ZA200607220B - Bisarylurea derivatives - Google Patents
Bisarylurea derivatives Download PDFInfo
- Publication number
- ZA200607220B ZA200607220B ZA200607220A ZA200607220A ZA200607220B ZA 200607220 B ZA200607220 B ZA 200607220B ZA 200607220 A ZA200607220 A ZA 200607220A ZA 200607220 A ZA200607220 A ZA 200607220A ZA 200607220 B ZA200607220 B ZA 200607220B
- Authority
- ZA
- South Africa
- Prior art keywords
- phenyl
- phenoxy
- ureido
- pyridine
- carboxylic acid
- Prior art date
Links
- -1 alkylenecycloaikyl Chemical group 0.000 claims description 204
- 150000001875 compounds Chemical class 0.000 claims description 129
- 125000004432 carbon atom Chemical group C* 0.000 claims description 117
- 125000000217 alkyl group Chemical group 0.000 claims description 114
- 125000001424 substituent group Chemical group 0.000 claims description 67
- 229910052739 hydrogen Inorganic materials 0.000 claims description 43
- 125000003545 alkoxy group Chemical group 0.000 claims description 40
- 229910052760 oxygen Inorganic materials 0.000 claims description 36
- 229910052717 sulfur Inorganic materials 0.000 claims description 36
- 206010028980 Neoplasm Diseases 0.000 claims description 30
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 25
- 125000000623 heterocyclic group Chemical group 0.000 claims description 24
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 22
- 229910052799 carbon Inorganic materials 0.000 claims description 21
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 20
- 150000003839 salts Chemical class 0.000 claims description 19
- 239000012453 solvate Substances 0.000 claims description 17
- 208000035475 disorder Diseases 0.000 claims description 16
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 16
- 125000005842 heteroatom Chemical group 0.000 claims description 16
- 125000004043 oxo group Chemical group O=* 0.000 claims description 16
- 239000000203 mixture Substances 0.000 claims description 15
- 108010077182 raf Kinases Proteins 0.000 claims description 15
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- 238000000034 method Methods 0.000 claims description 11
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- 229910052757 nitrogen Inorganic materials 0.000 claims description 10
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 claims description 9
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 9
- 239000008194 pharmaceutical composition Substances 0.000 claims description 9
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- 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 8
- 230000033115 angiogenesis Effects 0.000 claims description 8
- 125000006615 aromatic heterocyclic group Chemical group 0.000 claims description 8
- 150000004945 aromatic hydrocarbons Chemical class 0.000 claims description 7
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 7
- GVNVAWHJIKLAGL-UHFFFAOYSA-N 2-(cyclohexen-1-yl)cyclohexan-1-one Chemical compound O=C1CCCCC1C1=CCCCC1 GVNVAWHJIKLAGL-UHFFFAOYSA-N 0.000 claims description 6
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- 229910052801 chlorine Inorganic materials 0.000 claims description 4
- 229910052731 fluorine Inorganic materials 0.000 claims description 4
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- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 4
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- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 4
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- 229910052740 iodine Inorganic materials 0.000 claims description 3
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- PRRGGFAJKGXIFY-UHFFFAOYSA-N 4-[4-[[4-chloro-2-[2-(diethylamino)ethoxy]-5-methylphenyl]carbamoylamino]phenoxy]-n-methylpyridine-2-carboxamide Chemical compound CCN(CC)CCOC1=CC(Cl)=C(C)C=C1NC(=O)NC(C=C1)=CC=C1OC1=CC=NC(C(=O)NC)=C1 PRRGGFAJKGXIFY-UHFFFAOYSA-N 0.000 claims description 2
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- 125000003635 2-dimethylaminoethoxy group Chemical group [H]C([H])([H])N(C([H])([H])[H])C([H])([H])C([H])([H])O* 0.000 claims 2
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- QZEBRYLREGQEDK-UHFFFAOYSA-N 1-(4-piperidin-4-yloxyphenyl)-3-(4-pyridin-4-yloxyphenyl)urea Chemical compound C=1C=C(OC=2C=CN=CC=2)C=CC=1NC(=O)NC(C=C1)=CC=C1OC1CCNCC1 QZEBRYLREGQEDK-UHFFFAOYSA-N 0.000 claims 1
- HGCDJDCNKPDWSW-UHFFFAOYSA-N 1-[4-[2-(dimethylamino)ethoxy]phenyl]-3-(4-pyridin-4-yloxyphenyl)urea Chemical compound C1=CC(OCCN(C)C)=CC=C1NC(=O)NC(C=C1)=CC=C1OC1=CC=NC=C1 HGCDJDCNKPDWSW-UHFFFAOYSA-N 0.000 claims 1
- KWYWZVCWJGKHAZ-UHFFFAOYSA-N 1-[4-hydroxy-3-(trifluoromethyl)phenyl]-3-(4-pyridin-4-yloxyphenyl)urea Chemical compound C1=C(C(F)(F)F)C(O)=CC=C1NC(=O)NC(C=C1)=CC=C1OC1=CC=NC=C1 KWYWZVCWJGKHAZ-UHFFFAOYSA-N 0.000 claims 1
- OCPOGRCXGWHWBW-UHFFFAOYSA-N 1-[4-phenylmethoxy-3-(trifluoromethyl)phenyl]-3-(4-pyridin-4-yloxyphenyl)urea Chemical compound C=1C=C(OCC=2C=CC=CC=2)C(C(F)(F)F)=CC=1NC(=O)NC(C=C1)=CC=C1OC1=CC=NC=C1 OCPOGRCXGWHWBW-UHFFFAOYSA-N 0.000 claims 1
- 125000000872 2-diethylaminoethoxy group Chemical group [H]C([H])([H])C([H])([H])N(C([H])([H])C([H])([H])[H])C([H])([H])C([H])([H])O* 0.000 claims 1
- LYWKNMHMMMCXDR-UHFFFAOYSA-N 4-[3-[[2-(2-aminoethoxy)-4-chloro-5-methylphenyl]carbamoylamino]phenoxy]-n-methylpyridine-2-carboxamide Chemical compound C1=NC(C(=O)NC)=CC(OC=2C=C(NC(=O)NC=3C(=CC(Cl)=C(C)C=3)OCCN)C=CC=2)=C1 LYWKNMHMMMCXDR-UHFFFAOYSA-N 0.000 claims 1
- HJTOJIUFULTJFI-UHFFFAOYSA-N 4-[3-[[3-[2-(methylamino)ethoxy]-2-(trifluoromethyl)phenyl]carbamoylamino]phenoxy]pyridine-2-carboxylic acid Chemical compound CNCCOC1=CC=CC(NC(=O)NC=2C=C(OC=3C=C(N=CC=3)C(O)=O)C=CC=2)=C1C(F)(F)F HJTOJIUFULTJFI-UHFFFAOYSA-N 0.000 claims 1
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- SLPTWVLHHVRCDF-UHFFFAOYSA-N 4-[3-[[4-chloro-3-(2-pyrrolidin-1-ylethoxy)-2-(trifluoromethyl)phenyl]carbamoylamino]phenoxy]-n-methylpyridine-2-carboxamide Chemical compound C1=NC(C(=O)NC)=CC(OC=2C=C(NC(=O)NC=3C(=C(OCCN4CCCC4)C(Cl)=CC=3)C(F)(F)F)C=CC=2)=C1 SLPTWVLHHVRCDF-UHFFFAOYSA-N 0.000 claims 1
- JVMIMUUDXVQTES-UHFFFAOYSA-N 4-[4-[(2-methoxy-5-methylsulfonylphenyl)carbamoylamino]phenoxy]-n-methylpyridine-2-carboxamide Chemical compound C1=NC(C(=O)NC)=CC(OC=2C=CC(NC(=O)NC=3C(=CC=C(C=3)S(C)(=O)=O)OC)=CC=2)=C1 JVMIMUUDXVQTES-UHFFFAOYSA-N 0.000 claims 1
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- LJBFBLTWDNDNOQ-UHFFFAOYSA-N 4-[4-[[2-methoxy-5-(2-phenylpropan-2-yl)phenyl]carbamoylamino]phenoxy]-n-methylpyridine-2-carboxamide Chemical compound C1=NC(C(=O)NC)=CC(OC=2C=CC(NC(=O)NC=3C(=CC=C(C=3)C(C)(C)C=3C=CC=CC=3)OC)=CC=2)=C1 LJBFBLTWDNDNOQ-UHFFFAOYSA-N 0.000 claims 1
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- HXXAUIXTYRHFNO-UHFFFAOYSA-N n-methylpyridine-2-carboxamide Chemical compound CNC(=O)C1=CC=CC=N1 HXXAUIXTYRHFNO-UHFFFAOYSA-N 0.000 claims 1
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- POHGCTFPPUJFEA-UHFFFAOYSA-N tert-butyl 4-[2-[[4-[2-(methylcarbamoyl)pyridin-4-yl]oxyphenyl]carbamoylamino]phenyl]piperazine-1-carboxylate Chemical compound C1=NC(C(=O)NC)=CC(OC=2C=CC(NC(=O)NC=3C(=CC=CC=3)N3CCN(CC3)C(=O)OC(C)(C)C)=CC=2)=C1 POHGCTFPPUJFEA-UHFFFAOYSA-N 0.000 claims 1
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- 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
- C07D213/82—Amides; Imides in position 3
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
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- C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
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EP (1) | EP1730111A2 (ko) |
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US8124630B2 (en) | 1999-01-13 | 2012-02-28 | Bayer Healthcare Llc | ω-carboxyaryl substituted diphenyl ureas as raf kinase inhibitors |
ATE556713T1 (de) | 1999-01-13 | 2012-05-15 | Bayer Healthcare Llc | Omega-carboxyarylsubstituierte-diphenyl- harnstoffe als p38-kinasehemmer |
AU2003209116A1 (en) | 2002-02-11 | 2003-09-04 | Bayer Pharmaceuticals Corporation | Aryl ureas with angiogenesis inhibiting activity |
JP4860474B2 (ja) | 2003-05-20 | 2012-01-25 | バイエル、ファーマシューテイカルズ、コーポレイション | Pdgfrによって仲介される病気のためのジアリール尿素 |
DK1663978T3 (da) | 2003-07-23 | 2008-04-07 | Bayer Pharmaceuticals Corp | Fluorsubstitueret omega-carboxyaryl-diphenylurinstof til behandling og forebyggelse af sygdomme og lidelser |
WO2005110994A2 (en) | 2004-04-30 | 2005-11-24 | Bayer Pharmaceuticals Corporation | Substituted pyrazolyl urea derivatives useful in the treatment of cancer |
GB0512324D0 (en) | 2005-06-16 | 2005-07-27 | Novartis Ag | Organic compounds |
WO2006040056A1 (en) * | 2004-10-13 | 2006-04-20 | Merck Patent Gmbh | Heterocyclic substituted bisarylurea derivatives as kinase inhibitors |
WO2007064872A2 (en) * | 2005-12-01 | 2007-06-07 | Bayer Healthcare Llc | Urea compounds useful in the treatment of cancer |
US8580798B2 (en) | 2005-12-21 | 2013-11-12 | Bayer Intellectual Property Gmbh | Substituted pyrimidine derivatives useful in the treatment of cancer and other disorders |
TW200804349A (en) * | 2005-12-23 | 2008-01-16 | Kalypsys Inc | Novel substituted pyrimidinyloxy ureas as inhibitors of protein kinases |
AU2007346735A1 (en) * | 2006-03-21 | 2007-09-27 | The European Molecular Biology Laboratory | Agents that disrupt cellular replication and their use in inhibiting pathological conditions |
AU2007236321A1 (en) * | 2006-04-12 | 2007-10-18 | Merck Patent Gmbh | N-oxides of heterocyclic substituted bisarylureas for treating kinase-mediated diseases |
EP1992344A1 (en) | 2007-05-18 | 2008-11-19 | Institut Curie | P38 alpha as a therapeutic target in pathologies linked to FGFR3 mutation |
RU2012114902A (ru) | 2009-09-16 | 2013-10-27 | Авила Терапьютикс, Инк. | Конъюгаты и ингибиторы протеинкиназы |
CN101717373B (zh) * | 2009-11-09 | 2012-06-20 | 东南大学 | 二芳基脲类衍生物及其用途 |
TW201124398A (en) * | 2009-12-04 | 2011-07-16 | Daiichi Sankyo Co Ltd | Quinazoline derivatives |
BR112012015721A2 (pt) | 2009-12-30 | 2017-09-26 | Avila Therapeutics Inc | modificação covalente de proteínas dirigida por ligante |
EP2542086A4 (en) * | 2010-03-01 | 2013-09-04 | Myrexis Inc | COMPOUNDS AND ITS THERAPEUTIC USE |
US8912184B1 (en) | 2010-03-01 | 2014-12-16 | Alzheimer's Institute Of America, Inc. | Therapeutic and diagnostic methods |
CN101830847B (zh) * | 2010-05-18 | 2012-10-10 | 张南 | 抗癌用化合物及制备方法 |
CN102617458A (zh) * | 2010-05-18 | 2012-08-01 | 张南 | 抗癌用化合物的制备方法 |
CN102408426B (zh) * | 2011-09-14 | 2013-07-10 | 湖南有色凯铂生物药业有限公司 | 取代的芳香脲类化合物及其作为抗癌药物的应用 |
US9408885B2 (en) | 2011-12-01 | 2016-08-09 | Vib Vzw | Combinations of therapeutic agents for treating melanoma |
CN103319402B (zh) * | 2012-03-22 | 2015-01-14 | 齐鲁制药有限公司 | 二苯基硫脲类衍生物及其制备方法和应用 |
CN103788065A (zh) * | 2012-10-31 | 2014-05-14 | 韩冰 | 一类保护移植器官的化合物及其用途 |
WO2018039467A1 (en) * | 2016-08-25 | 2018-03-01 | The Regents Of The University Of Michigan | Inhibitors of-bcr-abl mutants and use thereof |
CN106748991B (zh) * | 2016-11-14 | 2020-03-17 | 西安交通大学 | 一种具有抗肿瘤活性的双芳基脲化合物及其制备方法和应用 |
CN106748990A (zh) * | 2016-11-14 | 2017-05-31 | 西安交通大学 | 一种具有抗肿瘤活性的双芳基脲类化合物及其制备方法和应用 |
CN106748989B (zh) * | 2016-11-14 | 2020-03-17 | 西安交通大学 | 一种具有抗肿瘤活性的二芳基脲类化合物及其制备方法和应用 |
WO2018141642A1 (en) * | 2017-02-06 | 2018-08-09 | BASF Agro B.V. | Process for the preparation of 2-chloro-4-fluoro-5-nitrobenzotrichloride |
JP7341060B2 (ja) | 2017-02-10 | 2023-09-08 | アンスティチュ ナショナル ドゥ ラ サンテ エ ドゥ ラ ルシェルシュ メディカル | Mapk経路の活性化に関連付けられる癌の処置のための方法及び医薬組成物 |
WO2019071147A1 (en) | 2017-10-05 | 2019-04-11 | Fulcrum Therapeutics, Inc. | INHIBITORS OF KINASE P38 REDUCING EXPRESSION OF DUX4 GENE AND DOWNSTREAM GENES FOR THE TREATMENT OF FSHD |
US10342786B2 (en) | 2017-10-05 | 2019-07-09 | Fulcrum Therapeutics, Inc. | P38 kinase inhibitors reduce DUX4 and downstream gene expression for the treatment of FSHD |
WO2019133810A1 (en) | 2017-12-28 | 2019-07-04 | Tract Pharmaceuticals, Inc. | Stem cell culture systems for columnar epithelial stem cells, and uses related thereto |
CN113264874A (zh) * | 2021-05-21 | 2021-08-17 | 华东理工大学 | 一种取代的二芳基脲衍生物及其制备方法和应用 |
CN113603616B (zh) * | 2021-07-05 | 2023-03-07 | 安徽医科大学 | 一种丹皮酚衍生物及其制备方法、制剂与应用 |
WO2023222332A1 (en) * | 2022-05-16 | 2023-11-23 | Merck Patent Gmbh | Diphenyl ureas for the treatment of viral infections |
Family Cites Families (11)
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US4191767A (en) * | 1977-01-07 | 1980-03-04 | Westwood Pharmaceuticals, Inc. | Method for treating fungal infection in mammals with imidazo [1,2-a]quinoxalines |
EP1041982B1 (en) * | 1997-12-22 | 2011-10-19 | Bayer HealthCare LLC | INHIBITION OF p38 KINASE ACTIVITY USING SUBSTITUTED HETEROCYCLIC UREAS |
ES2153809T3 (es) * | 1997-12-22 | 2005-07-16 | Bayer Pharmaceuticals Corporation | Inhibicion de la cinasa raf por uso de difnil-ureas sustituidas simetrica y asimetricamente. |
JP3887769B2 (ja) * | 1997-12-22 | 2007-02-28 | バイエル コーポレイション | 対称および非対称ジフェニル尿素を用いるp38キナーゼの阻害 |
ATE556713T1 (de) * | 1999-01-13 | 2012-05-15 | Bayer Healthcare Llc | Omega-carboxyarylsubstituierte-diphenyl- harnstoffe als p38-kinasehemmer |
CZ299125B6 (cs) * | 1999-01-13 | 2008-04-30 | Bayer Corporation | Difenylové mocoviny substituované omega-karboxyarylovou skupinou jako inhibitory rafkinázy, jejich použití a farmaceutické kompozice s jejich obsahem |
MXPA02004594A (es) * | 1999-11-16 | 2002-10-23 | Boehringer Ingelheim Pharma | Derivados de urea como agentes anti-inflamatorios. |
US7235576B1 (en) * | 2001-01-12 | 2007-06-26 | Bayer Pharmaceuticals Corporation | Omega-carboxyaryl substituted diphenyl ureas as raf kinase inhibitors |
AU2003209116A1 (en) * | 2002-02-11 | 2003-09-04 | Bayer Pharmaceuticals Corporation | Aryl ureas with angiogenesis inhibiting activity |
ATE529406T1 (de) * | 2002-02-11 | 2011-11-15 | Bayer Healthcare Llc | Aryl-harnstoffe als kinase inhibitoren |
TW200406374A (en) * | 2002-05-29 | 2004-05-01 | Novartis Ag | Diaryl urea derivatives useful for the treatment of protein kinase dependent diseases |
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BRPI0507198A (pt) | 2007-06-26 |
EP1730111A2 (en) | 2006-12-13 |
JP2007519653A (ja) | 2007-07-19 |
WO2005075425A2 (en) | 2005-08-18 |
RU2006131045A (ru) | 2008-03-10 |
US20070161677A1 (en) | 2007-07-12 |
CA2554878A1 (en) | 2005-08-18 |
KR20060132882A (ko) | 2006-12-22 |
AR047585A1 (es) | 2006-01-25 |
AU2005211448A1 (en) | 2005-08-18 |
CN1972925A (zh) | 2007-05-30 |
WO2005075425A3 (en) | 2006-12-14 |
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