KR20120047313A - 티로신 키나제 조절인자로서의 화합물 - Google Patents
티로신 키나제 조절인자로서의 화합물 Download PDFInfo
- Publication number
- KR20120047313A KR20120047313A KR1020127008527A KR20127008527A KR20120047313A KR 20120047313 A KR20120047313 A KR 20120047313A KR 1020127008527 A KR1020127008527 A KR 1020127008527A KR 20127008527 A KR20127008527 A KR 20127008527A KR 20120047313 A KR20120047313 A KR 20120047313A
- Authority
- KR
- South Korea
- Prior art keywords
- amino
- pyridin
- group
- pyrrole
- carbonyl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Withdrawn
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- 150000001875 compounds Chemical class 0.000 title claims abstract description 98
- 102000004022 Protein-Tyrosine Kinases Human genes 0.000 title abstract description 19
- 108090000412 Protein-Tyrosine Kinases Proteins 0.000 title abstract description 19
- 238000011282 treatment Methods 0.000 claims abstract description 14
- 125000000217 alkyl group Chemical group 0.000 claims description 137
- 239000000203 mixture Substances 0.000 claims description 127
- -1 C 1 -C 5 alkoxy Chemical group 0.000 claims description 124
- 238000000034 method Methods 0.000 claims description 112
- 239000001257 hydrogen Substances 0.000 claims description 92
- 229910052739 hydrogen Inorganic materials 0.000 claims description 92
- 150000002431 hydrogen Chemical class 0.000 claims description 86
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 69
- 125000004448 alkyl carbonyl group Chemical group 0.000 claims description 64
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 50
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 50
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 48
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 47
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 43
- 229910052757 nitrogen Inorganic materials 0.000 claims description 39
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 37
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 35
- 125000003118 aryl group Chemical group 0.000 claims description 35
- 125000004391 aryl sulfonyl group Chemical group 0.000 claims description 35
- 125000004441 haloalkylsulfonyl group Chemical group 0.000 claims description 35
- 229910052760 oxygen Inorganic materials 0.000 claims description 33
- 229910052717 sulfur Inorganic materials 0.000 claims description 30
- 125000003342 alkenyl group Chemical group 0.000 claims description 29
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 28
- 125000001072 heteroaryl group Chemical group 0.000 claims description 24
- 125000005842 heteroatom Chemical group 0.000 claims description 24
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 23
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 21
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- 125000003545 alkoxy group Chemical group 0.000 claims description 18
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- 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 claims description 15
- 150000003839 salts Chemical class 0.000 claims description 14
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- 125000002619 bicyclic group Chemical group 0.000 claims description 13
- 125000002950 monocyclic group Chemical group 0.000 claims description 13
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 12
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- 125000001624 naphthyl group Chemical group 0.000 claims description 12
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 12
- 125000000369 oxido group Chemical group [*]=O 0.000 claims description 12
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- 125000005078 alkoxycarbonylalkyl group Chemical group 0.000 claims description 11
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- 150000002367 halogens Chemical class 0.000 claims description 10
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- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 8
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- LOASYNCSCBFHTC-UHFFFAOYSA-N 5-[4-[3-[(3-methylfuran-2-carbonyl)amino]phenoxy]pyridin-2-yl]-1h-pyrrole-3-carboxylic acid Chemical compound C1=COC(C(=O)NC=2C=C(OC=3C=C(N=CC=3)C=3NC=C(C=3)C(O)=O)C=CC=2)=C1C LOASYNCSCBFHTC-UHFFFAOYSA-N 0.000 claims description 7
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 7
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 7
- ORTFAQDWJHRMNX-UHFFFAOYSA-N hydroxidooxidocarbon(.) Chemical group O[C]=O ORTFAQDWJHRMNX-UHFFFAOYSA-N 0.000 claims description 7
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 claims description 7
- 239000005483 tyrosine kinase inhibitor Substances 0.000 claims description 7
- IYDSQQHYVCHBKZ-UHFFFAOYSA-N 5-[4-[3-[(2-fluoro-5-methylphenyl)carbamoyl]phenoxy]pyridin-2-yl]-1h-pyrrole-3-carboxylic acid Chemical compound CC1=CC=C(F)C(NC(=O)C=2C=C(OC=3C=C(N=CC=3)C=3NC=C(C=3)C(O)=O)C=CC=2)=C1 IYDSQQHYVCHBKZ-UHFFFAOYSA-N 0.000 claims description 6
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 6
- 125000005083 alkoxyalkoxy group Chemical group 0.000 claims description 6
- 125000005160 aryl oxy alkyl group Chemical group 0.000 claims description 6
- 125000005243 carbonyl alkyl group Chemical group 0.000 claims description 6
- 125000004122 cyclic group Chemical group 0.000 claims description 6
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 6
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- NKTLRPAMUNWXJM-UHFFFAOYSA-N methyl 5-[4-[3-[(2-fluoro-5-methylphenyl)carbamoyl]phenoxy]pyridin-2-yl]-1h-pyrrole-3-carboxylate Chemical compound COC(=O)C1=CNC(C=2N=CC=C(OC=3C=C(C=CC=3)C(=O)NC=3C(=CC=C(C)C=3)F)C=2)=C1 NKTLRPAMUNWXJM-UHFFFAOYSA-N 0.000 claims description 6
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- PZDHDXJQAMOBKZ-UHFFFAOYSA-N 2-hydroxyethyl 5-[4-[3-[(3-methylfuran-2-carbonyl)amino]phenoxy]pyridin-2-yl]-1h-pyrrole-3-carboxylate Chemical compound C1=COC(C(=O)NC=2C=C(OC=3C=C(N=CC=3)C=3NC=C(C=3)C(=O)OCCO)C=CC=2)=C1C PZDHDXJQAMOBKZ-UHFFFAOYSA-N 0.000 claims description 5
- YVBJJWJXRFAJEF-UHFFFAOYSA-N 3-methyl-n-[3-[2-(1h-pyrrol-2-yl)pyridin-4-yl]oxyphenyl]furan-2-carboxamide Chemical compound C1=COC(C(=O)NC=2C=C(OC=3C=C(N=CC=3)C=3NC=CC=3)C=CC=2)=C1C YVBJJWJXRFAJEF-UHFFFAOYSA-N 0.000 claims description 5
- NMDGZSOTLLTSKB-UHFFFAOYSA-N 3-methyl-n-[4-[2-(1h-pyrrol-2-yl)pyridin-4-yl]oxyphenyl]furan-2-carboxamide Chemical compound C1=COC(C(=O)NC=2C=CC(OC=3C=C(N=CC=3)C=3NC=CC=3)=CC=2)=C1C NMDGZSOTLLTSKB-UHFFFAOYSA-N 0.000 claims description 5
- NXUSKSUIDVFHMV-UHFFFAOYSA-N 5-[4-[3-[(3-methylfuran-2-carbonyl)amino]anilino]pyridin-2-yl]-1h-pyrrole-3-carboxylic acid Chemical compound C1=COC(C(=O)NC=2C=C(NC=3C=C(N=CC=3)C=3NC=C(C=3)C(O)=O)C=CC=2)=C1C NXUSKSUIDVFHMV-UHFFFAOYSA-N 0.000 claims description 5
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- DYSHSHRKLARKDP-UHFFFAOYSA-N methyl 5-[4-[2-fluoro-5-[(2-fluoro-5-methylphenyl)carbamoyl]phenoxy]pyridin-2-yl]-1h-pyrrole-3-carboxylate Chemical class COC(=O)C1=CNC(C=2N=CC=C(OC=3C(=CC=C(C=3)C(=O)NC=3C(=CC=C(C)C=3)F)F)C=2)=C1 DYSHSHRKLARKDP-UHFFFAOYSA-N 0.000 claims description 5
- ZVSMCBXMMPTXPB-UHFFFAOYSA-N methyl 5-[4-[3-[(3-methylfuran-2-carbonyl)amino]anilino]pyridin-2-yl]-1h-pyrrole-3-carboxylate Chemical compound COC(=O)C1=CNC(C=2N=CC=C(NC=3C=C(NC(=O)C4=C(C=CO4)C)C=CC=3)C=2)=C1 ZVSMCBXMMPTXPB-UHFFFAOYSA-N 0.000 claims description 5
- UONKVPSAMIUNOO-UHFFFAOYSA-N methyl 5-[4-[3-[(3-methylfuran-2-carbonyl)amino]phenoxy]pyridin-2-yl]-1h-pyrrole-3-carboxylate Chemical compound COC(=O)C1=CNC(C=2N=CC=C(OC=3C=C(NC(=O)C4=C(C=CO4)C)C=CC=3)C=2)=C1 UONKVPSAMIUNOO-UHFFFAOYSA-N 0.000 claims description 5
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- QLKISZYEDUGZEX-UHFFFAOYSA-N 5-[4-[2-fluoro-5-[(2-fluoro-5-methylphenyl)carbamoyl]phenoxy]pyridin-2-yl]-n-hydroxy-1h-pyrrole-3-carboxamide Chemical compound CC1=CC=C(F)C(NC(=O)C=2C=C(OC=3C=C(N=CC=3)C=3NC=C(C=3)C(=O)NO)C(F)=CC=2)=C1 QLKISZYEDUGZEX-UHFFFAOYSA-N 0.000 claims description 4
- KUYVWUAGELSGSE-UHFFFAOYSA-N 5-[4-[3-[(2-fluoro-5-methylphenyl)carbamoyl]phenoxy]pyridin-2-yl]-n-hydroxy-1h-pyrrole-3-carboxamide Chemical compound CC1=CC=C(F)C(NC(=O)C=2C=C(OC=3C=C(N=CC=3)C=3NC=C(C=3)C(=O)NO)C=CC=2)=C1 KUYVWUAGELSGSE-UHFFFAOYSA-N 0.000 claims description 4
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| US9902709B2 (en) | 2014-04-08 | 2018-02-27 | Peking University Founder Group Co., Ltd. | Polysubstituted pyridine compound, preparation method, use and pharmaceutical composition |
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| US7431710B2 (en) | 2002-04-08 | 2008-10-07 | Glaukos Corporation | Ocular implants with anchors and methods thereof |
| CN102131801B (zh) | 2008-06-25 | 2015-04-08 | 福拉姆医药股份有限公司 | 1,2-二取代的杂环化合物 |
| WO2010045095A1 (en) | 2008-10-14 | 2010-04-22 | Ning Xi | Compounds and methods of use |
| CA2752421C (en) | 2009-03-21 | 2013-08-06 | Ning Xi | Amino ester derivatives, salts thereof and methods of use |
| PL2617420T3 (pl) | 2009-05-07 | 2016-04-29 | Forum Pharmaceuticals Inc | Heterocykliczne związki fenoksymetylu |
| US12478503B2 (en) | 2009-05-18 | 2025-11-25 | Glaukos Corporation | Implants with controlled drug delivery features and methods of using same |
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| EP4289416A3 (en) | 2009-05-18 | 2024-01-03 | Dose Medical Corporation | Drug eluting ocular implant |
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