Heterocyclic compounds useful as Pim kinase inhibitors

Patent metadata

Field	Value
Publication number	US-11053215-B2
Application number	US-201916564229-A
Country	US
Kind code	B2
Filing date	Sep 9, 2019
Priority date	Oct 2, 2015
Publication date	Jul 6, 2021
Grant date	Jul 6, 2021

Abstract

The present application is concerned with heterocyclic compounds that inhibit the activity of Pim kinases and are useful in the treatment of diseases related to the activity of Pim kinases including, e.g., cancers and other diseases.

First claim

What is claimed is:

1. A method of treating a myeloproliferative disorder, comprising administering to a patient in need thereof a therapeutically effective amount of a compound selected from:
N-{4-[(1R,3S,5S)-3-Amino-5-methylcyclohexyl]pyridin-3-yl}-5-fluoroquinoline-8-carboxamide;
N-{4-[(1R,3S,5S)-3-Amino-5-methylcyclohexyl]pyridin-3-yl}-5-fluoro-3-[(3R)-3-fluoropiperidin-1-yl]quinoline-8-carboxamide;
N-{4-[(1R,3S,5S)-3-Amino-5-methylcyclohexyl]pyridin-3-yl}-5-fluoro-3-pyrrolidin-1-ylquinoline-8-carboxamide;
N-{4-[(1R,3S,5S)-3-Amino-5-methylcyclohexyl]pyridin-3-yl}-3-azetidin-1-yl-5-fluoroquinoline-8-carboxamide;
N-{4-[(1R,3S,5S)-3-Amino-5-methylcyclohexyl]pyridin-3-yl}-5-fluoro-3-[(3S)-3-fluoropyrrolidin-1-yl]quinoline-8-carboxamide;
N-{4-[(1R,3S,5S)-3-Amino-5-methylcyclohexyl]pyridin-3-yl}-5-fluoro-3-[(3R)-3-fluoropyrrolidin-1-yl]quinoline-8-carboxamide;
N-{4-[(1R,3S,5S)-3-Amino-5-methylcyclohexyl]pyridin-3-yl}-3-[(3S)-3-cyanopyrrolidin-1-yl]-5-fluoroquinoline-8-carboxamide;
N-{4-[(1R,3S,5S)-3-Amino-5-methylcyclohexyl]pyridin-3-yl}-3-[(3R)-3-cyanopyrrolidin-1-yl]-5-fluoroquinoline-8-carboxamide;
N-{4-[(1R,3S,5S)-3-Amino-5-methylcyclohexyl]pyridin-3-yl}-5-fluoro-3-(3-fluoroazetidin-1-yl)quinoline-8-carboxamide;
N-{4-[(1R,3S,5S)-3-Amino-5-methylcyclohexyl]pyridin-3-yl}-5-fluoro-3-morpholin-4-ylquinoline-8-carboxamide;
N-{4-[(1R,3S,5S)-3-Amino-5-methylcyclohexyl]pyridin-3-yl}-5-fluoro-3-[(3S)-3-methoxypiperidin-1-yl]quinoline-8-carboxamide;
N-{4-[(1R,3S,5S)-3-Amino-5-methylcyclohexyl]pyridin-3-yl}-5-fluoro-3-[(3S)-3-methoxypiperidin-1-yl]quinoline-8-carboxamide;
N-{4-[(1R,3S,5S)-3-Amino-5-methylcyclohexyl]pyridin-3-yl}-3-cyclopropyl-5-fluoroquinoline-8-carboxamide;
N-{4-[(1R,3S,5S)-3-Amino-5-methylcyclohexyl]pyridin-3-yl}-3-(cyclopropylethynyl)-5-fluoroquinoline-8-carboxamide;
N-{4-[(1R,3S,5S)-3-Amino-5-methylcyclohexyl]pyridin-3-yl}-3-(2-cyano-6-fluorophenyl)-5-fluoroquinoline-8-carboxamide;
tert-Butyl {(1S,3R,5S)-3-[3-({[3-(2,6-difluorophenyl)-5-fluoroquinolin-8-yl]carbonyl}amino)pyridin-4-yl]-5-methylcyclohexyl}carbamate;
N-{4-[(1R,3S,5S)-3-Amino-methylcyclohexyl]pyridin-3-yl}-3-(2-cyanophenyl)-5-fluoroquinoline-8-carboxamide;
N-{4-[(1R,3S,5S)-3-Amino-methylcyclohexyl]pyridin-3-yl}-3-(2,6-difluoro-4-hydroxyphenyl)-5-fluoroquinoline-8-carboxamide;
N-{4-[(1R,3S,5S)-3-Amino-5-methylcyclohexyl]pyridin-3-yl}-3-[cyclopropylmethyl)(methyl)amino]-5-fluoroquinoline-8-carboxamide;
N-(4-((1R,3S,5S)-3-Amino-5-methylcyclohexyl)pyridin-3-yl)-3-(ethyl(methyl)amino)-5-fluoroquinoline-8-carboxamide;
N-{4-[(1R,3S,5S)-3-Amino-5-methylcyclohexyl]pyridin-3-yl}-5-fluoro-3-[methyl(2,2,2-trifluoroethyl)amino]quinoline-8-carboxamide;
N-{4-[(1R,3S,5S)-3-Amino-5-methylcyclohexyl]pyridin-3-yl}-5-fluoro-3-[(2-fluoroethyl)(methyl)amino]quinoline-8-carboxamide;
N-{4-[(1R,3S,5S)-3-Amino-5-methylcyclohexyl]pyridin-3-yl}-5-fluoro-3-[methyl(tetrahydrofuran-3-yl)amino]quinoline-8-carboxamide;
N-{4-[(1R,3S,5S)-3-Amino-5-methylcyclohexyl]pyridin-3-yl}-3-[cyclobutyl(methyl)amino]-5-fluoroquinoline-8-carboxamide;
N-{4-[(1R,3S,5S)-3-Amino-5-methylcyclohexyl]pyridin-3-yl}-3-(dimethylamino)-5-fluoroquinoline-8-carboxamide;
N-{4-[(1R,3S,5S)-3-Amino-5-methylcyclohexyl]pyridin-3-yl}-5-fluoro-3-[(2-fluoroethyl)amino]quinoline-8-carboxamide;
N-{4-[(1R,3S,5S)-3-Amino-5-methylcyclohexyl]pyridin-3-yl}-3-[(2,2-difluoroethyl)amino]-5-fluoroquinoline-8-carboxamide;
N-{4-[(1R,3S,5S)-3-Amino-5-methylcyclohexyl]pyridin-3-yl}-3-(3,3-difluoropiperidin-1-yl)-5-fluoroquinoline-8-carboxamide;
N-{4-[(1R,3S,5S)-3-Amino-5-methylcyclohexyl]pyridin-3-yl}-5-fluoro-3-[(3S,4S)-3-fluoro-4-hydroxypiperidin-1-yl]quinoline-8-carboxamide;
N-{4-[(1R,3S,5S)-3-Amino-5-methylcyclohexyl]pyridin-3-yl}-5-fluoro-3-(4-methylpiperazin-1-yl)quinoline-8-carboxamide;
N-{4-[(1R,3S,5S)-3-Amino-5-methylcyclohexyl]pyridin-3-yl}-5-fluoro-3-(tetrahydro-2H-pyran-4-yl)quinoline-8-carboxamide;
N-{4-[(1R,3S,5S)-3-Amino-5-methylcyclohexyl]pyridin-3-yl}-5-fluoro-3-((R)-3-methylmorpholino)quinoline-8-carboxamide;
N-(4-((1R,3S,5S)-3-Amino-5-methylcyclohexyl)pyridin-3-yl)-5-fluoro-3-((S)-3-methylmorpholino)quinoline-8-carboxamide;
N-(4-((1R,3S,5S)-3-Amino-5-methylcyclohexyl)pyridin-3-yl)-5-fluoro-3-((R)-2-methylpyrrolidin-1-yl)quinoline-8-carboxamide;
N-(4-((1R,3S,5S)-3-Amino-5-methylcyclohexyl)pyridin-3-yl)-3-(2,5-dimethylmorpholino)-5-fluoroquinoline-8-carboxamide;
N-(4-((1R,3S,5S)-3-Amino-5-methylcyclohexyl)pyridin-3-yl)-3-(2,5-dimethylpyrrolidin-1-yl)-5-fluoroquinoline-8-carboxamide;
N-(4-((1R,3S,5S)-3-Amino-5-methylcyclohexyl)pyridin-3-yl)-3-(2,6-dimethylmorpholino)-5-fluoroquinoline-8-carboxamide;
N-(4-((1R,3S,5S)-3-Amino-5-methylcyclohexyl)pyridin-3-yl)-5-fluoro-3-((S)-2-methylmorpholino)quinoline-8-carboxamide;
N-(4-((1R,3S,5S)-3-Amino-5-methylcyclohexyl)pyridin-3-yl)-5-fluoro-3-((S)-2-methylpyrrolidin-1-yl)quinoline-8-carboxamide;
N-(4-((1R,3S,5S)-3-Amino-5-methylcyclohexyl)pyridin-3-yl)-3-(4,4-difluoropiperidin-1-yl)-5-fluoroquinoline-8-carboxamide;
N-(4-((1R,3S,5S)-3-Amino-5-methylcyclohexyl)pyridin-3-yl)-5-fluoro-3-(4-hydroxy-4-methylpiperidin-1-yl)quinoline-8-carboxamide;
N-(4-((1R,3S,5S)-3-Amino-5-methylcyclohexyl)pyridin-3-yl)-3-((2,2-difluoroethyl)(methyl)amino)-5-fluoroquinoline-8-carboxamide;
N-(4-((1R,3S,5S)-3-Amino-5-methylcyclohexyl)pyridin-3-yl)-5-fluoro-3-(2-methylpiperidin-1-yl)quinoline-8-carboxamide;
N-(4-((1R,3S,5S)-3-Amino-5-methylcyclohexyl)pyridin-3-yl)-5-fluoro-3-(4-hydroxypiperidin-1-yl)quinoline-8-carboxamide;
N-(4-((1R,3S,5S)-3-Amino-5-methylcyclohexyl)pyridin-3-yl)-3-(4-cyanopiperidin-1-yl)-5-fluoroquinoline-8-carboxamide;
N-(4-((1R,3S,5S)-3-Amino-5-methylcyclohexyl)pyridin-3-yl)-5-fluoro-3-(4-methylpiperidin-1-yl)quinoline-8-carboxamide;
N-(4-((1R,3S,5S)-3-Amino-5-methylcyclohexyl)pyridin-3-yl)-5-fluoro-3-((R)-2-(methoxymethyl)pyrrolidin-1-yl)quinoline-8-carboxamide;
N-(4-((1R,3S,5S)-3-Amino-5-methylcyclohexyl)pyridin-3-yl)-5-fluoro-3-((S)-2-(methoxymethyl)pyrrolidin-1-yl)quinoline-8-carboxamide;
N-(4-((1R,3S,5S)-3-Amino-5-methylcyclohexyl)pyridin-3-yl)-5-fluoro-3-((R)-3-methoxypyrrolidin-1-yl)quinoline-8-carboxamide;
N-(4-((1R,3S,5S)-3-Amino-5-methylcyclohexyl)pyridin-3-yl)-5-fluoro-3-((S)-3-methoxypyrrolidin-1-yl)quinoline-8-carboxamide;
N-(4-((1R,3S,5S)-3-Amino-5-methylcyclohexyl)pyridin-3-yl)-5-fluoro-3-((2-methoxymethyl)(methyl)amino)quinoline-8-carboxamide;
N-(4-((1R,3S,5S)-3-Amino-5-methylcyclohexyl)pyridin-3-yl)-3-((S)-1-cyclopropylethylamino)-5-fluoroquinoline-8-carboxamide;
N-(4-((1R,3S,5S)-3-Amino-5-methylcyclohexyl)pyridin-3-yl)-5-fluoro-3-((S)-3-methylbutan-2-ylamino)quinoline-8-carboxamide;
N-(4-((1R,3S,5S)-3-amino-5-methylcyclohexyl)pyridin-3-yl)-5-fluoro-3-((R)-3-methylbutan-2-ylamino)quinoline-8-carboxamide;
N-(4-((1R,3S,5S)-3-Amino-5-methylcyclohexyl)pyridin-3-yl)-5-fluoro-3-(methyl(propyl)amino)quinoline-8-carboxamide;
N-(4-((1R,3S,5S)-3-Amino-5-methylcyclohexyl)pyridin-3-yl)-5-fluoro-3-isopropyl(methyl)amino)quinoline-8-carboxamide;
N-(4-((1R,3S,5S)-3-Amino-5-methylcyclohexyl)pyridin-3-yl)-3-(2-ethylpiperidin-1-yl)-5-fluoroquinoline-8-carboxamide;
N-(4-((1R,3S,5S)-3-Amino-5-methylcyclohexyl)pyridin-3-yl)-3-(2-(difluoromethyl)piperidin-1-yl)-5-fluoroquinoline-8-carboxamide;
N-(4-((1R,3S,5S)-3-Amino-5-methylcyclohexyl)pyridin-3-yl)-5,6′-difluoro-3,8′-biquinoline-8-carboxamide;
N-(4-((1R,3S,5S)-3-Amino-5-methylcyclohexyl)pyridin-3-yl)-5,5′-difluoro-3,8′-biquinoline-8-carboxamide;
N-(4-((1R,3S,5S)-3-Amino-5-methylcyclohexyl)pyridin-3-yl)-5-fluoro-3-(6-(trifluoromethyl)pyridin-3-yl)quinoline-8-carboxamide;
N-(4-((1R,3S,5S)-3-Amino-5-methylcyclohexyl)pyridin-3-yl)-3-(1-ethyl-1H-pyrazol-4-yl)-5-fluoroquinoline-8-carboxamide;
N-(4-((1R,3S,5S)-3-Amino-5-methylcyclohexyl)pyridin-3-yl)-3-(1,3-dimethyl-1H-pyrazol-4-yl)-5-fluoroquinoline-8-carboxamide;
N-(4-((1R,3S,5S)-3-Amino-5-methylcyclohexyl)pyridin-3-yl)-5-fluoro-3-(1-methyl-1H-pyrazol-4-yl)quinoline-8-carboxa

Assignees

• Incyte Corp

Inventors

• Vechorkin Oleg
• Li Yun-Long
• Sokolsky Alexander
• Wang Anlai
• Zhu Wenyu
• Zhuo Jincong

Classifications

• C07D487/04

  Ortho-condensed systems · CPC title

• C07D417/14

  containing three or more hetero rings · CPC title

• C07D401/14

  containing three or more hetero rings · CPC title

• C07D401/12 Primary

  linked by a chain containing hetero atoms as chain links · CPC title

• C07D413/14

  containing three or more hetero rings · CPC title