HUE032847T2 - Vegyületek és készítmények mint protein kináz inhibitorok - Google Patents

Info

Publication number

HUE032847T2

HUE032847T2 HUE14152945A HUE14152945A HUE032847T2 HU E032847 T2 HUE032847 T2 HU E032847T2 HU E14152945 A HUE14152945 A HU E14152945A HU E14152945 A HUE14152945 A HU E14152945A HU E032847 T2 HUE032847 T2 HU E032847T2

Authority

HU

Hungary

Prior art keywords

compound

mixture

alkyl

pyrazol

methyl

Prior art date

2009-08-28

Links

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• 150000001875 compounds Chemical class 0.000 title claims abstract description 236
• 238000002360 preparation method Methods 0.000 title claims description 7
• 239000003909 protein kinase inhibitor Substances 0.000 title description 3
• 229940045988 antineoplastic drug protein kinase inhibitors Drugs 0.000 title 1
• 238000000034 method Methods 0.000 claims abstract description 28
• 108091000080 Phosphotransferase Proteins 0.000 claims abstract description 17
• 102000020233 phosphotransferase Human genes 0.000 claims abstract description 17
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 15
• 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 12
• 208000035475 disorder Diseases 0.000 claims abstract description 8
• 239000000203 mixture Substances 0.000 claims description 165
• -1 C 1 -C 4 alkyl) Chemical group 0.000 claims description 76
• 125000000217 alkyl group Chemical group 0.000 claims description 59
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 35
• 206010028980 Neoplasm Diseases 0.000 claims description 33
• CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 28
• 229910052739 hydrogen Inorganic materials 0.000 claims description 25
• 239000001257 hydrogen Substances 0.000 claims description 25
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 24
• 239000003814 drug Substances 0.000 claims description 23
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 22
• 239000003112 inhibitor Substances 0.000 claims description 22
• 201000011510 cancer Diseases 0.000 claims description 21
• 238000011282 treatment Methods 0.000 claims description 21
• PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 20
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 20
• KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 claims description 18
• 125000003545 alkoxy group Chemical group 0.000 claims description 18
• 239000003795 chemical substances by application Substances 0.000 claims description 17
• 229910052736 halogen Inorganic materials 0.000 claims description 16
• 150000002367 halogens Chemical class 0.000 claims description 16
• 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 16
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• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 13
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 13
• 125000005843 halogen group Chemical group 0.000 claims description 13
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• FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 claims description 11
• 229930195725 Mannitol Natural products 0.000 claims description 11
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• 239000000594 mannitol Substances 0.000 claims description 11
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• 125000001072 heteroaryl group Chemical group 0.000 claims description 10
• 150000002431 hydrogen Chemical class 0.000 claims description 10
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• FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 claims description 9
• DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims description 9
• VIUAUNHCRHHYNE-JTQLQIEISA-N N-[(2S)-2,3-dihydroxypropyl]-3-(2-fluoro-4-iodoanilino)-4-pyridinecarboxamide Chemical compound OC[C@@H](O)CNC(=O)C1=CC=NC=C1NC1=CC=C(I)C=C1F VIUAUNHCRHHYNE-JTQLQIEISA-N 0.000 claims description 9
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• FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 claims description 7
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• 239000011734 sodium Substances 0.000 claims description 7
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• 150000004677 hydrates Chemical class 0.000 claims description 6
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• NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 claims description 5
• 229920001223 polyethylene glycol Polymers 0.000 claims description 5
• LIRYPHYGHXZJBZ-UHFFFAOYSA-N trametinib Chemical compound CC(=O)NC1=CC=CC(N2C(N(C3CC3)C(=O)C3=C(NC=4C(=CC(I)=CC=4)F)N(C)C(=O)C(C)=C32)=O)=C1 LIRYPHYGHXZJBZ-UHFFFAOYSA-N 0.000 claims description 5
• 229960004066 trametinib Drugs 0.000 claims description 5
• RCLQNICOARASSR-SECBINFHSA-N 3-[(2r)-2,3-dihydroxypropyl]-6-fluoro-5-(2-fluoro-4-iodoanilino)-8-methylpyrido[2,3-d]pyrimidine-4,7-dione Chemical compound FC=1C(=O)N(C)C=2N=CN(C[C@@H](O)CO)C(=O)C=2C=1NC1=CC=C(I)C=C1F RCLQNICOARASSR-SECBINFHSA-N 0.000 claims description 4
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 4
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• 102000001253 Protein Kinase Human genes 0.000 claims description 4
• CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims description 4
• 235000021355 Stearic acid Nutrition 0.000 claims description 4
• DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 claims description 4
• 235000010443 alginic acid Nutrition 0.000 claims description 4
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• OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 claims description 4
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