ES2378670T3 - Aril ureas como inhibidores de cinasas - Google Patents
Aril ureas como inhibidores de cinasas Download PDFInfo
- Publication number
- ES2378670T3 ES2378670T3 ES05007027T ES05007027T ES2378670T3 ES 2378670 T3 ES2378670 T3 ES 2378670T3 ES 05007027 T ES05007027 T ES 05007027T ES 05007027 T ES05007027 T ES 05007027T ES 2378670 T3 ES2378670 T3 ES 2378670T3
- Authority
- ES
- Spain
- Prior art keywords
- amino
- phenyl
- trifluoromethyl
- phenoxy
- 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.)
- Expired - Lifetime
Links
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- 229940043355 kinase inhibitor Drugs 0.000 title description 7
- 239000003757 phosphotransferase inhibitor Substances 0.000 title description 7
- 150000003672 ureas Chemical class 0.000 title description 6
- 150000001875 compounds Chemical class 0.000 claims abstract description 169
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 61
- -1 aryl ureas Chemical class 0.000 claims abstract description 60
- 238000000034 method Methods 0.000 claims abstract description 41
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 40
- 201000011510 cancer Diseases 0.000 claims abstract description 31
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- 208000035475 disorder Diseases 0.000 claims abstract description 18
- 208000001132 Osteoporosis Diseases 0.000 claims abstract description 9
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- 239000002253 acid Substances 0.000 claims description 24
- 229910052739 hydrogen Inorganic materials 0.000 claims description 24
- 150000003839 salts Chemical class 0.000 claims description 24
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- 239000000824 cytostatic agent Substances 0.000 claims description 19
- 231100000433 cytotoxic Toxicity 0.000 claims description 19
- 230000001472 cytotoxic effect Effects 0.000 claims description 19
- 238000002360 preparation method Methods 0.000 claims description 19
- 239000008194 pharmaceutical composition Substances 0.000 claims description 18
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 18
- 239000003795 chemical substances by application Substances 0.000 claims description 17
- 239000002254 cytotoxic agent Substances 0.000 claims description 17
- 241000124008 Mammalia Species 0.000 claims description 15
- 229940127089 cytotoxic agent Drugs 0.000 claims description 14
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- 238000007254 oxidation reaction Methods 0.000 claims description 9
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 9
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 8
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- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 5
- XMYQHJDBLRZMLW-UHFFFAOYSA-N methanolamine Chemical compound NCO XMYQHJDBLRZMLW-UHFFFAOYSA-N 0.000 claims description 5
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 4
- FDKXTQMXEQVLRF-ZHACJKMWSA-N (E)-dacarbazine Chemical compound CN(C)\N=N\c1[nH]cnc1C(N)=O FDKXTQMXEQVLRF-ZHACJKMWSA-N 0.000 claims description 4
- KCATYYYVKFCWJQ-UHFFFAOYSA-N 4-[4-[[4-bromo-3-(trifluoromethyl)phenyl]carbamoylamino]phenoxy]pyridine-2-carboxamide Chemical compound C1=NC(C(=O)N)=CC(OC=2C=CC(NC(=O)NC=3C=C(C(Br)=CC=3)C(F)(F)F)=CC=2)=C1 KCATYYYVKFCWJQ-UHFFFAOYSA-N 0.000 claims description 4
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- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 4
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 4
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- ZDZOTLJHXYCWBA-VCVYQWHSSA-N N-debenzoyl-N-(tert-butoxycarbonyl)-10-deacetyltaxol Chemical compound O([C@H]1[C@H]2[C@@](C([C@H](O)C3=C(C)[C@@H](OC(=O)[C@H](O)[C@@H](NC(=O)OC(C)(C)C)C=4C=CC=CC=4)C[C@]1(O)C3(C)C)=O)(C)[C@@H](O)C[C@H]1OC[C@]12OC(=O)C)C(=O)C1=CC=CC=C1 ZDZOTLJHXYCWBA-VCVYQWHSSA-N 0.000 claims description 4
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- DRTQHJPVMGBUCF-XVFCMESISA-N Uridine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-XVFCMESISA-N 0.000 claims description 4
- RJURFGZVJUQBHK-IIXSONLDSA-N actinomycin D Chemical compound C[C@H]1OC(=O)[C@H](C(C)C)N(C)C(=O)CN(C)C(=O)[C@@H]2CCCN2C(=O)[C@@H](C(C)C)NC(=O)[C@H]1NC(=O)C1=C(N)C(=O)C(C)=C2OC(C(C)=CC=C3C(=O)N[C@@H]4C(=O)N[C@@H](C(N5CCC[C@H]5C(=O)N(C)CC(=O)N(C)[C@@H](C(C)C)C(=O)O[C@@H]4C)=O)C(C)C)=C3N=C21 RJURFGZVJUQBHK-IIXSONLDSA-N 0.000 claims description 4
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 4
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- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/79—Acids; Esters
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/81—Amides; Imides
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/89—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members with hetero atoms directly attached to the ring nitrogen atom
Landscapes
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- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Pyridine Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
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| EP1158985B1 (en) | 1999-01-13 | 2011-12-28 | Bayer HealthCare LLC | OMEGA-CARBOXY ARYL SUBSTITUTED DIPHENYL UREAS AS p38 KINASE INHIBITORS |
| US7351834B1 (en) | 1999-01-13 | 2008-04-01 | Bayer Pharmaceuticals Corporation | ω-Carboxyaryl substituted diphenyl ureas as raf kinase inhibitors |
| US8124630B2 (en) | 1999-01-13 | 2012-02-28 | Bayer Healthcare Llc | ω-carboxyaryl substituted diphenyl ureas as raf kinase inhibitors |
| AU2003209119A1 (en) | 2002-02-11 | 2003-09-04 | Bayer Pharmaceuticals Corporation | Pyridine, quinoline, and isoquinoline n-oxides as kinase inhibitors |
| ES2425739T3 (es) | 2002-02-11 | 2013-10-17 | Bayer Healthcare Llc | Sorafenib-tosilato para el tratamiento de enfermedades caracterizadas por angiogénesis anormal |
| US7557129B2 (en) | 2003-02-28 | 2009-07-07 | Bayer Healthcare Llc | Cyanopyridine derivatives useful in the treatment of cancer and other disorders |
| AU2004247626B8 (en) | 2003-05-15 | 2011-05-19 | Arqule, Inc. | Imidazothiazoles and imidazoxazole derivatives as inhibitors of p38 |
| DE602004011340T2 (de) | 2003-05-20 | 2008-11-06 | Bayer Healthcare Llc | Diaryl-harnstoffe mit kinasehemmender wirkung |
| NZ544920A (en) | 2003-07-23 | 2009-11-27 | Bayer Healthcare Llc | 4{4-[3-(4-chloro-3-trifluoromethylphenyl)-ureido]-3-fluorophenoxy}-pyridine-2-carboxylic acid methylamide and metabolites for the treatment and prevention of diseases and conditions |
| CN1972925A (zh) * | 2004-01-30 | 2007-05-30 | 默克专利有限公司 | 双芳基脲类衍生物 |
| TW200530236A (en) | 2004-02-23 | 2005-09-16 | Chugai Pharmaceutical Co Ltd | Heteroaryl phenylurea |
| JP2007535565A (ja) | 2004-04-30 | 2007-12-06 | バイエル ファーマシューティカルス コーポレーション | 癌の治療に有用な置換ピラゾリル尿素誘導体 |
| WO2006010082A1 (en) | 2004-07-08 | 2006-01-26 | Arqule, Inc. | 1,4-disubstituted naphtalenes as inhibitors of p38 map kinase |
| US8877933B2 (en) * | 2004-09-29 | 2014-11-04 | Bayer Intellectual Property Gmbh | Thermodynamically stable form of a tosylate salt |
| AU2005297531B2 (en) * | 2004-10-13 | 2011-06-23 | Merck Patent Gmbh | Phenylurea derivatives used as inhibitors of tyrosinkinase for treating tumors |
| US8178672B2 (en) | 2004-10-19 | 2012-05-15 | Arqule, Inc. | Synthesis of imidazooxazole and imidazothiazole inhibitors of p38 MAP kinase |
| WO2006062982A2 (en) | 2004-12-07 | 2006-06-15 | Locus Pharmaceuticals, Inc. | Urea inhibitors of map kinases |
| WO2006062984A2 (en) | 2004-12-07 | 2006-06-15 | Locus Pharmaceuticals, Inc. | Inhibitors of protein kinases |
| UA93673C2 (ru) | 2005-03-07 | 2011-03-10 | Баер Шеринг Фарма Акциенгезельшафт | Фармацевтическая композиция, которая содержит омега-карбоксиарилзамещенную дифенилмочевину, для лечения paka |
| EP1921078B1 (en) | 2005-08-05 | 2013-01-09 | Chugai Seiyaku Kabushiki Kaisha | Multikinase inhibitor |
| AR062927A1 (es) * | 2006-10-11 | 2008-12-17 | Bayer Healthcare Ag | 4- [4-( [ [ 4- cloro-3-( trifluorometil) fenil) carbamoil] amino] -3- fluorofenoxi) -n- metilpiridin-2- carboxamida monohidratada |
| ES2429107T3 (es) | 2007-01-19 | 2013-11-13 | Bayer Healthcare Llc | Tratamiento de cánceres con una resistencia adquirida a los agentes inhibidores de KIT |
| EP2136809A4 (en) * | 2007-03-20 | 2012-01-04 | Curis Inc | INHIBITORS OF RAF KINASE CONTAINING A ZINC BINDING FRAGMENT |
| WO2009132397A1 (en) * | 2008-05-01 | 2009-11-05 | University Of South Australia | Methods and agents for modulating the level and/or activity of hif-2 alpha protein |
| JP5439494B2 (ja) | 2008-10-21 | 2014-03-12 | バイエル ヘルスケア エルエルシー | 肝細胞癌と関連するシグネチャ遺伝子の同定 |
| WO2010065893A1 (en) * | 2008-12-05 | 2010-06-10 | Arqule, Inc. | Raf inhibitors and their uses |
| FR2945210B1 (fr) * | 2009-05-07 | 2011-07-01 | Sanofi Aventis | Combinaison antitumorale comprenant l'ave8062 et le sorafenib |
| CN101717373B (zh) * | 2009-11-09 | 2012-06-20 | 东南大学 | 二芳基脲类衍生物及其用途 |
| AR081060A1 (es) | 2010-04-15 | 2012-06-06 | Bayer Schering Pharma Ag | Procedimiento para preparar 4-{4-[({[4-cloro-3-(trifluorometil)fenil]amino}carbonil)amino]-3-fluorofenoxi}-n-metilpiridin-2-carboxamida |
| CN103508961B (zh) * | 2012-06-26 | 2015-07-22 | 中美冠科生物技术（太仓）有限公司 | 抗肿瘤药物 |
| CN105181844A (zh) * | 2015-09-11 | 2015-12-23 | 江苏嘉逸医药有限公司 | 一种高效液相色谱法测定甲苯磺酸索拉非尼含量和有关物质的方法 |
| EP3500257B1 (en) * | 2016-08-17 | 2025-07-02 | Icahn School of Medicine at Mount Sinai | Kinase inhibitor compounds, compositions, and methods of treating cancer |
| GB201713975D0 (en) | 2017-08-31 | 2017-10-18 | Macrophage Pharma Ltd | Medical use |
| CN115380026B (zh) * | 2020-03-17 | 2023-11-07 | 南京明德新药研发有限公司 | 蛋白降解调节剂与其使用方法 |
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| US502504A (en) | 1893-08-01 | Hermann thoms | ||
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| DE523437C (de) | 1928-12-25 | 1931-05-05 | I G Farbenindustrie Akt Ges | Verfahren zur Darstellung von 5-Chlor- und 5-Brom-2-amino-1-alkyloxy- und 1-aralkyloxybenzolen |
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| DE925476C (de) | 1950-04-29 | 1955-03-21 | Variapat Ag | Verfahren zur Herstellung von farblosen, wasserloeslichen, trifluormethyl- und sulfonsaeuregruppenhaltigen, aliphatischen oder aromatischen Carbonsaeure- bzw. Sulfonsaeurearyliden |
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-
2003
- 2003-02-11 CA CA2475818A patent/CA2475818C/en not_active Expired - Fee Related
- 2003-02-11 AU AU2003209118A patent/AU2003209118A1/en not_active Abandoned
- 2003-02-11 CN CNB03803705XA patent/CN1318404C/zh not_active Expired - Lifetime
- 2003-02-11 ES ES05007027T patent/ES2378670T3/es not_active Expired - Lifetime
- 2003-02-11 US US10/361,859 patent/US8110587B2/en not_active Expired - Fee Related
- 2003-02-11 WO PCT/US2003/004109 patent/WO2003068746A1/en not_active Ceased
- 2003-02-11 JP JP2003567877A patent/JP4527401B2/ja not_active Expired - Fee Related
- 2003-02-11 SI SI200332098T patent/SI1580188T1/sl unknown
- 2003-02-11 AT AT05007027T patent/ATE529406T1/de active
- 2003-02-11 MX MXPA04007830A patent/MXPA04007830A/es active IP Right Grant
- 2003-02-11 DK DK05007027.5T patent/DK1580188T3/da active
- 2003-02-11 PT PT05007027T patent/PT1580188E/pt unknown
- 2003-02-11 EP EP03707848A patent/EP1474393A1/en not_active Withdrawn
- 2003-02-11 EP EP05007027A patent/EP1580188B9/en not_active Expired - Lifetime
-
2010
- 2010-04-08 JP JP2010089118A patent/JP5692696B2/ja not_active Expired - Fee Related
-
2012
- 2012-01-03 CY CY20121100002T patent/CY1113654T1/el unknown
- 2012-02-03 US US13/365,687 patent/US9181188B2/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| WO2003068746A8 (en) | 2005-05-06 |
| US20030216446A1 (en) | 2003-11-20 |
| US9181188B2 (en) | 2015-11-10 |
| DK1580188T3 (da) | 2012-02-06 |
| HK10797774A1 (en) | 2007-12-21 |
| EP1580188B9 (en) | 2012-05-23 |
| EP1580188A1 (en) | 2005-09-28 |
| SI1580188T1 (sl) | 2012-02-29 |
| MXPA04007830A (es) | 2005-07-01 |
| EP1580188B1 (en) | 2011-10-19 |
| JP4527401B2 (ja) | 2010-08-18 |
| AU2003209118A1 (en) | 2003-09-04 |
| US20120136157A1 (en) | 2012-05-31 |
| JP2005523278A (ja) | 2005-08-04 |
| CA2475818A1 (en) | 2003-08-21 |
| JP5692696B2 (ja) | 2015-04-01 |
| US8110587B2 (en) | 2012-02-07 |
| ATE529406T1 (de) | 2011-11-15 |
| PT1580188E (pt) | 2012-01-25 |
| JP2010195806A (ja) | 2010-09-09 |
| CN1318404C (zh) | 2007-05-30 |
| CY1113654T1 (el) | 2016-06-22 |
| CN1630638A (zh) | 2005-06-22 |
| CA2475818C (en) | 2011-07-19 |
| EP1474393A1 (en) | 2004-11-10 |
| WO2003068746A1 (en) | 2003-08-21 |
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