Fluorinated lysyl oxidase-like 2 inhibitors and uses thereof
First Claim
Patent Images
1. A compound of Formula (VI), or a pharmaceutically acceptable salt thereof:
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Abstract
Described herein are compounds that are LOXL2 inhibitors, methods of making such compounds, pharmaceutical compositions and medicaments comprising such compounds, and methods of using such compounds in the treatment of conditions, diseases, or disorders associated with LOXL2 activity.
47 Citations
24 Claims
- 1. A compound of Formula (VI), or a pharmaceutically acceptable salt thereof:
- 12. A compound that has the following structure, or a pharmaceutically acceptable salt thereof:
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16. A compound that has the following structure, or a pharmaceutically acceptable salt thereof:
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17. A compound that is:
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(2-([1,1′
-Biphenyl]-3-yloxy)-6-(trifluoromethyl)pyridin-4-yl)methanamine;(2-(3-Phenoxyphenoxy)-6-(trifluoromethyl)pyridin-4-yl)methanamine; (2-(3-(Phenoxymethyl)phenoxy)-6-(trifluoromethyl)pyridin-4-yl)methanamine; 3-((4-(Aminomethyl)-6-(trifluoromethyl)pyridin-2-yl)oxy)-N-phenylaniline; (2-(3-(1H-Pyrazol-4-yl)phenoxy)-6-(trifluoromethyl)pyridin-4-yl)methanamine; 3-((4-(Aminomethyl)-6-(trifluoromethyl)pyridin-2-yl)oxy)-N-phenylbenzamide; 3-((4-(Aminomethyl-d2)-6-(trifluoromethyl)pyridin-2-yl)oxy)-N-phenylbenzamide; 3-((4-(Aminomethyl)-6-(trifluoromethyl)pyridin-2-yl)oxy)-N-(4-fluorobenzyl)benzamide; 3-((4-(Aminomethyl)-6-(trifluoromethyl)pyridin-2-yl)oxy)-N-(benzo[b]thiophen-2-ylmethyl)benzamide; (3-((4-(Aminomethyl)-6-(trifluoromethyl)pyridin-2-yl)oxy)phenyl)(3,4-dihydroisoquinolin-2(1H)-yl)methanone; (3-(1H-Pyrazol-1-yl)azetidin-1-yl)(3-((4-(aminomethyl)-6-(trifluoromethyl)pyridin-2-yl)oxy)phenyl)methanone; N-((2H-Tetrazol-5-yl)methyl)-3-((4-(aminomethyl)-6-(trifluoromethyl)pyridin-2-yl)oxy)benzamide; N-(2-(1H-1,2,4-Triazol-1-yl)ethyl)-3-((4-(aminomethyl)-6-(trifluoromethyl)pyridin-2-yl)oxy)benzamide; N-(2-(1H-Tetrazol-1-yl)ethyl)-3-((4-(aminomethyl)-6-(trifluoromethyl)pyridin-2-yl)oxy)benzamide; 3-((4-(Aminomethyl)-6-(trifluoromethyl)pyridin-2-yl)oxy)-N-(2-hydroxyethyl)benzamide; (S)-(3-((4-(Aminomethyl)-6-(trifluoromethyl)pyridin-2-yl)oxy)phenyl)(3-hydroxypyrrolidin-1-yl)methanone; (R)-(3-((4-(Aminomethyl)-6-(trifluoromethyl)pyridin-2-yl)oxy)phenyl)(3-hydroxypyrrolidin-1-yl)methanone; Racemic-trans-(3-((4-(aminomethyl)-6-(trifluoromethyl)pyridin-2-yl)oxy)phenyl)(3-fluoro-4-hydroxypyrrolidin- 1-yl)methanone; (S,S)-trans-(3-((4-(Aminomethyl)-6-(trifluoromethyl)pyridin-2-yl)oxy)phenyl)(3-fluoro-4-hydroxypyrrolidin- 1-yl)methanone; (R,R)-trans-(3-((4-(Aminomethyl)-6-(trifluoromethyl)pyridin-2-yl)oxy)phenyl)(3-fluoro-4-hydroxypyrrolidin- 1-yl)methanone; (R)-(3-((4-(Aminomethyl)-6-(trifluoromethyl(pyridin-2-yl)oxy)phenyl)(3-aminopyrrolidin-1-yl)methanone; Racemic-trans-(3-((4-(aminomethyl)-6-(trifluoromethyl)pyridin-2-yl)oxy)phenyl)(-3-(dimethylamino)-4-hydroxypyrrolidin-1-yl)methanone; (S)-1-(3-((4-(Aminomethyl)-6-(trifluoromethyl)pyridin-2-yl)oxy)benzoyl)pyrrolidine-2-carboxylic acid; (R)-1-(3-((4-(Aminomethyl)-6-(trifluoromethyl)pyridin-2-yl)oxy)benzoyl)pyrrolidine-2-carboxylic acid; (R)-(3-((4-(Aminomethyl)-6-(trifluoromethyl)pyridin-2-yl)oxy)phenyl)(3-(hydroxymethyl)pyrrolidin-1-yl)methanone; 8-(3-((4-(Aminomethyl)-6-(trifluoromethyl)pyridin-2-yl)oxy)benzoyl)-1-oxa-3,8-diazaspiro[4.5]decan-2-one; 3-((4-(Aminomethyl)-6-(trifluoromethyl)pyridin-2-yl)oxy)-N-(2-(2-oxooxazolidin-3-yl)ethyl)benzamide; Racemic-3-((4-(aminomethyl)-6-(trifluoromethyl)pyridin-2-yl)oxy)-N-((5oxopyrrolidin-2-yl)methyl)benzamide; 3-((4-(Aminomethyl)-6-(trifluoromethyl)pyridin-2-yl)oxy)-N-(2-(methylsulfonyl)ethyl)benzamide; 3-((4-(Aminomethyl)-6-(trifluoromethyl)pyridin-2-yl)oxy)-N-(1-(hydroxymethyl)cyclopropyl)benzamide; 3-((4-(Aminomethyl)-6-(trifluoromethyl)pyridin-2-yl)oxy)-N-(2-hydroxy-2-methylpropyl)benzamide; (R)-3-((4-(Aminomethyl)-6-(trifluoromethyl)pyridin-2-yl)oxy)-N-(2,3-dihydroxypropyl)benzamide; 3-((4-(Aminomethyl)-6-(trifluoromethyl)pyridin-2-yl)oxy)-N-(2-sulfamoylethyl)benzamide; 3-((4-(Aminomethyl)-6-(trifluoromethyl)pyridin-2-yl)oxy)-N-(2-(dimethylamino)ethyl)benzamide; Racemic-trans-(3-(((4-(aminomethyl)-6-(trifluoromethyl)pyridin-2-yl)oxy)methyl)phenyl)(3-fluoro-4-hydroxypyrrolidin-1-yl)methanone; 3-((4-(Aminomethyl)-6-(trifluoromethyl)pyridin-2-yl)thio)-N-phenylbenzamide; 3-(((4-(Aminomethyl)-6-(trifluoromethyl)pyridin-2-yl)amino)methyl)-N-phenylbenzamide; 3-(((4-(Aminomethyl)-6-(trifluoromethyl)pyridin-2-yl)amino)methyl)-N-(2-(methylsulfonyl)ethyl)benzamide; 1-(3-((4-(Aminomethyl)-6-(trifluoromethyl)pyridin-2-yl)oxy)phenyl)pyridin-2(1H )-one; 3-((4-(Aminomethyl)-6-(trifluoromethyl)pyridin-2-yl)oxy)-N-(2-cyanoethyl)benzamide; 1-(3-((4-(Aminomethyl)-6-(trifluoromethyl)pyridin-2-yl)oxy)benzoyl)azetidin-3-carbonitrile; 3-((4-(Aminomethyl)-6-(trifluoromethyl)pyridin-2-yl)oxy)-N-(oxetan-3-yl)benzamide; 3-((4-(Aminomethyl)-6-(trifluoromethyl)pyridin-2-yl)oxy)-N-((1-hydroxycyclobutyl)methyl)benzamide; 3-((4-(Aminomethyl)-6-(trifluoromethyl)pyridin-2-yl)oxy)-N-(2-hydroxyethyl)-N-methylbenzamide; (S)-(3-((4-(Aminomethyl)-6-(trifluoromethyl)pyridin-2-yl)oxy)phenyl)(3-(hydroxyethyl)piperidin-1-yl)methanone; (3-((4-(Aminomethyl)-6-(trifluoromethyl)pyridin-2-yl)oxy)phenyl)(4-(hydroxymethyl)piperidin-1-yl)methanone; (3-((4-(Aminomethyl)-6-(trifluoromethyl)pyridin-2-yl)oxy)phenyl)(4-hydroxy-4-methylpiperidin-1-yl)methanone; (3-((4-(Aminomethyl)-6-(trifluoromethyl)pyridin-2-yl)oxy)phenyl)(3-(methoxymethyl)azetidin-1-yl)methanone; (3-((4-(Aminomethyl)-6-(trifluoromethyl)pyridin-2-yl)oxy)phenyl)(7-oxa-2-azaspiro[3.5]nonan-2-yl)methanone; 3-((4-(Aminomethyl)-6-(trifluoromethyl)pyridin-2-yl)oxy)-N-((3S,4S)-4-hydroxytetrahydro-2H-pyran-3-yl)benzamide; 3-((4-(Aminomethyl)-6-(trifluoromethyl)pyridin-2-yl)oxy)-N-((1R,2S)-2-hydroxycyclopentyl)benzamide; 3-((4-(Aminomethyl)-6-(trifluoromethyl)pyridin-2-yl)oxy)-N-((1S,2R)-2-hydroxycyclopentyl)benzamide; Racemic-cis-(3-((4-(aminomethyl)-6-(trifluoromethyl)pyridin-2-yl)oxy)phenyl)(3-fluoro-4-hydroxypyrrolidin-1-yl)methanone; (R)-(3-((4-(Aminomethyl)-6-(trifluoromethyl)pyridin-2-yl)oxy)phenyl)(3 -fluoropyrrolidin-1-yl)methanone; (S)-(3-((4-(Aminomethyl)-6-(trifluoromethyl)pyridin-2-yl)oxy)phenyl)(3-fluoropyrrolidin-1-yl)methanone; (3R,4R)-1-(3-((4-(Aminomethyl)-6-(trifluoromethyl)pyridin-2-yl)oxy)benzoyl)-4-fluoropyrrolidin-3-ylmethanesulfonate; (3-((4-(Aminomethyl)-6-(trifluoromethyl)pyridin-2-yl)oxy)phenyl)(2,5-dihydro-1H-pyrrol-1-yl)methanone; 3-((4-(Aminomethyl)-6-(trifluoromethyl)pyridin-2-yl)oxy)-N-(hex-5-yn-1-yl)benzamide; 3-((4-(Aminomethyl)-6-(trifluoromethyl)pyridin-2-yl)oxy)-N-(4-(1-phenyl-1H-1,2,3-triazol-4-yl)butyl)benzamide; 3-((4-(Aminomethyl)-6-(trifluoromethyl)pyridin-2-yl)oxy)-N-hydroxybenzamide; 3-((4-(Aminomethyl)-6-(trifluoromethyl)pyridin-2-yl)oxy)-N-methoxybenzamide; Methyl(S)-3-(3-((4-(aminomethyl)-6-(trifluoromethyl)pyridin-2-yl)oxy)benzamido)pent-4-ynoate; (S)-3-(3-((4-(Aminomethyl)-6-(trifluoromethyl)pyridin-2-yl)oxy)benzamido)pent-4-ynoic acid; Methyl(R)-3-(3-((4-(aminomethyl)-6-(trifluoromethyl)pyridin-2-yl)oxy)benzamido)pent-4-ynoate; (R)-3-(3-((4-(Aminomethyl)-6-(trifluoromethyl)pyridin-2-yl)oxy)benzamido)pent-4-ynoic acid; 3-((4-(Aminomethyl)-6-(trifluoromethyl)pyridin-2-yl)oxy)benzoic acid; 3-((4-(Aminomethyl)-6-(trifluoromethyl)pyridin-2-yl)oxy)-N-(2-aminophenyl)benzamide; 3-((4-(Aminomethyl)-6-(trifluoromethyl)pyridin-2-yl)oxy)-N-(pyrimidin-5-yl)benzamide; 3-((4-(Aminomethyl)-6-(trifluoromethyl)pyridin-2-yl)oxy)-N-(oxazol-2-yl)benzamide; 3-((4-(Aminomethyl)-6-(trifluoromethyl)pyridin-2-yl)oxy)-N-(1,3,4-oxadiazol-2-yl)benzamide; Racemic-trans-(3-((4-(aminomethyl)-6-(trifluoromethyl)pyridin-2-yl)oxy)-4-hydroxyphenyl)(3-fluoro-4-hydroxypyrrolidin-1-yl)methanone; Racemic-trans-(3-((4-(aminomethyl)-6-(trifluoromethyl)pyridin-2-yl)oxy)-5-hydroxyphenyl)(3-fluoro-4-hydroxypyrrolidin-1-yl)methanone; Racemic-trans-(3-((4-(aminomethyl)-6-(trifluoromethyl)pyridin-2-yl)oxy)-4-(benzyloxy)phenyl)(3-fluoro-4-hydroxypyrrolidin-1-yl)methanone; Racemic-trans-(3-((4-(aminomethyl)-6-(trifluoromethyl)pyridin-2-yl)oxy)-5-methoxyphenyl)(3-fluoro-4-hydroxypyrrolidin-1-yl)methanone; (S)-(3-(((4-(Aminomethyl)-6-(trifluoromethyl)pyridin-2-yl)amino)methyl)phenyl)(3-hydroxypyrrolidin-1-yl)methanone; Methyl 3-((4-(aminomethyl)-6-(trifluoromethyl)pyridin-2-yl)carbamoyl)benzoate; 3-((4-(Aminomethyl)-6-(trifluoromethyl)pyridin-2-yl)carbamoyl)benzoic acid; N1-(4-(Aminomethyl)-6-(trifluoromethyl)pyridin-2-yl)-N3-phenylisophthalamide; (S)-N-(4-(Aminomethyl)-6-(trifluoromethyl)pyridin-2-yl)-3-(3-hydroxypyrrolidine-1-carbonyl)benzamide; N1-(4-(Aminomethyl)-6-(trifluoromethyl)pyridin-2-yl)-N3-(2-(methylsulfonyl)ethyl)isophthalamide; 3-((4-(Aminomethyl)-6-(trifluoromethyl)pyridin-2-yl)oxy)-N-(3-ethylphenyl)benzamide; 3-((4-(Aminomethyl)-6-(trifluoromethyl)pyridin-2-yl)oxy)-N-(4-ethylphenyl)benzamide; 3-((4-(Aminomethyl)-6-(trifluoromethyl)pyridin-2-yl)oxy)-N-(3-ethynylphenyl)benzamide; 3-((4-(Aminomethyl)-6-(trifluoromethyl)pyridin-2-yl)oxy)-N-(prop-2-yn-1-yl)benzamide; 3-((4-(Aminomethyl)-6-(trifluoromethyl)pyridin-2-yl)oxy)-N-(4-methyl-2-oxo-2H -chromen-7-yl)benzamide; (R,S)-cis-(3-((4-(Aminomethyl)-6-(trifluoromethyl)pyridin-2-yl)oxy)phenyl)(3-fluoro-4-hydroxypyrrolidin-1-yl)methanone; (S,R)-cis-(3-((4-(Aminomethyl)-6-(trifluoromethyl)pyridin-2-yl)oxy)phenyl)(3-fluoro-4-hydroxypyrrolidin-1-yl)methanone; or a pharmaceutically acceptable salt thereof.
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- 19. A compound that has the following structure:
- 21. A compound that has the following structure:
- 23. A compound that is trans-(3-((4-(aminomethyl)-6-(trifluoromethyl)pyridin-2-yl)oxy)phenyl)(3-fluoro-4-hydroxypyrrolidin-1-yl)methanone, or a pharmaceutically acceptable salt thereof.
Specification