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US 11,952,363 B2Granted
Piperazine compounds for the treatment of autoimmune disease
AssigneeHoffmann-La Roche Inc.
InventorsFabian Dey, Zongxing Qiu, Wei Zhu, Ge Zou
Life of this patent
Estimating the term…
Abstract
The present invention relates to compounds of formula (I), wherein R1 to R4 are as described herein, and their pharmaceutically acceptable salt, enantiomer or diastereomer thereof, and compositions including the compounds and methods of using the compounds.
Claims14
A compound of formula (I),
- wherein:
- R1 is
- wherein R5 is cyano, C1-6alkoxy, C1-6alkyl or halogen;
- R2 is C1-6alkyl;
- R3 is R3a or —COR3b;
- wherein:
- R3a is phenyl substituted by piperazinyl and (hydroxyC1-6 alkyl)piperazinyl, pyridinyl substituted by piperazinyl, C1-6alkylpiperazinyl, 9-oxa-3,7-diaza-bicyclo[3.3.1]nonanyl, (halopyrrolidinyl)amino, (pyrrolidinylcarbonyl)piperazinyl or (((C1-6alkyl)2amino)C1-6alkylcarbonyl)piperazinyl, or pyrimidinyl substituted by piperazinyl or (((C1-6alkyl)2amino)C1-6alkylcarbonyl)piperazinyl;
- R3b is 7,8-dihydro-5H-1,6-naphthyridinyl substituted by piperazinyl, 3,4-dihydro-1H-isoquinolinyl substituted by piperazinyl, isoindolinyl substituted by piperazinyl, phenylamino substituted by piperazinyl, 1,2,3,4-tetrahydroisoquinolinyl, or C1-6 alkylpiperidinylpiperidinyl;
- R4 is C1-6alkyl or H;
- or a pharmaceutically acceptable salt, enantiomer or diastereomer thereof.
7 more elements
A compound selected from:
- 5-[(3R,5S)-3,5-Dimethyl-4-[(4-piperazin-1-ylphenyl)methyl]piperazin-1-yl]quinoline-8-carbonitrile;
- 4-[(3R,5R)-3,5-Dimethyl-4-[(4-piperazin-1-ylphenyl)methyl]piperazin-1-yl]quinoline-8-carbonitrile;
- 5-[(3R,5S)-3,5-Dimethyl-4-[(6-piperazin-1-yl-3-pyridyl)methyl]piperazin-1-yl]quinoline-8-carbonitrile;
- 5-[(3S,5R)-3,5-Dimethyl-4-[(5-piperazin-1-ylpyrimidin-2-yl)methyl]piperazin-1-yl]quinoline-8-carbonitrile;
- 5-[(3S,5R)-3,5-Dimethyl-4-[(5-piperazin-1-yl-2-pyridyl)methyl]piperazin-1-yl]quinoline-8-carbonitrile;
- 5-[(3S,5R)-4-[[5-[4-[2-(Dimethylamino)acetyl]piperazin-1-yl]pyrimidin-2-yl]methyl]-3,5-dimethyl-piperazin-1-yl]quinoline-8-carbonitrile;
- 5-[(3S,5R)-3,5-dimethyl-4-[[5-(4-methylpiperazin-1-yl)-2-pyridyl]methyl]piperazin-1-yl]quinoline-8-carbonitrile;
- 5-[(3S,5R)-3,5 -Dimethyl-4-[[5-(9-oxa-3,7-diazabicyclo[3.3.1]nonan-3-yl)-2-pyridyl]methyl]piperazin-1-yl]quinoline-8-carbonitrile;
- 5-[(3R,5S)-3,5 -Dimethyl-4-[[5-[[(3R,4S)-4-fluoropyrrolidin-3-yl]amino]-2-pyridyl]methyl]piperazin-1-yl]quinoline-8-carbonitrile;
- 5-[(3R,5S)-3,5 -Dimethyl-4-[[5-[4-(pyrrolidine-2-carbonyl)piperazin-1-yl]-2-pyridyl]methyl]piperazin-1-yl]quinoline-8-carbonitrile;
- 5-[(3S, 5R)-4-[[5-[4-[2-(Dimethylamino)acetyl]piperazin-1-yl]-2-pyridyl]methyl]-3,5-dimethyl-piperazin-1 -yl]quinoline-8-carbonitrile;
- 5-[(3R, 5S)-4-[[4-[2-(Hydroxymethyl)piperazin-1-yl]phenyl]methyl]-3,5-dimethyl-piperazin-1-yl]quinoline-8-carbonitrile;
- 5-[(3R,5S)-3,5-Dimethyl-4-[2-oxo-2-(2-piperazin-1-yl-7,8-dihydro-5H-1,6-naphthyridin-6-yl) ethyl]piperazin-1-yl]quinoline-8-carbonitrile;
- 5-[(3R,5S)-3,5-Dimethyl-4-[2-oxo-2-(6-piperazin-1-yl-3,4-dihydro-1H-isoquinolin-2-yl) ethyl]piperazin-1-yl]quinoline-8-carbonitrile;
- 5-[(3R,5S)-3,5-dimethyl-4-[2-oxo-2-(7-piperazin-1-yl-3,4-dihydro-1H-isoquinolin-2-yl) ethyl]piperazin-1-yl]quinoline-8-carbonitrile;
- 5-[(3R,5S)-3,5-Dimethyl-4-[2-oxo-2-(5-piperazin-1-ylisoindolin-2-yl)ethyl]piperazin-1-yl]quinoline-8-carbonitrile;
- 2-[4-(8-Cyano-5-quinolyl)-2-methyl-piperazin-1-yl]-N-(4-piperazin-1-ylphenyl)acetamide;
- 2-[4-(8-Cyano-5-quinolyl)-2-methyl-piperazin-1-yl]-N-(1,2,3,4-tetrahydroisoquinolin-6-yl) acetamide;
- and
- 5-[3-methyl-4-[2-[4-(1-methyl-4-piperidyl)-1-piperidyl]-2-oxo-ethyl]piperazin-1-yl]quinoline-8-carbonitrile;
- or a pharmaceutically acceptable salt, enantiomer or diastereomer thereof.
18 more elements
Dependencies are inferred from the claim text.