Piperidylpyrimidine derivatives as modulators of protein kinase inhibitors and of vascular endothelial growth factor receptor 2
AssigneeAllergan, Inc.
InventorsJulie A. Wurster, Thomas C. Malone, Clarence Eugene Hull, III, Sandhya Rao, Rong Yang, Richard Yee
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Abstract
This invention is directed to a compound of Formula I or a pharmaceutically acceptable salt thereof, wherein X, R1, R2, R3, R4, R5, R6 and R7 are as defined herein. The compounds of Formula I are useful as protein kinase (PK) inhibitors and can be used to treat such diseases as cancer, blood vessel proliferative disorders, fibrotic disorders, mesangial cell proliferative disorders, metabolic diseases inflammatory disorders and neurodegenerative disorders.
Claims12
A compound represented by Formula I, its enantiomers, diastereoisomers, or a pharmaceutically acceptable salt thereof:
- wherein:
- X is N;
- R1 is substituted or unsubstituted aromatic heterocycle;
- R2 is hydrogen;
- R3 is hydrogen;
- R4 is hydrogen or OR9;
- R5 is OR9 or hydrogen;
- R6 is F, OR9, or hydrogen;
- R7 is hydrogen;
- R9 is hydrogen or substituted or unsubstituted alkyl;
- and
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A compound represented by Formula I, its enantiomers, diastereoisomers, or a pharmaceutically acceptable salt thereof:
- X is N;
- R1 is substituted or unsubstituted aryl;
- R2 is hydrogen;
- R3 is hydrogen;
- R4 is hydrogen or OR9;
- R5 is OR9 or hydrogen;
- R6 is F, OR9 or hydrogen;
- R7 is hydrogen;
- and
- R9 is substituted or unsubstituted alkyl.
A compound selected from the group consisting of:
- 6-(pyridin-3-ylcarbonyl)-N-(3,4,5-trimethoxyphenyl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-amine;
- N-phenyl-6-(pyridin-3-ylcarbonyl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-amine;
- 2-anilino-N-pyridin-3-yl-7,8-dihydropyrido[4,3-d]pyrimidine-6(5H)-carboxamide;
- 6-benzoyl-N-[5-(ethylsulfonyl)-2-methoxyphenyl]-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-amine;
- N-(4-methoxyphenyl)-6-(pyridin-3-ylcarbonyl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-amine;
- N-(3-methoxyphenyl)-6-(pyridin-3-ylcarbonyl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-amine;
- N-(2-methoxyphenyl)-6-(pyridin-3-ylcarbonyl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-amine;
- N-(3-fluorophenyl)-2-(pyridin-3-ylcarbonyl)-1,2,3,4-tetrahydroisoquinolin-6-amine;
- 6-(3-methyl-2-furoyl)-N-(3,4,5-trimethoxyphenyl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-amine;
- 6-[(1,3-dimethyl-1H-pyrazol-5-yl)carbonyl]-N-(3,4,5-trimethoxyphenyl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-amine;
- 6-(2-thienylcarbonyl)-N-(3,4,5-trimethoxyphenyl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-amine;
- 6-isonicotinoyl-N-(3,4,5-trimethoxyphenyl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-amine;
- 6-(pyridin-2-ylcarbonyl)-N-(3,4,5-trimethoxyphenyl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-amine;
- N-(3,4-dimethoxyphenyl)-6-(pyridin-3-ylcarbonyl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-amine;
- N-(3,5-dimethoxyphenyl)-6-(pyridin-3-ylcarbonyl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-amine;
- methyl 2-[(3,4,5-trimethoxyphenyl)amino]-5,7-dihydro-6H-pyrrolo[3,4-d]pyrimidine-6-carboxylate;
- 2-[(3,4,5-trimethoxyphenyl)amino]-5,7-dihydro-6H-pyrrolo[3,4-d]pyrimidine-6-carboxamide;
- and
- 7-(pyridin-3-ylcarbonyl)-N-(3,4,5-trimethoxyphenyl)-5,6,7,8-tetrahydro-2,7-naphthyridin-3-amine,
- or a pharmaceutically acceptable salt thereof.
A compound, selected from:
- N-(1-methyl-1H-pyrazol-5-yl)-6-(pyridin-3-ylcarbonyl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-amine;
- and
- 2-(pyridin-3-ylcarbonyl)-N-3-thienyl-1,2,3,4-tetrahydroisoquinolin-6-amine,
- or a pharmaceutically acceptable salt thereof.
Dependencies are inferred from the claim text.