US 9,902,722 B2Granted

Biaryl kinase inhibitors

AssigneeBristol-Myers Squibb Company

InventorsGuanglin Luo, Ling Chen, Carolyn Diane Dzierba, Jonathan L. Ditta, John E. Macor, Joanne J. Bronson

Life of this patent

Estimating the term…

Abstract

The present disclosure is generally directed to compounds which can inhibit AAK1 (adaptor associated kinase 1), compositions comprising such compounds, and methods for inhibiting AAK1.

Claims13

Dependent claims

A compound of formula (I)

or a pharmaceutically acceptable salt thereof, wherein:
A is selected from
wherein “” denotes the point of attachment to B;
B is selected from
wherein “*” indicates the point of attachment to R5 and “**” indicates the point of attachment to ring A;
R1 is selected from hydrogen, amino, —CO2H, difluoromethyl, ethyl, halo, hydroxymethyl, methoxy, methyl, —NHC(O)CH3, —NHCO2CH3, trifluoromethoxy, and trifluoromethyl;
R2 is selected from hydrogen, cyano, —CH2OH, halo, and methyl;
R3 is selected from hydrogen, cyano, cyclopropyl, difluoromethyl, halo, hydroxymethyl, methoxy, methyl, methylsulfonyl, trifluoromethoxy, trifluoromethyl, —CH2N(CH3)2, and a five-membered aromatic ring containing one, two, or three heteroatoms selected from nitrogen, oxygen, and sulfur;
R4 is selected from hydrogen, halo, and methyl;
R5 is selected from
R6 is selected from hydrogen, ethyl, fluoromethyl, difluoromethyl, methyl, and trifluoromethyl;
and
R7 is methyl.

10 more elements

A compound selected from

(S)—N-(4-(4-((2-amino-4-methylpentyl)oxy)-3-fluorophenyl)pyridin-2-yl)acetamide;
(S)—N-(4-(4-((2-amino-4-methylpentyl)oxy)-3-methoxyphenyl)pyridin-2-yl)acetamide;
(S)—N-(4-(4-((2-amino-4-methylpentyl)oxy)-3-cyanophenyl)pyridin-2-yl)acetamide;
(S)-2-((2-amino-4-methylpentyl)oxy)-5-(2-aminopyridin-4-yl)benzonitrile;
(S)—N-(4-(4-((2-amino-4-methylpentyl)oxy)-3-(trifluoromethyl)phenyl)pyridin-2-yl)acetamide;
(S)—N-(4-(4-((2-amino-4-methylpentyl)oxy)-3-(trifluoromethoxy)phenyl)pyridin-2-yl)acetamide;
(S)—N-(4-(4-((2-amino-4-methylpentyl)oxy)-3-methylphenyl)pyridin-2-yl)acetamide;
(S)—N-(4-(4-((2-amino-4-methylpentyl)oxy)-3-chlorophenyl)pyridin-2-yl)acetamide;
(S)—N-(4-(4-((2-amino-4-methylpentyl)oxy)-3,5-difluorophenyl)pyridin-2-yl)acetamide;
(S)—N-(4-(4-((2-amino-4-methylpentyl)oxy)-3-chloro-5-fluorophenyl)pyridin-2-yl)acetamide;
(S)—N-(4-(4-((2-amino-4-methylpentyl)oxy)-3-fluoro-5-(trifluoromethyl)phenyl)pyridin-2-yl)acetamide;
(S)—N-(4-(4-((2-amino-4-methylpentyl)oxy)-2,5-difluorophenyl)pyridin-2-yl)acetamide;
(S)-methyl (4-(4-((2-amino-4-methylpentyl)oxy)-3-fluorophenyl)pyridin-2-yl)carbamate;
(S)-methyl (4-(4-((2-amino-4-methylpentyl)oxy)-3-(isoxazol-5-yl)phenyl)pyridin-2-yl)carbamate;
(S)-2-((2-amino-4-methylpentyl)oxy)-5-(2-methylpyridin-4-yl)benzonitrile;
(S)-2-((2-amino-4-methylpentyl)oxy)-5-(2-methoxypyridin-4-yl)benzonitrile;
(S)-2-((2-amino-4-methylpentyl)oxy)-5-(2-(trifluoromethyl)pyridin-4-yl)benzonitrile;
(S)-1-(2-(isoxazol-5-yl)-4-(2-methylpyridin-4-yl)phenoxy)-4-methylpentan-2-amine;
(S)—N-(4-(4-((2-amino-2,4-dimethylpentyl)oxy)-3-(trifluoromethyl)phenyl)pyridin-2-yl)acetamide;
(S)-methyl (4-(4-((2-amino-2,4-dimethylpentyl)oxy)-3-(trifluoromethyl)phenyl)pyridin-2-yl)carbamate;
(S)—N-(4-(4-((2-amino-2,4-dimethylpentyl)oxy)-3-cyanophenyl)pyridin-2-yl)acetamide;
(S)-methyl (4-(4-((2-amino-2,4-dimethylpentyl)oxy)-3-cyanophenyl)pyridin-2-yl)carbamate;
(S)—N-(4-(4-((2-amino-2,4-dimethylpentyl)oxy)-3-(difluoromethyl)phenyl)pyridin-2-yl)acetamide;
(S)-methyl (4-(4-((2-amino-2,4-dimethylpentyl)oxy)-3-(difluoromethyl)phenyl)pyridin-2-yl)carbamate;
(S)—N-(4-(4-((2-amino-2,4-dimethylpentyl)oxy)-3-(trifluoromethoxy)phenyl)pyridin-2-yl)acetamide;
(S)-methyl (4-(4-((2-amino-2,4-dimethylpentyl)oxy)-3-(trifluoromethoxy)phenyl)pyridin-2-yl)carbamate;
(S)—N-(4-(4-((2-amino-2,4-dimethylpentyl)oxy)-3-fluorophenyl)pyridin-2-yl)acetamide;
(S)-methyl (4-(4-((2-amino-2,4-dimethylpentyl)oxy)-3-fluorophenyl)pyridin-2-yl)carbamate;
methyl (4-(4-((2-amino-2,4-dimethylpentyl)oxy)-3-chlorophenyl)pyridin-2-yl)carbamate;
methyl (4-(4-((2-amino-2,4-dimethylpentyl)oxy)-3-methylphenyl)pyridin-2-yl)carbamate;
methyl (4-(4-((2-amino-2,4-dimethylpentyl)oxy)-2,3-dimethylphenyl)pyridin-2-yl)carbamate;
(S)-methyl (4-(4-((2-amino-2,4-dimethylpentyl)oxy)-3-(hydroxymethyl)phenyl)pyridin-2-yl)carbamate;
(S)-methyl (4-(4-((2-amino-2,4-dimethylpentyl)oxy)-3-cyclopropylphenyl)pyridin-2-yl)carbamate;
(S)—N-(4-(4-((2-amino-2,4-dimethylpentyl)oxy)-3-(trifluoromethyl)phenyl)-5-(hydroxymethyl)pyridin-2-yl)acetamide;
(S)-1-(4-(2-(difluoromethyl)pyridin-4-yl)-2-(trifluoromethyl)phenoxy)-2,4-dimethylpentan-2-amine;
(S)-2-((2-amino-2,4-dimethylpentyl)oxy)-5-(2-(difluoromethyl)pyridin-4-yl)benzonitrile;
(S)-1-(2-(difluoromethyl)-4-(2-(difluoromethyl)pyridin-4-yl)phenoxy)-2,4-dimethylpentan-2-amine;
(S)-1-(4-(2-(difluoromethyl)pyridin-4-yl)-2-(trifluoromethoxy)phenoxy)-2,4-dimethylpentan-2-amine;
(S)-1-(4-(3-chloro-2-fluoropyridin-4-yl)-2-(trifluoromethyl)phenoxy)-2,4-dimethylpentan-2-amine;
(S)-1-(4-(5-chloro-2-fluoropyridin-4-yl)-2-(trifluoromethyl)phenoxy)-2,4-dimethylpentan-2-amine;
(S)-1-(4-(2-fluoro-3-methylpyridin-4-yl)-2-(trifluoromethyl)phenoxy)-2,4-dimethylpentan-2-amine;
(S)-1-(4-(2,3-difluoropyridin-4-yl)-2-(trifluoromethyl)phenoxy)-2,4-dimethylpentan-2-amine;
(S)-2,4-dimethyl-1-(4-(pyridin-4-yl)-2-(trifluoromethyl)phenoxy)pentan-2-amine;
(S)-1-(4-(2-fluoropyridin-4-yl)-2-(trifluoromethyl)phenoxy)-2,4-dimethylpentan-2-amine;
(S)-2,4-dimethyl-1-(4-(2-methylpyridin-4-yl)-2-(trifluoromethyl)phenoxy)pentan-2-amine;
(S)-1-(4-(3-methoxypyridin-4-yl)-2-(trifluoromethyl)phenoxy)-2,4-dimethylpentan-2-amine;
(S)-1-(4-(3-fluoropyridin-4-yl)-2-(trifluoromethyl)phenoxy)-2,4-dimethylpentan-2-amine;
(S)-2-((2-amino-2,4-dimethylpentyl)oxy)-5-(2-methylpyridin-4-yl)benzonitrile;
(S)-1-(2-cyclopropyl-4-(2-methylpyridin-4-yl)phenoxy)-2,4-dimethylpentan-2-amine;
(S)-1-(2-(difluoromethyl)-4-(2-methylpyridin-4-yl)phenoxy)-2,4-dimethylpentan-2-amine;
methyl (6-((2-amino-2,4-dimethylpentyl)oxy)-[3,4′-bipyridin]-2′-yl)carbamate;
(S)-methyl (6-((2-amino-2,4-dimethylpentyl)oxy)-5-methyl-[3,4′-bipyridin]-2′-yl)carbamate;
(S)-methyl (6-((2-amino-2,4-dimethylpentyl)oxy)-5-cyano-[3,4′-bipyridin]-2′-yl)carbamate;
(S)-methyl (6-((2-amino-2,4-dimethylpentyl)oxy)-4-methyl-[3,4′-bipyridin]-2′-yl)carbamate;
(S)-methyl (6-((2-amino-2,4-dimethylpentyl)oxy)-5-chloro-[3,4′-bipyridin]-2′-yl)carbamate;
(S)-methyl (6-((2-amino-2,4-dimethylpentyl)oxy)-5-methoxy-[3,4′-bipyridin]-2′-yl)carbamate;
(S)-1-((2′-chloro-5-methyl-[3,4′-bipyridin]-6-yl)oxy)-2,4-dimethylpentan-2-amine;
(S)-1-((2′-(difluoromethyl)-5-methyl-[3,4′-bipyridin]-6-yl)oxy)-2,4-dimethylpentan-2-amine;
(S)-6-((2-amino-2,4-dimethylpentyl)oxy)-2′-(difluoromethyl)-[3,4′-bipyridine]-5-carbonitrile;
(S)-1-((5-chloro-2′-methyl-[3,4′-bipyridin]-6-yl)oxy)-2,4-dimethylpentan-2-amine;
(S)-1-((2′,5-dimethyl-[3,4′-bipyridin]-6-yl)oxy)-2,4-dimethylpentan-2-amine;
(S)-1-((5-methoxy-2′-methyl-[3,4′-bipyridin]-6-yl)oxy)-2,4-dimethylpentan-2-amine;
methyl (5-((2-amino-2,4-dimethylpentyl)oxy)-[2,4′-bipyridin]-2′-yl)carbamate;
(S)-methyl (5-((2-amino-2,4-dimethylpentyl)oxy)-6-methyl-[2,4′-bipyridin]-2′-yl)carbamate;
(S)-1-((2′,6-dimethyl-[2,4′-bipyridin]-5-yl)oxy)-2,4-dimethylpentan-2-amine;
(S)-methyl (5-((2-amino-2,4-dimethylpentyl)oxy)-6-chloro-[2,4′-bipyridin]-2′-yl)carbamate;
(S)-1-((6-chloro-2′-methyl-[2,4′-bipyridin]-5-yl)oxy)-2,4-dimethylpentan-2-amine;
(S)-methyl (5-((2-amino-2,4-dimethylpentyl)oxy)-4-methyl-[2,4′-bipyridin]-2′-yl)carbamate;
(S)-2,4-dimethyl-1-(4-(quinolin-4-yl)-2-(trifluoromethyl)phenoxy)pentan-2-amine;
(S)-2,4-dimethyl-1-(2-(trifluoromethyl)-4-(7-(trifluoromethyl)quinolin-4-yl)phenoxy)pentan-2-amine;
(S)-1-(4-(7-fluoroquinolin-4-yl)-2-(trifluoromethyl)phenoxy)-2,4-dimethylpentan-2-amine;
(S)-1-(4-(5,7-difluoroquinolin-4-yl)-2-(trifluoromethyl)phenoxy)-2,4-dimethylpentan-2-amine;
(S)-1-(4-(6-fluoroquinolin-4-yl)-2-(trifluoromethyl)phenoxy)-2,4-dimethylpentan-2-amine;
(S)-1-(2-cyclopropyl-4-(quinolin-4-yl)phenoxy)-2,4-dimethylpentan-2-amine;
1-(2-chloro-6-fluoro-4-(quinolin-4-yl)phenoxy)-2,4-dimethylpentan-2-amine;
(S)-1-((5-(7-fluoroquinolin-4-yl)-3-methylpyridin-2-yl)oxy)-2,4-dimethylpentan-2-amine;
(S)-2-((2-amino-2,4-dimethylpentyl)oxy)-5-(5,7-difluoroquinolin-4-yl)nicotinonitrile;
(S)-1-((3-chloro-5-(quinolin-4-yl)pyridin-2-yl)oxy)-2,4-dimethylpentan-2-amine;
(S)-1-((3-methoxy-5-(quinolin-4-yl)pyridin-2-yl)oxy)-2,4-dimethylpentan-2-amine;
(S)-2-((2-amino-2,4-dimethylpentyl)oxy)-5-(1,6-naphthyridin-4-yl)nicotinonitrile;
(S)-2,4-dimethyl-1-((2-methyl-6-(quinolin-4-yl)pyridin-3-yl)oxy)pentan-2-amine;
(S)-2,4-dimethyl-1-((4-methyl-6-(quinolin-4-yl)pyridin-3-yl)oxy)pentan-2-amine;
(S)-1-((2-chloro-6-(quinolin-4-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine;
(S)-1-(4-(1H-pyrrolo[2,3-b]pyridin-4-yl)-2-(trifluoromethyl)phenoxy)-2,4-dimethylpentan-2-amine;
(S)-1-(4-(1,6-naphthyridin-4-yl)-2-(trifluoromethyl)phenoxy)-2,4-dimethylpentan-2-amine;
(S)-2-((2-amino-2,4-dimethylpentyl)oxy)-5-(1,6-naphthyridin-4-yl)benzonitrile;
(S)-2-((2-amino-2,4-dimethylpentyl)oxy)-5-(1,5-naphthyridin-4-yl)benzonitrile;
(S)-1-(4-(7-chloroquinolin-4-yl)-2-(trifluoromethyl)phenoxy)-2,4-dimethylpentan-2-amine;
(S)-4-(4-((2-amino-2,4-dimethylpentyl)oxy)-3-(trifluoromethyl)phenyl)quinoline-7-carbonitrile;
(S)-2,4-dimethyl-1-(2-methyl-4-(2-methylpyridin-4-yl)phenoxy)pentan-2-amine;
(S)-1-(2-fluoro-4-(2-methylpyridin-4-yl)phenoxy)-2,4-dimethylpentan-2-amine;
(S)-1-(4-(2-fluoropyridin-4-yl)-2-methylphenoxy)-2,4-dimethylpentan-2-amine;
(S)-1-(2-fluoro-4-(2-fluoropyridin-4-yl)phenoxy)-2,4-dimethylpentan-2-amine;
(S)-2-((2-amino-2,4-dimethylpentyl)oxy)-5-(2-fluoropyridin-4-yl)benzonitrile;
(S)-1-((2′-fluoro-5-methyl-[3,4′-bipyridin]-6-yl)oxy)-2,4-dimethylpentan-2-amine;
(S)-4-(6-((2-amino-2,4-dimethylpentyl)oxy)-5-methylpyridin-3-yl)quinoline-7-carbonitrile;
(S)-1-((5-fluoro-2′-methyl-[3,4′-bipyridin]-6-yl)oxy)-2,4-dimethylpentan-2-amine;
(S)-1-((3-fluoro-5-(quinolin-4-yl)pyridin-2-yl)oxy)-2,4-dimethylpentan-2-amine;
(S)-4-(6-((2-amino-2,4-dimethylpentyl)oxy)-5-fluoropyridin-3-yl)quinoline-7-carbonitrile;
(S)-methyl (4-(4-((2-amino-2,4-dimethylpentyl)oxy)-3-cyanophenyl)-3-fluoropyridin-2-yl)carbamate;
(S)-6-((2-amino-2,4-dimethylpentyl)oxy)-2′-methyl-[3,4′-bipyridine]-5-carbonitrile;
(S)-2-((2-amino-2,4-dimethylpentyl)oxy)-5-(7-methylquinolin-4-yl)benzonitrile;
(S)-2-((2-amino-2,4-dimethylpentyl)oxy)-5-(3-fluoro-2-methylpyridin-4-yl)benzonitrile;
(S)-2-((2-amino-2,4-dimethylpentyl)oxy)-5-(quinolin-4-yl)benzonitrile;
(S)-2-((2-amino-2,4-dimethylpentyl)oxy)-5-(5-fluoro-2-methylpyridin-4-yl)benzonitrile;
(S)-methyl (4-(4-((2-amino-2,4-dimethylpentyl)oxy)-3-cyanophenyl)-5-fluoropyridin-2-yl)carbamate;
(S)-1-((6-fluoro-2′,4-dimethyl-[2,4′-bipyridin]-5-yl)oxy)-2,4-dimethylpentan-2-amine;
methyl (5-((3-isobutylazetidin-3-yl)methoxy)-6-methyl-[2,4′-bipyridin]-2′-yl)carbamate;
(S)-2-((2-amino-4-methylpentyl)oxy)-5-(6-methylpyridazin-4-yl)benzonitrile;
(S)-1-(2-(isoxazol-5-yl)-4-(quinolin-4-yl)phenoxy)-4-methylpentan-2-amine;
(S)-4-(4-((2-amino-2,4-dimethylpentyl)oxy)-3-(trifluoromethyl)phenyl)-2-methylnicotinic acid;
(S)-methyl (4-(4-((2-amino-2,4-dimethylpentyl)oxy)-3-((dimethylamino)methyl)phenyl)pyridin-2-yl)carbamate;
(S)-methyl (4-(4-((2-amino-2,4-dimethylpentyl)oxy)-3-(methylsulfonyl)phenyl)pyridin-2-yl)carbamate;
(S)-2,4-dimethyl-1-(4-(2-methylpyridin-4-yl)-2-(methylsulfonyl)phenoxy)pentan-2-amine;
(S)-2,4-dimethyl-1-(2-(methylsulfonyl)-4-(quinolin-4-yl)phenoxy)pentan-2-amine;
(S)-1-(2-(difluoromethyl)-4-(6-fluoroquinolin-4-yl)phenoxy)-2,4-dimethylpentan-2-amine;
(S)-methyl (5-((2-amino-2,4-dimethylpentyl)oxy)-6-(difluoromethyl)-[2,4′-bipyridin]-2′-yl)carbamate;
(S)-1-(2-(difluoromethyl)-6-(quinolin-4-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine;
(S)-1-((6-(difluoromethyl)-2′-methyl-[2,4′-bipyridin]-5-yl)oxy)-2,4-dimethylpentan-2-amine;
(S)-methyl (5-((2-amino-2,4-dimethylpentyl)oxy)-4-(difluoromethyl)-[2,4′-bipyridin]-2′-yl)carbamate;
(S)-1-((4-(difluoromethyl)-6-(quinolin-4-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine;
(S)-1-((4-(difluoromethyl)-2′-methyl-[2,4′-bipyridin]-5-yl)oxy)-2,4-dimethylpentan-2-amine;
(S)-1-((2′,6-bis(difluoromethyl)-[2,4′-bipyridin]-5-yl)oxy)-2,4-dimethylpentan-2-amine;
(S)-1-((2′,4-bis(difluoromethyl)-[2,4′-bipyridin]-5-yl)oxy)-2,4-dimethylpentan-2-amine;
(S)-1-((2′-(difluoromethyl)-4-methyl-[2,4′-bipyridin]-5-yl)oxy)-2,4-dimethylpentan-2-amine;
(S)-1-(2-cyclopropyl-4-(2-(difluoromethyl)pyridin-4-yl)phenoxy)-2,4-dimethylpentan-2-amine;
(S)-1-((2-(difluoromethyl)-6-(6-fluoroquinolin-4-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine;
(S)-1-((2-(difluoromethyl)-6-(7-fluoroquinolin-4-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine;
(S)-1-((2-(difluoromethyl)-6-(5,7-difluoroquinolin-4-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine;
(S)-1-((4-(difluoromethyl)-6-(5,7-difluoroquinolin-4-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine;
(S)-1-((4-(difluoromethyl)-6-(7-fluoroquinolin-4-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine;
(S)-1-((4-(difluoromethyl)-6-(6-fluoroquinolin-4-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine;
((S)-1-((4-(difluoromethyl)-6-(6-(trifluoromethyl)quinolin-4-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine;
(S)-1-((4-(difluoromethyl)-6-(6-(trifluoromethoxy)quinolin-4-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine;
(S)-1-((2-chloro-6-(5,7-difluoroquinolin-4-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine;
(S)-1-((2-chloro-6-(7-fluoroquinolin-4-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine;
(S)-1-((6-(7-fluoroquinolin-4-yl)-2-methylpyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine;
(S)-1-((6-(6-fluoroquinolin-4-yl)-2-methylpyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine;
(S)-1-((2-(difluoromethyl)-6-(2-methylpyrimidin-4-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine;
(S)-1-((2-(difluoromethyl)-6-(6-methylpyrimidin-4-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine;
(S)-1-((4-(difluoromethyl)-2′-ethyl-[2,4′-bipyridin]-5-yl)oxy)-2,4-dimethylpentan-2-amine;
(S)-1-((2′-chloro-4-(difluoromethyl)-3′-fluoro-[2,4′-bipyridin]-5-yl)oxy)-2,4-dimethylpentan-2-amine;
(S)-1-((2′-chloro-4-(difluoromethyl)-5′-fluoro-[2,4′-bipyridin]-5-yl)oxy)-2,4-dimethylpentan-2-amine;
(S)-2,4-dimethyl-1-((2′-methyl-4-(trifluoromethyl)-[2,4′-bipyridin]-5-yl)oxy)pentan-2-amine;
(S)-2,4-dimethyl-1-((6-(quinolin-4-yl)-4-(trifluoromethyl)pyridin-3-yl)oxy)pentan-2-amine;
(S)-methyl (5-((2-amino-2,4-dimethylpentyl)oxy)-4-(trifluoromethyl)-[2,4′-325 bipyridin]-2′-yl)carbamate;
(S)-1-((2′-chloro-4-(difluoromethyl)-[2,4′-bipyridin]-5-yl)oxy)-2,4-dimethylpentan-2-amine;
(S)-1-((4-(difluoromethyl)-5′-fluoro-2′-methyl-[2,4′-bipyridin]-5-yl)oxy)-2,4-dimethylpentan-2-amine;
(S)-1-((4-(difluoromethyl)-3′-fluoro-2′-methyl-[2,4′-bipyridin]-5-yl)oxy)-2,4-dimethylpentan-2-amine;
(S)-1-((4-(difluoromethyl)-6-(2-methylpyrimidin-4-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine;
(S)-1-(2-(difluoromethyl)-4-(2-methylpyrimidin-4-yl)phenoxy)-2,4-dimethylpentan-2-amine;
(S)-5-((2-amino-2,4-dimethylpentyl)oxy)-3′-fluoro-6-methyl-[2,4′-bipyridin]-2′-amine;
(S)-1-((2′-chloro-3′-fluoro-6-methyl-[2,4′-bipyridin]-5-yl)oxy)-2,4-dimethylpentan-2-amine;
(S)-methyl (5-((2-amino-2,4-dimethylpentyl)oxy)-5′-fluoro-6-methyl-[2,4′-bipyridin]-2′-yl)carbamate;
(S)-1-((2′-chloro-5′-fluoro-6-methyl-[2,4′-bipyridin]-5-yl)oxy)-2,4-dimethylpentan-2-amine;
(S)-methyl (5-((2-amino-2,4-dimethylpentyl)oxy)-3′-fluoro-6-methyl-[2,4′-bipyridin]-2′-yl)carbamate;
(S)-1-((2′-chloro-6-(difluoromethyl)-[2,4′-bipyridin]-5-yl)oxy)-2,4-dimethylpentan-2-amine;
(S)-1-((2′-chloro-6-(difluoromethyl)-3′-fluoro-[2,4′-bipyridin]-5-yl)oxy)-2,4-dimethylpentan-2-amine;
(S)-1-((6-(difluoromethyl)-3′-fluoro-2′-methyl-[2,4′-bipyridin]-5-yl)oxy)-2,4-dimethylpentan-2-amine;
((S)-1-((6-chloro-2′-(difluoromethyl)-[2,4′-bipyridin]-5-yl)oxy)-2,4-dimethylpentan-2-amine;
(S)-1-((4-(difluoromethyl)-6-(6-methylpyridazin-4-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine;
(S)-1-((2-(difluoromethyl)-6-(6-methylpyridazin-4-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine;
(R)-2,4-dimethyl-1-((2′-methyl-4-(trifluoromethyl)-[2,4′-bipyridin]-5-yl)oxy)pentan-2-amine;
(R)-2,4-dimethyl-1-((6-(quinolin-4-yl)-4-(trifluoromethyl)pyridin-3-yl)oxy)pentan-2-amine;
(R)-methyl (5-((2-amino-2,4-dimethylpentyl)oxy)-4-(trifluoromethyl)-[2,4′-bipyridin]-2′-yl)carbamate;
(R)-1-((2′-chloro-4-(difluoromethyl)-3′-fluoro-[2,4′-bipyridin]-5-yl)oxy)-2,4-dimethylpentan-2-amine;
(R)-1-((2′-chloro-4-(difluoromethyl)-5′-fluoro-[2,4′-bipyridin]-5-yl)oxy)-2,4-dimethylpentan-2-amine;
(R)-1-((2′-chloro-4-(difluoromethyl)-[2,4′-bipyridin]-5-yl)oxy)-2,4-dimethylpentan-2-amine;
(R)-1-((4-(difluoromethyl)-2′-ethyl-[2,4′-bipyridin]-5-yl)oxy)-2,4-dimethylpentan-2-amine;
(R)-1-((4-(difluoromethyl)-5′-fluoro-2′-methyl-[2,4′-bipyridin]-5-yl)oxy)-2,4-dimethylpentan-2-amine;
(R)-1-((4-(difluoromethyl)-3′-fluoro-2′-methyl-[2,4′-bipyridin]-5-yl)oxy)-2,4-dimethylpentan-2-amine;
(R)-methyl (5-((2-amino-2,4-dimethylpentyl)oxy)-6-methyl-[2,4′-bipyridin]-2′-yl)carbamate;
(R)-1-((2′,6-bis(difluoromethyl)-[2,4′-bipyridin]-5-yl)oxy)-2,4-dimethylpentan-2-amine;
(R)-1-((2′,4-bis(difluoromethyl)-[2,4′-bipyridin]-5-yl)oxy)-2,4-dimethylpentan-2-amine;
(S)-methyl (4-(difluoromethyl)-5-((2-hydroxy-2,4-dimethylpentyl)oxy)-[2,4′-bipyridin]-2′-yl)carbamate;
(S)-1-((4-(difluoromethyl)-2′-methyl-[2,4′-bipyridin]-5-yl)oxy)-2,4-dimethylpentan-2-ol;
(S)-methyl (5-((2-amino-2-(fluoromethyl)-4-methylpentyl)oxy)-6-(difluoromethyl)-[2,4′-bipyridin]-2′-yl)carbamate;
(R)-methyl (5-((2-amino-2-(fluoromethyl)-4-methylpentyl)oxy)-6-(difluoromethyl)-[2,4′-bipyridin]-2′-yl)carbamate;
(S)-methyl (5-((2-amino-2-(fluoromethyl)-4-methylpentyl)oxy)-4-(difluoromethyl)-[2,4′-bipyridin]-2′-yl)carbamate;
(R)-methyl (5-((2-amino-2-(fluoromethyl)-4-methylpentyl)oxy)-4-(difluoromethyl)-[2,4′-bipyridin]-2′-yl)carbamate;
(S)-1-((2′,6-bis(difluoromethyl)-[2,4′-bipyridin]-5-yl)oxy)-2-(fluoromethyl)-4-methylpentan-2-amine;
(S)-1-((2′,4-bis(difluoromethyl)-[2,4′-bipyridin]-5-yl)oxy)-2-(fluoromethyl)-4-methylpentan-2-amine;
(R)-1-((2′,6-bis(difluoromethyl)-[2,4′-bipyridin]-5-yl)oxy)-2-(fluoromethyl)-4-methylpentan-2-amine;
(R)-1-((2′,4-bis(difluoromethyl)-[2,4′-bipyridin]-5-yl)oxy)-2-(fluoromethyl)-4-methylpentan-2-amine;
(S)-1-((4-(difluoromethyl)-2′-methyl-[2,4′-bipyridin]-5-yl)oxy)-2-(fluoromethyl)-4-methylpentan-2-amine;
(R)-1-((4-(difluoromethyl)-2′-methyl-[2,4′-bipyridin]-5-yl)oxy)-2-(fluoromethyl)-4-methylpentan-2-amine;
(S)—N-(4-(4-((2-amino-4-methylpentyl)oxy)-3-fluorophenyl)pyridin-2-yl)acetamide;
(S)-1-((3-chloro-5-(7-fluoroquinolin-4-yl)pyridin-2-yl)oxy)-2,4-dimethylpentan-2-amine;
(S)-1-((3-chloro-5-(6-fluoroquinolin-4-yl)pyridin-2-yl)oxy)-2,4-dimethylpentan-2-amine;
(S)-1-((3-chloro-5-(2-methylpyrimidin-4-yl)pyridin-2-yl)oxy)-2,4-dimethylpentan-2-amine;
(S)-1-((2′-chloro-5-(difluoromethyl)-[3,4′-bipyridin]-6-yl)oxy)-2,4-dimethylpentan-2-amine;
(S)-1-((5-(difluoromethyl)-2′-methyl-[3,4′-bipyridin]-6-yl)oxy)-2,4-dimethylpentan-2-amine;
(S)-1-((3-(difluoromethyl)-5-(7-fluoroquinolin-4-yl)pyridin-2-yl)oxy)-2,4-dimethylpentan-2-amine;
(S)-methyl (6-((2-amino-2,4-dimethylpentyl)oxy)-5-(difluoromethyl)-[3,4′-bipyridin]-2′-yl)carbamate;
(S)-1-((5-(7-chloroquinolin-4-yl)-3-(difluoromethyl)pyridin-2-yl)oxy)-2,4-dimethylpentan-2-amine;
(S)-1-((3-(difluoromethyl)-5-(2-methylpyrimidin-4-yl)pyridin-2-yl)oxy)-2,4-dimethylpentan-2-amine;
(S)-1-((2′,5-bis(difluoromethyl)-[3,4′-bipyridin]-6-yl)oxy)-2,4-dimethylpentan-2-amine;
(S)-1-((3-(difluoromethyl)-5-(6-fluoroquinolin-4-yl)pyridin-2-yl)oxy)-2,4-dimethylpentan-2-amine;
(S)-1-((3-(difluoromethyl)-5-(5,7-difluoroquinolin-4-yl)pyridin-2-yl)oxy)-2,4-dimethylpentan-2-amine;
(5)-1-((3-(difluoromethyl)-5-(7-(trifluoromethyl)quinolin-4-yl)pyridin-2-yl)oxy)-2,4-dimethylpentan-2-amine;
(5)-1-((5-(difluoromethyl)-2′,3′-dimethyl-[3,4′-bipyridin]-6-yl)oxy)-2,4-dimethylpentan-2-amine;
(5)-1-((3-(difluoromethyl)-5-(quinolin-4-yl)pyridin-2-yl)oxy)-2,4-dimethylpentan-2-amine;
(5)-1-((3-(difluoromethyl)-5-(7-methylquinolin-4-yl)pyridin-2-yl)oxy)-2,4-dimethylpentan-2-amine;
(S)-methyl (5-((2-amino-2,4-dimethylpentyl)oxy)-4-methoxy-[2,4′-bipyridin]-2′-yl)carbamate;
(S)-1-((2′-(difluoromethyl)-4-methoxy-[2,4′-bipyridin]-5-yl)oxy)-2,4-dimethylpentan-2-amine;
(S)-methyl (4-(4-((2-amino-2,4-dimethylpentyl)oxy)naphthalen-1-yl)pyridin-2-yl)carbamate;
(S)-2,4-dimethyl-1-((4-(quinolin-4-yl)naphthalen-1-yl)oxy)pentan-2-amine;
(S)-methyl (4-(5-((2-amino-2,4-dimethylpentyl)oxy)pyrimidin-2-yl)pyridin-2-yl)carbamate;
(S)-methyl (4-(2-((2-amino-2,4-dimethylpentyl)oxy)pyrimidin-5-yl)pyridin-2-yl)carbamate;
(S)-2,4-dimethyl-1-((2′,4,6-trimethyl-[2,4′-bipyridin]-5-yl)oxy)pentan-2-amine;
(S)-methyl (5-((2-amino-2,4-dimethylpentyl)oxy)-4,6-dimethyl-[2,4′-bipyridin]-2′-yl)carbamate;
(S)-2,4-dimethyl-1-(4-(quinazolin-4-yl)-2-(trifluoromethyl)phenoxy)pentan-2-amine;
(S)-1-(4-(3,6-dihydro-2H-pyran-4-yl)-2-(trifluoromethyl)phenoxy)-2,4-dimethylpentan-2-amine;
(S)-2,4-dimethyl-1-(4-(2-methylquinolin-4-yl)-2-460 (trifluoromethyl)phenoxy)pentan-2-amine;
(S)-1-(4-(6-chloroquinolin-4-yl)-2-(trifluoromethyl)phenoxy)-2,4-dimethylpentan-2-amine;
(S)-1-((5-(5,7-difluoroquinolin-4-yl)-3-(trifluoromethyl)pyridin-2-yl)oxy)-2,4-dimethylpentan-2-amine;
(S)-2,4-dimethyl-1-((5-(quinolin-4-yl)-3-(trifluoromethyl)pyridin-2-yl)oxy)pentan-2-amine;
(S)-methyl (6-((2-amino-2,4-dimethylpentyl)oxy)-5-(trifluoromethyl)-[3,4′-bipyridin]-2′-yl)carbamate;
(S)-2,4-dimethyl-1-((2′-methyl-5-(trifluoromethyl)-[3,4′-bipyridin]-6-yl)oxy)pentan-2-amine;
(S)-1-((5-(6-chloroquinolin-4-yl)-3-methylpyridin-2-yl)oxy)-2,4-dimethylpentan-2-amine;
(S)-1-((5-(6-fluoroquinolin-4-yl)-3-methylpyridin-2-yl)oxy)-2,4-dimethylpentan-2-amine;
(S)-1-((5-(5,7-difluoroquinolin-4-yl)-3-methylpyridin-2-yl)oxy)-2,4-dimethylpentan-2-amine;
(S)-1-((5-(7-chloroquinolin-4-yl)-3-methylpyridin-2-yl)oxy)-2,4-dimethylpentan-2-amine;
(S)-1-((6-(5,7-difluoroquinolin-4-yl)-4-methylpyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine;
(S)-1-((6-(7-fluoroquinolin-4-yl)-4-methylpyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine;
(S)-1-((2′,4-dimethyl-[2,4′-bipyridin]-5-yl)oxy)-2,4-dimethylpentan-2-amine;
(S)-1-((6-(6-chloroquinolin-4-yl)-4-methylpyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine;
(S)-1-((6-(6-fluoroquinolin-4-yl)-4-methylpyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine;
(S)-1-((6-(7-chloroquinolin-4-yl)-4-methylpyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine;
(S)-1-((6-(7-fluoroquinolin-4-yl)-4-methylpyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine;
(S)-1-((4-chloro-6-(5,7-difluoroquinolin-4-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine;
(S)-1-((4-chloro-[2,4′-bipyridin]-5-yl)oxy)-2,4-dimethylpentan-2-amine;
(S)-1-((4-chloro-6-(6-fluoroquinolin-4-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine;
(S)-1-((4-chloro-6-(quinolin-4-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine;
(S)-methyl (5-((2-amino-2,4-dimethylpentyl)oxy)-4-chloro-[2,4′-bipyridin]-2′-yl)carbamate;
(S)-1-((4-chloro-2′-methyl-[2,4′-bipyridin]-5-yl)oxy)-2,4-dimethylpentan-2-amine;
(S)-1-((4-chloro-6-(6-chloroquinolin-4-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine;
(S)-1-((2′,4-dichloro-[2,4′-bipyridin]-5-yl)oxy)-2,4-dimethylpentan-2-amine;
(S)-1-((4-chloro-6-(7-fluoroquinolin-4-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine;
(S)-1-((4-chloro-6-(7-(trifluoromethyl)quinolin-4-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine;
(S)-1-((4-chloro-2′,3′-dimethyl-[2,4′-bipyridin]-5-yl)oxy)-2,4-dimethylpentan-2-amine;
(S)-1-((5-(difluoromethyl)-2′-methyl-[3,4′-bipyridin]-6-yl)oxy)-2,4-dimethylpentan-2-amine;
(R)-methyl (6-((2-amino-2,4-dimethylpentyl)oxy)-5-(difluoromethyl)-[3,4′-bipyridin]-2′-yl)carbamate;
(R)-1-((3-(difluoromethyl)-5-(quinolin-4-yl)pyridin-2-yl)oxy)-2,4-dimethylpentan-2-amine;
(R)-1-((3-(difluoromethyl)-5-(2-methylpyrimidin-4-yl)pyridin-2-yl)oxy)-2,4-dimethylpentan-2-amine;
(R)-1-((3-(difluoromethyl)-5-(5,7-difluoroquinolin-4-yl)pyridin-2-yl)oxy)-2,4-dimethylpentan-2-amine;
(R)-1-((5-(7-chloroquinolin-4-yl)-3-(difluoromethyl)pyridin-2-yl)oxy)-2,4-dimethylpentan-2-amine;
and
N-(4′-((2-amino-2,4-dimethylpentyl)oxy)-3′-methyl-[1,1′-biphenyl]-3-yl)acetamide;
or a pharmaceutically acceptable salt thereof.

247 more elements

Dependencies are inferred from the claim text.

Facts

Application: 15/300,618Filed 1 Apr 2015 · us provisional application
Priority: 2 Apr 2014
Published: US 2017/0183340 A129 Jun 2017
Granted: 27 Feb 2018
Term ends: Not estimatedThe source records don’t support an estimate.

Classification26 codes

C07D 471/04
In which the condensed system contains two hetero rings: ortho-condensed systems
A61K 31/4427
Non condensed pyridines; Hydrogenated derivatives thereof: containing further heterocyclic ring systems
A61K 31/50
Having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines: pyridazines; Hydrogenated…
A61P 25/28
Drugs for disorders of the nervous system: for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents,…

Family

Application61/973,942Us provisional application · filed 2 Apr 2014
Application62/061,591Us provisional application · filed 8 Oct 2014
US 2017/0183340 A1Pre-grant publication · published 29 Jun 2017
US 9,902,722 B2This patent

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

Timeline

Citations

Open elsewhere

patentgrep

Loading patent…

Abstract

The present disclosure is generally directed to compounds which can inhibit AAK1 (adaptor associated kinase 1), compositions comprising such compounds, and methods for inhibiting AAK1.

Facts

Application

15/300,618Filed 1 Apr 2015 · us provisional application

Priority

2 Apr 2014

Published

US 2017/0183340 A129 Jun 2017

Granted

27 Feb 2018

Term ends

Not estimatedThe source records don’t support an estimate.

Classification26 codes

C07D 471/04
In which the condensed system contains two hetero rings: ortho-condensed systems
A61K 31/4427
Non condensed pyridines; Hydrogenated derivatives thereof: containing further heterocyclic ring systems
A61K 31/50
Having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines: pyridazines; Hydrogenated…
A61P 25/28
Drugs for disorders of the nervous system: for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents,…