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US 2022/0089568 A1Published application
Dihydroorotate dehydrogenase inhibitors
AssigneeJanssen Biotech, Inc.
InventorsJustin Cisar, Scott Kuduk, Chao-yuan Wang, Yvan Rene Ferdinand Simonnet, Colleen Elizabeth Keohane, Edgar Jacoby
Life of this patent
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Abstract
Disclosed are compounds, compositions and methods for treating diseases, disorders, or medical conditions that are affected by the modulation of DHODH. Such compounds are represented by Formula (I) as follows: wherein R1a, R1b, R2, and R3, are defined herein.
Claims39
A compound having the structure of Formula (I):
- wherein
- X is selected from the group consisting of:
- O, S and NRa;
- when X is NRa;
- Ra is H or CH3;
- or Ra and R1a come together to form a heterocyclic ring selected from the group consisting of:
- wherein the heterocyclic ring is substituted with one or two members each independently selected from the group consisting of:
- C1-6alkyl, C1-6haloalkyl, and OC1-6alkyl;
- R1a is selected from the group consisting of:
- C1-6alkyl;
- C1-6alkyl substituted with OH, or OCH3;
- C1-6haloalkyl;
- C1-6haloalkyl substituted with OH, or OCH3;
- and C3-6cycloalkyl;
- R1b is CH3 or CHF2;
- or R1a and R1b come together to form C3-6cycloalkyl;
- C3-6cycloalkyl independently substituted with one, two, three or four members each independently selected from the group consisting of:
- halo, OH, C1-6alkyl, and C1-6haloalkyl;
- oxetanyl;
- tetrahydrofuranyl;
- and tetrahydropyranyl;
- R2 is
- where
- Rb is C1-6alkyl substituted with a member selected from the group consisting of:
- OH, halo, CN, OC1-6alkyl, OC1-6haloalkyl and OC3-6cycloalkyl;
- Rc is selected from the group consisting of:
- C1-6alkyl, C1-6alkyl substituted with OH, allyl, C1-6haloalkyl, and C3-6cycloalkyl;
- and
- R3 is selected from the group consisting of:
- Rd is selected from the group consisting of:
- H;
- halo;
- C1-6alkyl;
- C1-6alkyl substituted with a member selected from the group consisting of:
- OH, OCH3, SCH3, and OCF3;
- C1-6haloalkyl;
- C1-6haloalkyl substituted with a member selected from the group consisting of:
- OH, and OCH3;
- N(CH3)2;
- OH;
- CN and OC1-6alkyl;
- Re is selected from the group consisting of:
- halo;
- C1-6alkyl;
- C1-6alkyl substituted with a member selected from the group consisting of:
- OH, OCH3, SCH3, and OCF3;
- C1-6haloalkyl;
- C1-6haloalkyl substituted with a member selected from the group consisting of:
- OH, and OCH3;
- OH;
- OC1-6alkyl;
- and C3-6cycloalkyl;
- Rf is selected from the group consisting of:
- H;
- C1-6alkyl;
- C1-6alkyl substituted with a member selected from the group consisting of:
- OH, OCH3, SCH3, and OCF3;
- C1-6haloalkyl;
- and C1-6haloalkyl substituted with a member selected from the group consisting of:
- OH, and OCH3;
- and
- n is 1, or 2;
- or a pharmaceutically acceptable salt, solvate, stereoisomer, tautomer, isotopic variant, or N-oxide thereof.
60 more elements
A compound selected from the group consisting of:
- (S)-N-(2-Chloro-6-fluorophenyl)-6-(4-ethyl-3-(hydroxymethyl)-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl)-5-fluoro-2-((1,1,1-trifluoropropan-2-yl)oxy)nicotinamide;
- (S)-6-(4-Ethyl-3-(hydroxymethyl)-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl)-5-fluoro-N-(2-fluorophenyl)-2-((1,1,1-trifluoropropan-2-yl)oxy)nicotinamide;
- (S)-N-(2-Chloro-6-fluorophenyl)-6-(4-ethyl-3-(fluoromethyl)-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl)-5-fluoro-2-((1,1,1-trifluoropropan-2-yl)oxy)nicotinamide;
- (S)-N-(2-Chloropyridin-3-yl)-6-(4-ethyl-3-(hydroxymethyl)-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl)-5-fluoro-2-((1,1,1-trifluoropropan-2-yl)oxy)nicotinamide;
- (S)-N-(2-Chloro-4-methylpyridin-3-yl)-6-(4-ethyl-3-(hydroxymethyl)-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl)-5-fluoro-2-((1,1,1-trifluoropropan-2-yl)oxy)nicotinamide;
- (S)-N-(2-Chloro-6-fluorophenyl)-6-(3-(chloromethyl)-4-ethyl-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl)-5-fluoro-2-((1,1,1-trifluoropropan-2-yl)oxy)nicotinamide;
- N-(2-Chloro-6-fluorophenyl)-6-(4-ethyl-3-(hydroxymethyl)-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl)-5-fluoro-2-isopropoxynicotinamide;
- N-(2-Chloro-6-fluorophenyl)-6-(4-ethyl-3-(hydroxymethyl)-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl)-5-fluoro-2-(2,2,3,3 -tetrafluorocyclobutoxy)nicotinamide;
- Racemic-N-(2-Chloro-6-fluorophenyl)-6-(4-ethyl-3-(hydroxymethyl)-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl)-5-fluoro-2-((tetrahydrofuran-3-yl)oxy)nicotinamide;
- (S)-N-(3-Chloropyridin-4-yl)-6-(4-ethyl-3-(hydroxymethyl)-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl)-5-fluoro-2-((1,1,1-trifluoropropan-2-yl)oxy)nicotinamide;
- (S)-6-(4-Ethyl-3-(hydroxymethyl)-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl)-5-fluoro-N-(2-fluoro-5-methylphenyl)-2-((1,1,1-trifluoropropan-2-yl)oxy)nicotinamide;
- (S)-6-(4-Ethyl-3-(hydroxymethyl)-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl)-5-fluoro-N-(isothiazol-4-yl)-2-((1,1,1-trifluoropropan-2-yl)oxy)nicotinamide;
- (S)-N-(2-(Difluoromethyl)-4-methylpyridin-3-yl)-6-(4-ethyl-3-(hydroxymethyl)-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl)-5-fluoro-2-((1,1,1-trifluoropropan-2-yl)oxy)nicotinamide;
- (S)-N-(2-Chloro-6-fluorophenyl)-6-(4-ethyl-3-(methoxymethyl)-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl)-5-fluoro-2-((1,1,1-trifluoropropan-2-yl)oxy)nicotinamide;
- (S)-N-(5-Bromoisothiazol-4-yl)-6-(4-ethyl-3-(hydroxymethyl)-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl)-5-fluoro-2-((1,1,1-trifluoropropan-2-yl)oxy)nicotinamide;
- (S)-N-(3-Chloropyridazin-4-yl)-6-(4-ethyl-3-(hydroxymethyl)-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl)-5-fluoro-2-((1,1,1-trifluoropropan-2-yl)oxy)nicotinamide;
- (S)-6-(4-Ethyl-3-(hydroxymethyl)-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl)-5-fluoro-N-(3-methylisothiazol-4-yl)-2-((1,1,1-trifluoropropan-2-yl)oxy)nicotinamide;
- (S)-N-(2,4-Dimethylpyridin-3-yl)-6-(4-ethyl-3-(hydroxymethyl)-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl)-5-fluoro-2-((1,1,1-trifluoropropan-2-yl)oxy)nicotinamide;
- (S)-N-(3-Chloropyrazin-2-yl)-6-(4-ethyl-3-(hydroxymethyl)-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl)-5-fluoro-2-((1,1,1-trifluoropropan-2-yl)oxy)nicotinamide;
- (S)-N-(3-Chloro-2-oxo-1,2-dihydropyridin-4-yl)-6-(4-ethyl-3-(hydroxymethyl)-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl)-5-fluoro-2-((1,1,1-trifluoropropan-2-yl)oxy)nicotinamide;
- (S)-N-(3-chloro-6-methoxypyridin-2-yl)-6-(4-ethyl-3-(hydroxymethyl)-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl)-5-fluoro-2-((1,1,1-trifluoropropan-2-yl)oxy)nicotinamide;
- (S)-N-(3,5-Dichloro-2-oxo-1,2-dihydropyridin-4-yl)-6-(4-ethyl-3-(hydroxymethyl)-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl)-5-fluoro-2-((1,1,1-trifluoropropan-2-yl)oxy)nicotinamide;
- (S)-N-(3-chloro-6-oxo-1,6-dihydropyridin-2-yl)-6-(4-ethyl-3-(hydroxymethyl)-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl)-5-fluoro-2-((1,1,1-trifluoropropan-2-yl)oxy)nicotinamide;
- (S)-N-(3-Chloro-2-methoxypyridin-4-yl)-6-(4-ethyl-3-(hydroxymethyl)-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl)-5-fluoro-2-((1,1,1-trifluoropropan-2-yl)oxy)nicotinamide;
- (S)-N-(5-Chloro-3-methyl-1H-pyrazol-4-yl)-6-(4-ethyl-3-(hydroxymethyl)-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl)-5-fluoro-2-((1,1,1-trifluoropropan-2-yl)oxy)nicotinamide;
- (S)-N-(4-Chloro-3-methylisothiazol-5-yl)-6-(4-ethyl-3-(hydroxymethyl)-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl)-5-fluoro-2-((1,1,1-trifluoropropan-2-yl)oxy)nicotinamide;
- (S)-N-(4-Chloropyridin-3-yl)-6-(4-ethyl-3-(hydroxymethyl)-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl)-5-fluoro-2-((1,1,1-trifluoropropan-2-yl)oxy)nicotinamide;
- (S)-N-(3-Chloro-5-fluoropyridin-4-yl)-6-(4-ethyl-3-(hydroxymethyl)-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl)-5-fluoro-2-((1,1,1-trifluoropropan-2-yl)oxy)nicotinamide;
- (S)-N-(3-Cyano-5-fluoropyridin-4-yl)-6-(4-ethyl-3-(hydroxymethyl)-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl)-5-fluoro-2-((1,1,1-trifluoropropan-2-yl)oxy)nicotinamide;
- (S)-N-(3-Chloro-5-fluoro-2-methoxypyridin-4-yl)-6-(4-ethyl-3-(hydroxymethyl)-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl)-5-fluoro-2-((1,1,1-trifluoropropan-2-yl)oxy)nicotinamide;
- (S)-N-(4-Bromo-3-methylisothiazol-5-yl)-6-(4-ethyl-3-(hydroxymethyl)-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl)-5-fluoro-2-((1,1,1-trifluoropropan-2-yl)oxy)nicotinamide;
- (S)-6-(4-Ethyl-3-(hydroxymethyl)-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl)-5-fluoro-N-(5-methylthiazol-4-yl)-2-((1,1,1-trifluoropropan-2-yl)oxy)nicotinamide;
- (S)-N-(5-Chloro-2-methoxypyridin-3-yl)-6-(4-ethyl-3-(hydroxymethyl)-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl)-5-fluoro-2-((1,1,1-trifluoropropan-2-yl)oxy)nicotinamide;
- (S)-6-(4-Ethyl-3-(hydroxymethyl)-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl)-5-fluoro-N-(3-methoxypyrazin-2-yl)-2-((1,1,1-trifluoropropan-2-yl)oxy)nicotinamide;
- (S)-N-(3,5-Dimethylisothiazol-4-yl)-6-(4-ethyl-3-(hydroxymethyl)-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl)-5-fluoro-2-((1,1,1-trifluoropropan-2-yl)oxy)nicotinamide;
- (S)-6-(4-Ethyl-3-(hydroxymethyl)-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl)-5-fluoro-N-(2-fluoro-5-methylpyridin-3-yl)-2-((1,1,1-trifluoropropan-2-yl)oxy)nicotinamide;
- (S)-6-(4-Ethyl-3-(hydroxymethyl)-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl)-5-fluoro-N-(5-fluoro-2-methylpyridin-4-yl)-2-((1,1,1-trifluoropropan-2-yl)oxy)nicotinamide;
- (S)-N-(4-Chloro-6-methylpyrimidin-5-yl)-6-(4-ethyl-3-(hydroxymethyl)-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl)-5-fluoro-2-((1,1,1-trifluoropropan-2-yl)oxy)nicotinamide;
- (S)-6-(4-Ethyl-3-(hydroxymethyl)-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl)-5-fluoro-N-(3-fluoro-6-methylpyridin-2-yl)-2-((1,1,1-trifluoropropan-2-yl)oxy)nicotinamide;
- (S)-N-(3-Chloro-2-methoxy-5-methylpyridin-4-yl)-6-(4-ethyl-3-(hydroxymethyl)-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl)-5-fluoro-2-((1,1,1-trifluoropropan-2-yl)oxy)nicotinamide;
- (S)-6-(4-Ethyl-3-(hydroxymethyl)-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl)-5-fluoro-N-(2-methoxy-5-methylpyridin-3-yl)-2-((1,1,1-trifluoropropan-2-yl)oxy)nicotinamide;
- (S)-6-(4-Ethyl-3-(hydroxymethyl)-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl)-5-fluoro-N-(2-fluoro-4-methylpyridin-3-yl)-2-((1,1,1-trifluoropropan-2-yl)oxy)nicotinamide;
- (S)-N-(5,6-Dimethylpyrimidin-4-yl)-6-(4-ethyl-3-(hydroxymethyl)-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl)-5-fluoro-2-((1,1,1-trifluoropropan-2-yl)oxy)nicotinamide;
- (S)-N-(2-Chloro-4-methoxypyridin-3-yl)-6-(4-ethyl-3-(hydroxymethyl)-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl)-5-fluoro-2-((1,1,1-trifluoropropan-2-yl)oxy)nicotinamide;
- (S)-6-(4-Ethyl-3-(hydroxymethyl)-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl)-5-fluoro-N-(3-methylisoxazol-4-yl)-2-((1,1,1-trifluoropropan-2-yl)oxy)nicotinamide;
- (S)-N-(3,5-Dimethylisoxazol-4-yl)-6-(4-ethyl-3-(hydroxymethyl)-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl)-5-fluoro-2-((1,1,1-trifluoropropan-2-yl)oxy)nicotinamide;
- (S)-6-(4-Ethyl-3-(hydroxymethyl)-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl)-5-fluoro-N-(2-fluoro-5-methoxyphenyl)-2-((1,1,1-trifluoropropan-2-yl)oxy)nicotinamide;
- (S)-N-(2-Chloro-5-methylphenyl)-6-(4-ethyl-3-(hydroxymethyl)-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl)-5-fluoro-2-((1,1,1-trifluoropropan-2-yl)oxy)nicotinamide;
- (S)-N-(3,5-Dimethyl-1H-pyrazol-4-yl)-6-(4-ethyl-3-(hydroxymethyl)-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl)-5-fluoro-2-((1,1,1-trifluoropropan-2-yl)oxy)nicotinamide;
- (S)-N-(4-Chloro-6-methoxypyridin-3-yl)-6-(4-ethyl-3-(hydroxymethyl)-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl)-5-fluoro-2-((1,1,1-trifluoropropan-2-yl)oxy)nicotinamide;
- (S)-N-(2,5-Dimethylpyridin-3-yl)-6-(4-ethyl-3-(hydroxymethyl)-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl)-5-fluoro-2-((1,1,1-trifluoropropan-2-yl)oxy)nicotinamide;
- (S)-N-(5-Chloro-2-methoxypyridin-3-yl)-6-(4-ethyl-3-(hydroxymethyl)-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl)-5-fluoro-2-((1,1,1-trifluoropropan-2-yl)oxy)nicotinamide;
- N-(1,4-Dimethyl-2-oxo-2,3-dihydro-1l4-pyridin-3-yl)-6-(4-ethyl-3-(hydroxymethyl)-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl)-5-fluoro-2-(((S)-1,1,1-trifluoropropan-2-yl)oxy)nicotinamide;
- (S)-N-(3-Chloropyridin-2-yl)-6-(4-ethyl-3-(hydroxymethyl)-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl)-5-fluoro-2-((1,1,1-trifluoropropan-2-yl)oxy)nicotinamide;
- (S)-6-(4-Ethyl-3-(hydroxymethyl)-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl)-5-fluoro-2-((1,1,1-trifluoropropan-2-yl)oxy)-N-(1,3,5-trimethyl-1H-pyrazol-4-yl)nicotinamide;
- (S)-6-(4-Ethyl-3-(hydroxymethyl)-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl)-5-fluoro-N-(3-fluoro-6-methoxypyridin-2-yl)-2-((1,1,1-trifluoropropan-2-yl)oxy)nicotinamide;
- (S)-6-(4-Ethyl-3-(hydroxymethyl)-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl)-5-fluoro-N-(3-methyl-1H-pyrazol-4-yl)-2-((1,1,1-trifluoropropan-2-yl)oxy)nicotinamide;
- (S)-6-(4-Ethyl-3-(hydroxymethyl)-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl)-5-fluoro-N-(3-methoxy-1H-pyrazol-4-yl)-2-((1,1,1-trifluoropropan-2-yl)oxy)nicotinamide;
- (S)-6-(4-Ethyl-3-(hydroxymethyl)-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl)-5-fluoro-N-(3-isopropyl-1-methyl-1H-pyrazol-5-yl)-2-((1,1,1-trifluoropropan-2-yl)oxy)nicotinamide;
- (S)-N-(5-Chloro-6-methylpyrimidin-4-yl)-6-(4-ethyl-3-(hydroxymethyl)-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl)-5-fluoro-2-((1,1,1-trifluoropropan-2-yl)oxy)nicotinamide;
- (S)-6-(4-Ethyl-3-(hydroxymethyl)-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl)-5-fluoro-N-(3-(methoxymethyl)-1-methyl-1H-pyrazol-4-yl)-2-((1,1,1-trifluoropropan-2-yl)oxy)nicotinamide;
- (S)-N-(3-Cyclopropyl-1H-pyrazol-4-yl)-6-(4-ethyl-3-(hydroxymethyl)-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl)-5-fluoro-2-((1,1,1-trifluoropropan-2-yl)oxy)nicotinamide;
- (S)-6-(4-Ethyl-3-(hydroxymethyl)-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl)-5-fluoro-N-(1-(2-methoxyethyl)-1H-pyrazol-4-yl)-2-((1,1,1-trifluoropropan-2-yl)oxy)nicotinamide;
- (S)-N-(3-Chloro-1-methyl-6-oxo-1,6-dihydropyridin-2-yl)-6-(4-ethyl-3-(hydroxymethyl)-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl)-5-fluoro-2-((1,1,1-trifluoropropan-2-yl)oxy)nicotinamide;
- (S)-6-(4-Ethyl-3-(hydroxymethyl)-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl)-5-fluoro-N-(5-fluoro-2-methoxypyridin-4-yl)-2-((1,1,1-trifluoropropan-2-yl)oxy)nicotinamide;
- (S)-6-(4-ethyl-3-(hydroxymethyl)-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl)-5-fluoro-N-(2-methoxy-5-methylpyridin-4-yl)-2-((1,1,1-trifluoropropan-2-yl)oxy)nicotinamide;
- (S)-N-(2-Chloro-5-methylpyridin-3-yl)-6-(4-ethyl-3-(hydroxymethyl)-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl)-5-fluoro-2-((1,1,1-trifluoropropan-2-yl)oxy)nicotinamide;
- (S)-6-(4-Ethyl-3-(hydroxymethyl)-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl)-5-fluoro-N-(2-methoxy-4-methylpyridin-3-yl)-2-((1,1,1-trifluoropropan-2-yl)oxy)nicotinamide;
- (S)-N-(2,4-Dichloropyridin-3-yl)-6-(4-ethyl-3-(hydroxymethyl)-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl)-5-fluoro-2-((1,1,1-trifluoropropan-2-yl)oxy)nicotinamide;
- (S)-N-(2-Ethoxy-5-fluoropyrimidin-4-yl)-6-(4-ethyl-3-(hydroxymethyl)-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl)-5-fluoro-2-((1,1,1-trifluoropropan-2-yl)oxy)nicotinamide;
- (S)-6-(4-Ethyl-3-(hydroxymethyl)-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl)-5-fluoro-N-(3-fluoro-5-methylpyridin-4-yl)-2-((1,1,1-trifluoropropan-2-yl)oxy)nicotinamide;
- (S)-N-(2-Chloro-4,6-dimethylpyridin-3-yl)-6-(4-ethyl-3-(hydroxymethyl)-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl)-5-fluoro-2-((1,1,1-trifluoropropan-2-yl)oxy)nicotinamide;
- (S)-N-(1-Cyclopropyl-1H-imidazol-2-yl)-6-(4-ethyl-3-(hydroxymethyl)-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl)-5-fluoro-2-((1,1,1-trifluoropropan-2-yl)oxy)nicotinamide;
- (S)-N-(2-Chloro-5-cyanophenyl)-6-(4-ethyl-3-(hydroxymethyl)-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl)-5-fluoro-2-((1,1,1-trifluoropropan-2-yl)oxy)nicotinamide;
- (S)-N-(2-Chloro-5-cyanopyridin-3-yl)-6-(4-ethyl-3-(hydroxymethyl)-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl)-5-fluoro-2-((1,1,1-trifluoropropan-2-yl)oxy)nicotinamide;
- (S)-N-(4-(Dimethylamino)-2-methoxypyridin-3-yl)-6-(4-ethyl-3-(hydroxymethyl)-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl)-5-fluoro-2-((1,1,1-trifluoropropan-2-yl)oxy)nicotinamide;
- N-(2-Chloro-6-methyl-3-pyridyl)-6-[4-ethyl-3-(hydroxymethyl)-5-oxo-1,2,4-triazol-1-yl]-5-fluoro-2-[(1S)-2,2,2-trifluoro-1-methyl-ethoxy]pyridine-3-carboxamide;
- N-(2-Chloro-5-fluoro-3-pyridyl)-6-[4-ethyl-3-(hydroxymethyl)-5-oxo-1,2,4-triazol-1-yl]-5-fluoro-2-[(1S)-2,2,2-trifluoro-1-methyl-ethoxy]pyridine-3-carboxamide;
- N-(4-Chloro-2-methyl-3-pyridyl)-6-[4-ethyl-3-(hydroxymethyl)-5-oxo-1,2,4-triazol-1-yl]-5-fluoro-2-[(1S)-2,2,2-trifluoro-1-methyl-ethoxy]pyridine-3-carboxamide;
- N-(3-Chloro-1-methyl-pyrazol-4-yl)-6-[4-ethyl-3-(hydroxymethyl)-5-oxo-1,2,4-triazol-1-yl]-5-fluoro-2-[(1S)-2,2,2-trifluoro-1-methyl-ethoxy]pyridine-3-carboxamide;
- N-[2-(Difluoromethyl)-5-fluoro-4-pyridyl]-6-[4-ethyl-3-(hydroxymethyl)-5-oxo-1,2,4-triazol-1-yl]-5-fluoro-2-[(1S)-2,2,2-trifluoro-1-methyl-ethoxy]pyridine-3-carboxamide;
- 6-[4-Ethyl-3-(hydroxymethyl)-5-oxo-1,2,4-triazol-1-yl]-5-fluoro-N-(5-fluoro-2-methoxy-pyrimidin-4-yl)-2-[(1S)-2,2,2-trifluoro-1-methyl-ethoxy]pyridine-3-carboxamide;
- N-(6-Chloro-2,3-dimethyl-phenyl)-6-[4-ethyl-3-(hydroxymethyl)-5-oxo-1,2,4-triazol-1-yl]-5-fluoro-2-[(1S)-2,2,2-trifluoro-1-methyl-ethoxy]pyridine-3-carboxamide;
- N-(2-Chloro-4-methyl-3-pyridyl)-5-fluoro-6-[3-(hydroxymethyl)-5-oxo-4-propyl-1,2,4-triazol-1-yl]-2-[(1S)-2,2,2-trifluoro-1-methyl-ethoxy]pyridine-3-carboxamide;
- 6-[4-Ethyl-3-(hydroxymethyl)-5-oxo-1,2,4-triazol-1-yl]-5-fluoro-N-(2-methoxy-3,5-dimethyl-4-pyridyl)-2-[(1S)-2,2,2-trifluoro-1-methyl-ethoxy]pyridine-3-carboxamide;
- (S)-2-(5-(((2-Chloro-4-methylpyridin-3-yl)-l2-azaneyl)carbonyl)-3-fluoro-6-((1,1,1-trifluoropropan-2-yl)oxy)pyridin-2-yl)-5-(fluoromethyl)-4-isopropyl-2,4-dihydro-3H-1,2,4-triazol-3-one;
- N-(2-Chloro-4-methyl-3-pyridyl)-6-[4-ethyl-3-(fluoromethyl)-5-oxo-1,2,4-triazol-1-yl]-5-fluoro-2-[(1S)-2,2,2-trifluoro-1-methyl-ethoxy]pyridine-3-carboxamide;
- N-(3-Chloro-2-methoxy-5-methyl-4-pyridyl)-6-[4-ethyl-3-(hydroxymethyl)-5-oxo-1,2,4-triazol-1-yl]-5-fluoro-2-isopropoxy-pyridine-3-carboxamide;
- N-(2-Chloro-4-methyl-3-pyridyl)-5-fluoro-6-[3-(hydroxymethyl)-4-isopropyl-5-oxo-1,2,4-triazol-1-yl]-2-[(1S)-2,2,2-trifluoro-1-methyl-ethoxy]pyridine-3-carboxamide;
- N-(2-Chloro-4-methyl-3-pyridyl)-6-[4-(2,2-difluoroethyl)-3-(hydroxymethyl)-5-oxo-1,2,4-triazol-1-yl]-5-fluoro-2-[(1S)-2,2,2-trifluoro-1-methyl-ethoxy]pyridine-3-carboxamide;
- N-(5-Chloro-3-methyl-1H-pyrazol-4-yl)-5-fluoro-6-[3-(hydroxymethyl)-5-oxo-4-propyl-1,2,4-triazol-1-yl]-2-[(1S)-2,2,2-trifluoro-1-methyl-ethoxy]pyridine-3-carboxamide;
- N-(2-Chloro-4-methyl-3-pyridyl)-5-fluoro-6-[3-(fluoromethyl)-5-oxo-4-propyl-1,2,4-triazol-1-yl]-2-[(1S)-2,2,2-trifluoro-1-methyl-ethoxy]pyridine-3-carboxamide;
- N-(2,4-Dimethoxy-3-pyridyl)-6-[4-ethyl-3-(hydroxymethyl)-5-oxo-1,2,4-triazol-1-yl]-5-fluoro-2-[(1S)-2,2,2-trifluoro-1-methyl-ethoxy]pyridine-3-carboxamide;
- N-(4,6-Dimethoxypyrimidin-5-yl)-6-[4-ethyl-3-(hydroxymethyl)-5-oxo-1,2,4-triazol-1-yl]-5-fluoro-2-[(1S)-2,2,2-trifluoro-1-methyl-ethoxy]pyridine-3-carboxamide;
- 6-[4-Ethyl-3-(hydroxymethyl)-5-oxo-1,2,4-triazol-1-yl]-5-fluoro-2-[(1S)-2,2,2-trifluoro-1-methyl-ethoxy]-N-[3-(trifluoromethyl)-1H-pyrazol-4-yl]pyridine-3-carboxamide;
- N-(5-Chloro-3-methyl-1H-pyrazol-4-yl)-6-[4-ethyl-3-(fluoromethyl)-5-oxo-1,2,4-triazol-1-yl]-5-fluoro-2-[(1S)-2,2,2-trifluoro-1-methyl-ethoxy]pyridine-3-carboxamide;
- N-(2-Chloro-4-methyl-3-pyridyl)-6-[4-ethyl-3-(fluoromethyl)-5-oxo-1,2,4-triazol-1-yl]-5-fluoro-2-isopropoxy-pyridine-3-carboxamide;
- N-(5-Chloro-2-methoxy-4-pyridyl)-6-[4-ethyl-3-(hydroxymethyl)-5-oxo-1,2,4-triazol-1-yl]-5-fluoro-2-[(1S)-2,2,2-trifluoro-1-methyl-ethoxy]pyridine-3-carboxamide;
- N-(5-Chloro-3-methyl-1H-pyrazol-4-yl)-5-fluoro-6-[3-(fluoromethyl)-5-oxo-4-propyl-1,2,4-triazol-1-yl]-2-[(1S)-2,2,2-trifluoro-1-methyl-ethoxy]pyridine-3-carboxamide;
- N-(3-Cyano-1H-pyrazol-4-yl)-6-[4-ethyl-3-(hydroxymethyl)-5-oxo-1,2,4-triazol-1-yl]-5-fluoro-2-[(1S)-2,2,2-trifluoro-1-methyl-ethoxy]pyridine-3-carboxamide;
- N-(2-Chloro-4-methyl-3-pyridyl)-5-fluoro-6-[3-(fluoromethyl)-4-(3-hydroxypropyl)-5-oxo-1,2,4-triazol-1-yl]-2-[(1S)-2,2,2-trifluoro-1-methyl-ethoxy]pyridine-3-carboxamide;
- N-(2-chloro-4,5-dimethyl-3-pyridyl)-6-[4-ethyl-3-(hydroxymethyl)-5-oxo-1,2,4-triazol-1-yl]-5-fluoro-2-[(1S)-2,2,2-trifluoro-1-methyl-ethoxy]pyridine-3-carboxamide;
- 6-[4-ethyl-3-(hydroxymethyl)-5-oxo-1,2,4-triazol-1-yl]-5-fluoro-N-(4-methoxy-2,6-dimethyl-3-pyridyl)-2-[(1S)-2,2,2-trifluoro-1-methyl-ethoxy]pyridine-3-carboxamide;
- N-(3-Chloro-4-methoxy-2-pyridyl)-6-[4-ethyl-3-(hydroxymethyl)-5-oxo-1,2,4-triazol-1-yl]-5-fluoro-2-[(1S)-2,2,2-trifluoro-1-methyl-ethoxy]pyridine-3-carboxamide;
- N-(3-Chloro-4-ethoxy-2-pyridyl)-6-[4-ethyl-3-(hydroxymethyl)-5-oxo-1,2,4-triazol-1-yl]-5-fluoro-2-[(1S)-2,2,2-trifluoro-1-methyl-ethoxy]pyridine-3-carboxamide;
- N-(2-Chloro-6-methoxy-4-methyl-3-pyridyl)-6-[4-ethyl-3-(hydroxymethyl)-5-oxo-1,2,4-triazol-1-yl]-5-fluoro-2-[(1S)-2,2,2-trifluoro-1-methyl-ethoxy]pyridine-3-carboxamide;
- N-(3-Chloro-5-methyl-1H-pyrazol-4-yl)-5-fluoro-6-[3-(fluoromethyl)-4-(3-hydroxypropyl)-5-oxo-1,2,4-triazol-1-yl]-2-[(1S)-2,2,2-trifluoro-1-methyl-ethoxy]pyridine-3-carboxamide;
- N-(5-Chloro-3-methyl-1H-pyrazol-4-yl)-6-[4-ethyl-3-(fluoromethyl)-5-oxo-1,2,4-triazol-1-yl]-5-fluoro-2-isopropoxy-pyridine-3-carboxamide;
- 6-[4-Ethyl-3-(hydroxymethyl)-5-oxo-1,2,4-triazol-1-yl]-5-fluoro-N-(3-methoxypyridazin-4-yl)-2-[(1S)-2,2,2-trifluoro-1-methyl-ethoxy]pyridine-3-carboxamide;
- N-(5-Chloro-2-methoxy-3-methyl-4-pyridyl)-6-[4-ethyl-3-(hydroxymethyl)-5-oxo-1,2,4-triazol-1-yl]-5-fluoro-2-[(1S)-2,2,2-trifluoro-1-methyl-ethoxy]pyridine-3-carboxamide;
- 6-[4-Ethyl-3-(hydroxymethyl)-5-oxo-1,2,4-triazol-1-yl]-5-fluoro-N-[3-methyl-5-(trifluoromethyl)-1H-pyrazol-4-yl]-2-[(1S)-2,2,2-trifluoro-1-methyl-ethoxy]pyridine-3-carboxamide;
- N-[3-Chloro-5-(trifluoromethyl)-1H-pyrazol-4-yl]-6-[4-ethyl-3-(hydroxymethyl)-5-oxo-1,2,4-triazol-1-yl]-5-fluoro-2-[(1S)-2,2,2-trifluoro-1-methyl-ethoxy]pyridine-3-carboxamide;
- N-(6-Chloro-2-methoxy-4-methyl-3-pyridyl)-6-[4-ethyl-3-(hydroxymethyl)-5-oxo-1,2,4-triazol-1-yl]-5-fluoro-2-[(1S)-2,2,2-trifluoro-1-methyl-ethoxy]pyridine-3-carboxamide;
- 6-[4-Ethyl-3-(hydroxymethyl)-5-oxo-1,2,4-triazol-1-yl]-5-fluoro-N-(2-methoxy-4,6-dimethyl-3-pyridyl)-2-[(1S)-2,2,2-trifluoro-1-methyl-ethoxy]pyridine-3-carboxamide;
- N-(5-Chloro-3-methyl-1H-pyrazol-4-yl)-5-fluoro-6-[3-(fluoromethyl)-4-(2-hydroxyethyl)-5-oxo-1,2,4-triazol-1-yl]-2-[(1S)-2,2,2-trifluoro-1-methyl-ethoxy]pyridine-3-carboxamide;
- N-(2-Chloro-4-methyl-3-pyridyl)-5-fluoro-6-[3-(fluoromethyl)-4-(2-hydroxyethyl)-5-oxo-1,2,4-triazol-1-yl]-2-[(1S)-2,2,2-trifluoro-1-methyl-ethoxy]pyridine-3-carboxamide;
- N-(3-Cyano-5-fluoro-2-methoxy-4-pyridyl)-6-[4-ethyl-3-(hydroxymethyl)-5-oxo-1,2,4-triazol-1-yl]-5-fluoro-2-[(1S)-2,2,2-trifluoro-1-methyl-ethoxy]pyridine-3-carboxamide;
- N-(3-Chloro-5-methoxy-2-pyridyl)-6-[4-ethyl-3-(hydroxymethyl)-5-oxo-1,2,4-triazol-1-yl]-5-fluoro-2-[(1S)-2,2,2-trifluoro-1-methyl-ethoxy]pyridine-3-carboxamide;
- N-(2,6-Dimethoxyphenyl)-6-[4-ethyl-3-(hydroxymethyl)-5-oxo-1,2,4-triazol-1-yl]-5-fluoro-2-[(1S)-2,2,2-trifluoro-1-methyl-ethoxy]pyridine-3-carboxamide;
- 6-[4-Ethyl-3-(hydroxymethyl)-5-oxo-1,2,4-triazol-1-yl]-5-fluoro-N-(o-tolyl)-2-[(1S)-2,2,2-trifluoro-1-methyl-ethoxy]pyridine-3-carboxamide;
- 6-[4-Ethyl-3-(hydroxymethyl)-5-oxo-1,2,4-triazol-1-yl]-5-fluoro-N-(3-methoxy-5-methyl-1H-pyrazol-4-yl)-2-[(1S)-2,2,2-trifluoro-1-methyl-ethoxy]pyridine-3-carboxamide;
- N-(3,5-Dimethoxy-4-pyridyl)-6-[4-ethyl-3-(hydroxymethyl)-5-oxo-1,2,4-triazol-1-yl]-5-fluoro-2-[(1S)-2,2,2-trifluoro-1-methyl-ethoxy]pyridine-3-carboxamide;
- N-(3,5-Dichloro-1H-pyrazol-4-yl)-6-[4-ethyl-3-(hydroxymethyl)-5-oxo-1,2,4-triazol-1-yl]-5-fluoro-2-[(1S)-2,2,2-trifluoro-1-methyl-ethoxy]pyridine-3-carboxamide;
- N-[3-(Difluoromethyl)-5-methyl-1H-pyrazol-4-yl]-6-[4-ethyl-3-(hydroxymethyl)-5-oxo-1,2,4-triazol-1-yl]-5-fluoro-2-[(1S)-2,2,2-trifluoro-1-methyl-ethoxy]pyridine-3-carboxamide;
- 6-[4-Ethyl-3-(hydroxymethyl)-5-oxo-1,2,4-triazol-1-yl]-5-fluoro-N-(4-fluoro-2-methoxy-3-pyridyl)-2-[(1S)-2,2,2-trifluoro-1-methyl-ethoxy]pyridine-3-carboxamide;
- N-(4-Chloro-2-methoxy-3-pyridyl)-6-[4-ethyl-3-(hydroxymethyl)-5-oxo-1,2,4-triazol-1-yl]-5-fluoro-2-[(1S)-2,2,2-trifluoro-1-methyl-ethoxy]pyridine-3-carboxamide;
- (Racemic)-6-[4-Ethyl-3-(1-hydroxyethyl)-5-oxo-1,2,4-triazol-1-yl]-5-fluoro-N-[3-methyl-5-(trifluoromethyl)-1H-pyrazol-4-yl]-2-(2,2,2-trifluoro-1-methyl-ethoxy)pyridine-3-carboxamide;
- and
- 6-[4-Ethyl-3-(1-hydroxy-1-methyl-ethyl)-5-oxo-1,2,4-triazol-1-yl]-5-fluoro-N-[3-methyl-5-(trifluoromethyl)-1H-pyrazol-4-yl]-2-[(1S)-2,2,2-trifluoro-1-methyl-ethoxy]pyridine-3-carboxamide;
- or a pharmaceutically acceptable salt, solvate, stereoisomer, tautomer, isotopic variant, or N-oxide thereof.
127 more elements
A compound selected from the group consisting of:
- (S)-N-(2-Chloro-4-methylpyridin-3-yl)-6-(4-ethyl-3-(hydroxymethyl)-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl)-5-fluoro-2-((1,1,1-trifluoropropan-2-yl)oxy)nicotinamide;
- (S)-N-(5-Chloro-3-methyl-1H-pyrazol-4-yl)-6-(4-ethyl-3-(hydroxymethyl)-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl)-5-fluoro-2-((1,1,1-trifluoropropan-2-yl)oxy)nicotinamide;
- (S)-N-(3-Chloro-2-methoxy-5-methylpyridin-4-yl)-6-(4-ethyl-3-(hydroxymethyl)-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl)-5-fluoro-2-((1,1,1-trifluoropropan-2-yl)oxy)nicotinamide;
- (S)-6-(4-Ethyl-3-(hydroxymethyl)-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl)-5-fluoro-N-(2-methoxy-4-methylpyridin-3-yl)-2-((1,1,1-trifluoropropan-2-yl)oxy)nicotinamide;
- 6-[4-Ethyl-3-(hydroxymethyl)-5-oxo-1,2,4-triazol-1-yl]-5-fluoro-N-[3-methyl-5-(trifluoromethyl)-1H-pyrazol-4-yl]-2-[(1S)-2,2,2-trifluoro-1-methyl-ethoxy]pyridine-3-carboxamide;
- and
- 6-[4-Ethyl-3-(hydroxymethyl)-5-oxo-1,2,4-triazol-1-yl]-5-fluoro-N-(2-methoxy-3,5-dimethyl-4-pyridyl)-2-[(1S)-2,2,2-trifluoro-1-methyl-ethoxy]pyridine-3-carboxamide;
- or a pharmaceutically acceptable salt, solvate, stereoisomer, tautomer, isotopic variant, or N-oxide thereof.
5 more elements
A compound selected from the group consisting of:
- or a pharmaceutically acceptable salt, solvate, stereoisomer, tautomer, isotopic variant, or N-oxide thereof.
Dependencies are inferred from the claim text.