,6-difluoro-phenylsulfanyl]-butyric acid;
4-[4-(2-cyclobutoxy-pyridin-3-yl)-phenylsulfanyl]-butyric acid;
4-[4-(2-cyclobutoxy-pyridin-3-yl)-2,6-difluoro-phenylsulfanyl]-butyric acid;
4-[4-(2-cyclopentyloxy-pyridin-3-yl)-2,6-difluoro-phenylsulfanyl]-butyric acid;
4-[2,6-difluoro-4-(2-isopropylsulfanyl-pyridin-3-yl)-phenylsulfanyl]-butyric acid;
4-[4-(2-cyclopentylsulfanyl-pyridin-3-yl)-2,6-difluoro-phenylsulfanyl]-butyric acid;
4-[4-(2-isopropylsulfanyl-pyridin-3-yl)-phenylsulfanyl]-butyric acid;
4-[4-(2-cyclopentylsulfanyl-pyridin-3-yl)-phenylsulfanyl]-butyric acid;
4-[2-fluoro-4-(6-isopropoxy-pyridin-2-yl)-phenylsulfanyl]-butyric acid;
4-[4-(2-cyclopentyloxy-pyridin-3-yl)-2-fluoro-phenylsulfanyl]-butyric acid;
4-[4-(2-cyclobutylsulfanyl-pyridin-3-yl)-2-fluoro-phenylsulfanyl]-butyric acid;
4-[4-(2-cyclobutylsulfanyl-pyridin-3-yl)-phenylsulfanyl]-butyric acid;
4-[4-(6-cyclobutoxy-pyridin-2-yl)-2,6-difluoro-phenylsulfanyl]-butyric acid;
4-[4-(6-cyclopentyloxy-pyridin-2-yl)-2,6-difluoro-phenylsulfanyl]-butyric acid;
4-[4-(6-cyclobutylsulfanyl-pyridin-2-yl)-phenylsulfanyl]-butyric acid;
4-[4-(6-cyclopropylmethoxy-pyridin-2-yl)-2,6-difluoro-phenylsulfanyl]-butyric acid;
4-[4-(6-cyclobutylsulfanyl-pyridin-2-yl)-2,6-difluoro-phenylsulfanyl]-butyric acid;
4-[4-(6-cyclopentylsulfanyl-pyridin-2-yl)-2,6-difluoro-phenylsulfanyl]-butyric acid;
4-(2′-cyclopentylamino-3-fluoro-biphenyl-4-ylsulfanyl)-butyric acid;
4-(2′-cyclopentylamino-3,5-difluoro-biphenyl-4-ylsulfanyl)-butyric acid;
4-[2′-(cyclopropylmethyl-amino)-3,5-difluoro-biphenyl-4-ylsulfanyl]-butyric acid;
4-[2-fluoro-4-(2-isopropylsulfanyl-pyridin-3-yl)-phenylsulfanyl]-butyric acid;
4-[4-(2-cyclopentylsulfanyl-pyridin-3-yl)-2-fluoro-phenylsulfanyl]-butyric acid;
4-(3,5-difluoro-2′-isopropylamino-biphenyl-4-ylsulfanyl)-butyric acid;
4-(3,5-difluoro-2′-propylamino-biphenyl-4-ylsulfanyl)-butyric acid;
4-[4-(2-cyclopropylmethoxy-pyridin-3-yl)-2,6-difluoro-phenylsulfanyl]-butyric acid;
4-[2,6-difluoro-4-(2-propylsulfanyl-pyridin-3-yl)-phenylsulfanyl]-butyric acid;
4-[4-(6-cyclobutylsulfanyl-pyridin-2-yl)-2-fluoro-phenylsulfanyl]-butyric acid;
4-[4-(2-cyclopentylamino-pyridin-3-yl)-2-fluoro-phenylsulfanyl]-butyric acid;
4-[2-fluoro-4-(2-isopropoxy-pyridin-3-yl)-phenylsulfanyl]-butyric acid;
4-[4-(2-cyclobutoxy-pyridin-3-yl)-2-fluoro-phenylsulfanyl]-butyric acid;
4-[2-fluoro-4-(2-pyrrolidin-1-yl-pyridin-3-yl)-phenylsulfanyl]-butyric acid;
4-[2-fluoro-4-(2-isopropylamino-pyridin-3-yl)-phenylsulfanyl]-butyric acid;
4-(2′-cyclopentylamino-3,5′-difluoro-biphenyl-4-ylsulfanyl)-butyric acid;
4-(2′-cyclopentylamino-5′-fluoro-biphenyl-4-ylsulfanyl)-butyric acid;
4-(2′-cyclopentyloxy-5′-methyl-biphenyl-4-ylsulfanyl)-butyric acid;
4-(2′-cyclopentyloxy-4′-methoxy-biphenyl-4-ylsulfanyl)-butyric acid;
4-(2′-cyclopentyloxy-5′-fluoro-biphenyl-4-ylsulfanyl)-butyric acid;
4-(2′-cyclopentyloxy-3,5′-difluoro-biphenyl-4-ylsulfanyl)-butyric acid;
4-[4-(2-cyclopentyloxy-5-methyl-pyridin-3-yl)-phenylsulfanyl]-butyric acid;
4-(2′-cyclopentyloxy-3,5,5′-trifluoro-biphenyl-4-ylsulfanyl)-butyric acid;
4-(2′-cyclopentyloxy-3-fluoro-4′-methoxy-biphenyl-4-ylsulfanyl)-butyric acid;
4-(2′-cyclopentyloxy-3,5-difluoro-4′-methoxy-biphenyl-4-ylsulfanyl)-butyric acid;
4-(3-fluoro-2′-isopropoxy-4′-methoxy-biphenyl-4-ylsulfanyl)-butyric acid;
4-[4-(2-cyclopentyloxy-5-methyl-pyridin-3-yl)-2-fluoro-phenylsulfanyl]-butyric acid;
4-[2-fluoro-4-(2-isopropoxy-5-methyl-pyridin-3-yl)-phenylsulfanyl]-butyric acid;
4-(3,5′-difluoro-2′-isopropoxy-biphenyl-4-ylsulfanyl)-butyric acid;
4-[4-(2-cyclopentyloxy-6-methyl-pyridin-3-yl)-2-fluoro-phenylsulfanyl]-butyric acid;
4-(3,3′-difluoro-2′-isopropoxy-5′-methyl-biphenyl-4-ylsulfanyl)-butyric acid;
4-(3,3′-difluoro-5′-methyl-2′-propoxy-biphenyl-4-ylsulfanyl)-butyric acid;
4-(3-fluoro-2′,4′-dipropoxy-biphenyl-4-ylsulfanyl)-butyric acid;
4-(6′-cyclopentyloxy-3,2′-difluoro-3′-methyl-biphenyl-4-ylsulfanyl)-butyric acid;
4-(2′-cyclopentyloxy-3,3′-difluoro-biphenyl-4-ylsulfanyl)-butyric acid;
4-(2′-cyclopentyloxy-3,3′-difluoro-5′-methyl-biphenyl-4-ylsulfanyl)-butyric acid;
5-[4-(2-cyclobutylmethoxy-pyridin-3-yl)-2,6-difluoro-phenoxy]-pentanoic acid;
5-[4-(2-cyclopropoxy-pyridin-3-yl)-2,6-difluoro-phenoxy]-pentanoic acid;
4-[4-(2-cyclopentyloxy-5-methyl-pyridin-3-yl)-2,6-difluoro-phenylsulfanyl]-butyric acid;
4-[4-(2-cyclopentyloxy-pyridin-3-yl)-phenylsulfanyl]-pentanoic acid;
4-[4-(2-isopropoxy-pyridin-3-yl)-phenylsulfanyl]-pentanoic acid;
4-[4-(2-cyclopentyloxy-pyridin-3-yl)-2,6-difluoro-phenylsulfanyl]-pentanoic acid;
4-[4-(2-cyclopentylsulfanyl-pyridin-3-yl)-2,6-difluoro-phenylsulfanyl]-pentanoic acid;
4-[4-[2-(2-dimethylaminoethyloxy)-3-pyridyl]-2,6-difluoro-phenoxy]butanoic acid;
4-[2,6-difluoro-4-(2-propylsulfanyl-pyridin-3-yl)-phenoxy]-butanoic acid;
4-[4-(2-cyclopropylsulfanyl-pyridin-3-yl)-2,6-difluoro-phenoxy]-butanoic acid;
4-[4-(2-ethylsulfanyl-pyridin-3-yl)-2,6-difluoro-phenoxy]-butanoic acid;
4-[4-(2-butylsulfanyl-pyridin-3-yl)-2,6-difluoro-phenoxy]-butanoic acid;
4-(2′-cyclopentylamino-biphenyl-4-ylsulfanyl)-butyric acid;
4-[4-(2-cyclopentyloxy-5-methyl-pyridin-3-yl)-2,6-difluoro-phenoxy]-butyric acid;
4-[4-(6-isopropylsulfanyl-2-pyridyl)phenoxy]butanoic acid;
4-[2,6-difluoro-4-(3-phenoxyphenyl)phenoxy]butanoic acid;
4-[4-[6-[3-(dimethylamino)pyrrolidin-1-yl]-2-pyridyl]-2,6-difluoro-phenoxy]butanoic acid;
5-[2,6-difluoro-4-(2-isopropoxy-pyridin-3-yl)-phenoxy]-pentanoic acid
5-[4-(2-cyclobutoxy-pyridin-3-yl)-2,6-difluoro-phenoxy]-pentanoic acid
4-[4-[2-(3,3-difluoropyrrolidin-1-yl)-3-pyridyl]-2,6-difluoro-phenoxy]butanoic acid;
4-[2,6-difluoro-4-[2-(4-methylpiperazin-1-yl)-3-pyridyl]phenoxy]butanoic acid;
4-[2,6-difluoro-4-[2-(5-methylisoxazol-3-yl)oxy-3-pyridyl]phenoxy]butanoic acid;
4-[4-[2-[2-(aziridin-1-yl)ethoxy]-3-pyridyl]-2,6-difluoro-phenoxy]butanoic acid;
4-[2,6-difluoro-4-[2-(3-furylmethoxy)-3-pyridyl]phenoxy]butanoic acid;
4-[2,6-difluoro-4-[2-(2-furylmethoxy)-3-pyridyl]phenoxy]butanoic acid;
4-[2,6-difluoro-4-[2-[(3-methyloxetan-3-yl)methoxy]-3-pyridyl]phenoxy]butanoic acid;
4-[2,6-difluoro-4-[2-(tetrahydrofuran-3-ylmethoxy)-3-pyridyl]phenoxy]butanoic acid;
4-[2,6-difluoro-4-[2-(tetrahydrofuran-2-ylmethoxy)-3-pyridyl]phenoxy]butanoic acid;
4-[4-(2-cyclobutylmethoxy-pyridin-3-yl)-2,6-difluoro-phenoxy]-butyric acid;
4-[4-(2-cyclopropoxy-pyridin-3-yl)-2,6-difluoro-phenoxy]-butyric acid;
4-(4-{2-[3-(tert-butyl-dimethyl-silanyloxy)-cyclopentyloxy]-pyridin-3-yl}-2,6-difluoro-phenoxy)-butyric acid;
4-{2,6-difluoro-4-[2-(3-hydroxy-cyclopentyloxy)-pyridin-3-yl]-phenoxy}-butyric acid;
4-[4-(2-cyclohexyloxy-pyridin-3-yl)-2,6-difluoro-phenoxy]-butyric acid;
4-[4-(2-cyclopentylmethoxy-pyridin-3-yl)-2,6-difluoro-phenoxy]-butyric acid;
4-[2,6-difluoro-4-(2-isobutoxy-pyridin-3-yl)-phenoxy]-butyric acid;
4-{4-[2-(2,2-dimethy-propoxy)-pyridin-3-yl]-2,6-difluoro-phenoxy}-butyric acid;
5-[4-(2-cyclopentyloxy-pyridin-3-yl)-2,6-difluoro-phenoxy]-pentanoic acid;
5-[4-(2-cyclobutylsulfanyl-3-pyridyl)-2,6-difluoro-phenoxy]pentanoic acid;
5-[4-(2-cyclopentylsulfanyl-3-pyridyl)-2,6-difluoro-phenoxy]pentanoic acid;
5-[2,6-difluoro-4-(2-isopropylsulfanyl-3-pyridyl)phenoxy]pentanoic acid;
5-[2,6-difluoro-4-(2-propylsulfanyl-3-pyridyl)phenoxy]pentanoic acid;
5-[2,6-difluoro-4-(6-isopropylsulfanyl-2-pyridyl)phenoxy]pentanoic acid;
5-[2,6-difluoro-4-(6-isopropoxy-2-pyridyl)phenoxy]pentanoic acid;
5-[4-[2-(cyclopropylmethoxy)-3-pyridyl]-2,6-difluoro-phenoxy]pentanoic acid;
5-[2,6-difluoro-4-(2-tetrahydrofuran-3-yloxy-3-pyridyl)phenoxy]pentanoic acid;
5-[2,6-difluoro-4-(2-tetrahydropyran-4-yloxy-3-pyridyl)phenoxy]pentanoic acid;
4-[2,6-difluoro-4-(2-isopropoxy-pyridin-3-yl)-phenylsulfanyl]-pentanoic acid;
4-[4-(2-cyclopentylsulfanyl-pyridin-3-yl)-phenylsulfanyl]-pentanoic acid;
4-{2-fluoro-4-[2-(tetrahydro-pyran-4-yloxy)-pyridin-3-yl]-phenylsulfanyl}-butyric acid;
4-{2-fluoro-4-[2-(tetrahydrofuran-3-yloxy)-pyridin-3-yl]-phenylsulfanyl}-butyric acid;
4-[4-(2-cyclobutylmethoxy-pyridin-3-yl)-2-fluoro-phenylsulfanyl]-butyric acid;
4-{2,6-difluoro-4-[2-(2,2,2-trifluoro-ethoxy)-pyridin-3-yl]-phenylsulfanyl}-butyric acid;
4-[4-(2-cyclobutylmethoxy-pyridin-3-yl)-2,6-difluoro-phenylsulfanyl]-butyric acid;
4-[4-(2-cyclopentylamino-pyridin-3-yl)-2,6-difluoro-phenylsulfanyl]-butyric acid;
4-[2,6-difluoro-4-(2-isopropylamino-pyridin-3-yl)-phenylsulfanyl]-butyric acid;
4-{4-[2-(cyclopropylmethyl-amino)-pyridin-3-yl]-2,6-difluoro-phenylsulfanyl}-butyric acid;
5-[4-(2-cyclopentyloxy-pyridin-3-yl)-2,6-difluoro-phenylsulfanyl]-pentanoic acid;
5-[2,6-difluoro-4-(2-isopropoxy-pyridin-3-yl)-phenylsulfanyl]-pentanoic acid;
5-[4-(2-cyclopentyloxy-pyridin-3-yl)-phenylsulfanyl]-pentanoic acid;
5-[4-(2-isopropoxy-pyridin-3-yl)-phenylsulfanyl]-pentanoic acid;
5-[4-(2-cyclopentylsulfanyl-pyridin-3-yl)-2,6-difluoro-phenylsulfanyl]-pentanoic acid;
5-[2,6-difluoro-4-(2-propylsulfanyl-pyridin-3-yl)-phenylsulfanyl]-pentanoic acid;
5-[4-(2-cyclopentylsulfanyl-pyridin-3-yl)-phenylsulfanyl]-pentanoic acid;
5-[4-(2-cyclobutylsulfanyl-pyridin-3-yl)-phenylsulfanyl]-pentanoic acid;
5-[4-(2-cyclobutylmethoxy-pyridin-3-yl)-2,6-difluoro-phenylsulfanyl]-pentanoic acid;
5-[4-(2-cyclobutoxy-pyridin-3-yl)-2,6-difluoro-phenylsulfanyl]-pentanoic acid;
6-[4-(2-cyclopentyloxy-pyridin-3-yl)-2,6-difluoro-phenoxy]-hexanoic acid;
7-[4-(2-cyclopentyloxy-pyridin-3-yl)-2,6-difluoro-phenoxy]-heptanoic acid;
5-[2-fluoro-4-(2-isopropoxy-pyridin-3-yl)-phenoxy]-pentanoic acid;
5-[4-(2-cyclopentylsulfanyl-pyridin-3-yl)-2-fluoro-phenoxy]-pentanoic acid;
5-[4-(2-cyclobutylsulfanyl-pyridin-3-yl)-2-fluoro-phenoxy]-pentanoic acid;
5-[4-(2-cyclopentyloxy-pyridin-3-yl)-2-fluoro-phenoxy]-pentanoic acid;
4-[2,6-difluoro-4-(2-methoxy-pyridin-3-yl)-phenoxy]-butyric acid;
4-[4-(2-allyloxy-pyridin-3-yl)-2,6-difluoro-phenoxy]-butyric acid;
4-[4-(2-but-2-ynyloxy-pyridin-3-yl)-2,6-difluoro-phenoxy]-butyric acid;
6-[4-[2-(cyclobutoxy)-3-pyridyl]-2,6-difluoro-phenoxy]hexanoic acid;
6-[4-[2-(cyclobutylmethoxy)-3-pyridyl]-2,6-difluoro-phenoxy]hexanoic acid;
6-[4-[2-(cyclopropylmethoxy)-3-pyridyl]-2,6-difluoro-phenoxy]hexanoic acid;
6-[4-(2-cyclobutylsulfanyl-3-pyridyl)-2,6-difluoro-phenoxy]hexanoic acid;
6-[4-(2-cyclopentylsulfanyl-3-pyridyl)-2,6-difluoro-phenoxy]hexanoic acid;
6-[4-(2-cyclopentyloxy-pyridin-3-yl)-2,6-difluoro-phenylsulfanyl]-hexanoic acid;
6-[4-(2-cyclopentylsulfanyl-pyridin-3-yl)-2,6-difluoro-phenylsulfanyl]-hexanoic acid;
6-[4-(2-cyclobutylsulfanyl-pyridin-3-yl)-2,6-difluoro-phenylsulfanyl]-hexanoic acid;
and
6-[2,6-difluoro-4-(2-propylsulfanyl-pyridin-3-yl)-phenylsulfanyl]-hexanoic acid, and
wherein the isomer is at least one selected from the group consisting of an E-isomer, Z-isomer, R-isomer, S-isomer, racemic mixture and a diastereoisomer mixture.

278 more elements

Dependencies are inferred from the claim text.

Facts

Application: 14/894,928Filed 26 Jun 2014
Priority: KR 10-2013-007492727 Jun 2013
Published: US 2016/0168096 A116 Jun 2016
Granted: 5 Mar 2019
Term ends: Not estimatedThe source records don’t support an estimate.

Classification28 codes

C07D 213/643
Attached in position 2 or 6: 2-Phenoxypyridines; Derivatives thereof
A61P 1/16
Drugs for disorders of the alimentary tract or the digestive system: for liver or gallbladder disorders, e.g. hepatoprotective agents,…
A61P 3/00
Drugs for disorders of the metabolism
A61P 3/04
Drugs for disorders of the metabolism: anorexiants; Antiobesity agents

Family

US 2016/0168096 A1Pre-grant publication · published 16 Jun 2016
US 10,221,138 B2This patent

From the US filing history. Foreign family members aren’t listed.

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Abstract

A biaryl derivative of Formula 1, or a pharmaceutically acceptable salt or isomer thereof:

wherein,
A and B represent independently phenyl or pyridine, provided that when B is phenyl, -G-COOR7 is substituted at the para position of phenyl, and when B is pyridine, -G-COOR7 is substituted at the 3 position of pyridine,
wherein R2-E may optionally not exist,
D and E represent independently carbon, nitrogen, oxygen or sulfur, or represent direct bond, or
R1 represents halogen;
C1-C6-alkyl optionally substituted by halogen, C3-C10-cycloalkyl, C1-C6-alkoxy, C1-C6-alkylamino, C3-C10-heterocycloalkyl or C1-C6-alkyl-C3-C10-heterocycloalkyl;
C3-C10-cycloalkyl optionally substituted by C3-C10-alkylsilanyloxy or hydroxy;
C2-C6-alkenyl;
C2-C6-alkynyl;
C3-C10-heterocycloalkyl optionally substituted by C1-C6-alkylamino or halogen;
C1-C6-alkyl-C3-C10-cycloalkyl;
C1-C6-alkyl-C3-C10-heterocycloalkyl;
aryl;
C1-C6-alkylaryl;
unsubstituted heteroaryl or C1-C6-alkyl-C5-C6-heteroaryl,
R2 represents hydrogen;
halogen;
C1-C6-alkyl optionally substituted by halogen, C3-C10-cycloalkyl, C1-C6-alkoxy, C1-C6-alkylamino, C3-C10-heterocycloalkyl or C1-C6-alkyl-C3-C10-heterocycloalkyl;
C3-C10-cycloalkyl optionally substituted by C3-C10-alkylsilanyloxy or hydroxy;
C2-C6-alkenyl;
C2-C6-alkynyl;
C3-C10-heterocycloalkyl optionally substituted by C1-C6-alkylamino or halogen;
C1-C6-alkyl-C3-C10-cycloalkyl;
C1-C6-alkyl-C3-C10-heterocycloalkyl;
aryl;
C1-C6-alkylaryl;
unsubstituted heteroaryl or C1-C6-alkyl-C5-C6-heteroaryl, and
when D and E represent nitrogen or carbon, R1 and R2 can represent two or three C1-C6-alkyl optionally substituted by C3-C10-cycloalkyl or C3-C10-heterocycloalkyl;
C3-C10-cycloalkyl;
C2-C6-alkenyl;
C2-C6-alkynyl;
C1-C6-alkyl-C3-C10-cycloalkyl;
aryl or C1-C6-alkylaryl which may be the same or different,
G represents -J-(CR5R6)p, wherein J represents oxygen or sulfur, R5 and R6 represent independently hydrogen, halogen, alkyl, cycloalkyl, hydroxyl or amine, and R5 and R6 which are substituted at the same or different carbon may be connected to form cycloalkyl,
R3 and R4 cannot independently exist depending on the number of m or n, or represent independently hydrogen, halogen, or optionally substituted C1-C6-alkyl or C1-C6-alkoxy,
R7 represents hydrogen, alkyl or cycloalkyl,
m and n represent independently an integer of 0 to 5,
p represents an integer of 2 to 6, and
wherein the isomer is at least one selected from the group consisting of an E-isomer, Z-isomer, R-isomer, S-isomer, racemic mixture and a diastereoisomer mixture.

36 more elements

Facts

Application

14/894,928Filed 26 Jun 2014

Priority

KR 10-2013-007492727 Jun 2013

Published

US 2016/0168096 A116 Jun 2016

Granted

5 Mar 2019

Term ends

Not estimatedThe source records don’t support an estimate.

Classification28 codes

C07D 213/643
Attached in position 2 or 6: 2-Phenoxypyridines; Derivatives thereof
A61P 1/16
Drugs for disorders of the alimentary tract or the digestive system: for liver or gallbladder disorders, e.g. hepatoprotective agents,…
A61P 3/00
Drugs for disorders of the metabolism
A61P 3/04
Drugs for disorders of the metabolism: anorexiants; Antiobesity agents