ES2155045T3 - Inhibicion de la quinasa raf utilizando ureas heterociclicas sustituidas con arilo y heteroarilo. - Google Patents
Inhibicion de la quinasa raf utilizando ureas heterociclicas sustituidas con arilo y heteroarilo. Download PDFInfo
- Publication number
- ES2155045T3 ES2155045T3 ES98963810T ES98963810T ES2155045T3 ES 2155045 T3 ES2155045 T3 ES 2155045T3 ES 98963810 T ES98963810 T ES 98963810T ES 98963810 T ES98963810 T ES 98963810T ES 2155045 T3 ES2155045 T3 ES 2155045T3
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- Spain
- Prior art keywords
- substituted
- group
- alkyl
- heteroaryl
- per
- 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
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- 230000005764 inhibitory process Effects 0.000 title claims description 9
- 150000003672 ureas Chemical class 0.000 title description 11
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 95
- 150000001875 compounds Chemical class 0.000 claims abstract description 78
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 67
- 125000001072 heteroaryl group Chemical group 0.000 claims abstract description 50
- 125000003118 aryl group Chemical group 0.000 claims abstract description 49
- 125000001424 substituent group Chemical group 0.000 claims abstract description 46
- 150000002367 halogens Chemical class 0.000 claims abstract description 45
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims abstract description 36
- 125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 33
- 125000005843 halogen group Chemical group 0.000 claims abstract description 31
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 21
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 17
- 229910052717 sulfur Inorganic materials 0.000 claims abstract description 15
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims abstract description 14
- 239000001301 oxygen Substances 0.000 claims abstract description 14
- 150000003839 salts Chemical class 0.000 claims abstract description 14
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims abstract description 12
- 239000011593 sulfur Substances 0.000 claims abstract description 12
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 11
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 9
- 125000005346 substituted cycloalkyl group Chemical group 0.000 claims abstract description 3
- 125000005915 C6-C14 aryl group Chemical group 0.000 claims abstract 8
- 125000006374 C2-C10 alkenyl group Chemical group 0.000 claims abstract 7
- 125000000027 (C1-C10) alkoxy group Chemical group 0.000 claims abstract 6
- -1 5-imidazolyl Chemical group 0.000 claims description 100
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 52
- 125000002877 alkyl aryl group Chemical group 0.000 claims description 36
- 125000004076 pyridyl group Chemical group 0.000 claims description 31
- 239000007787 solid Substances 0.000 claims description 27
- 206010028980 Neoplasm Diseases 0.000 claims description 20
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims description 19
- 125000003342 alkenyl group Chemical group 0.000 claims description 17
- 238000011282 treatment Methods 0.000 claims description 17
- 108010077182 raf Kinases Proteins 0.000 claims description 15
- 102000009929 raf Kinases Human genes 0.000 claims description 15
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 12
- 108091000080 Phosphotransferase Proteins 0.000 claims description 10
- 239000004202 carbamide Substances 0.000 claims description 10
- 230000001404 mediated effect Effects 0.000 claims description 10
- 102000020233 phosphotransferase Human genes 0.000 claims description 10
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 9
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 claims description 8
- 125000003545 alkoxy group Chemical group 0.000 claims description 8
- 201000011510 cancer Diseases 0.000 claims description 8
- 229910052799 carbon Inorganic materials 0.000 claims description 8
- USIUVYZYUHIAEV-UHFFFAOYSA-N diphenyl ether Chemical group C=1C=CC=CC=1OC1=CC=CC=C1 USIUVYZYUHIAEV-UHFFFAOYSA-N 0.000 claims description 8
- 229910052739 hydrogen Inorganic materials 0.000 claims description 8
- AWJUIBRHMBBTKR-UHFFFAOYSA-N isoquinoline Chemical compound C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 claims description 8
- 108010014186 ras Proteins Proteins 0.000 claims description 8
- 102000016914 ras Proteins Human genes 0.000 claims description 8
- 239000003814 drug Substances 0.000 claims description 7
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 7
- 238000002360 preparation method Methods 0.000 claims description 7
- 125000003107 substituted aryl group Chemical group 0.000 claims description 7
- 229910052801 chlorine Inorganic materials 0.000 claims description 6
- DMBHHRLKUKUOEG-UHFFFAOYSA-N diphenylamine Chemical group C=1C=CC=CC=1NC1=CC=CC=C1 DMBHHRLKUKUOEG-UHFFFAOYSA-N 0.000 claims description 6
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 6
- 229910052731 fluorine Inorganic materials 0.000 claims description 6
- 239000001257 hydrogen Substances 0.000 claims description 6
- 239000008194 pharmaceutical composition Substances 0.000 claims description 6
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 claims description 5
- 125000001624 naphthyl group Chemical group 0.000 claims description 5
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 5
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 5
- MEAAWTRWNWSLPF-UHFFFAOYSA-N 2-phenoxypyridine Chemical group C=1C=CC=NC=1OC1=CC=CC=C1 MEAAWTRWNWSLPF-UHFFFAOYSA-N 0.000 claims description 4
- LTYMSROWYAPPGB-UHFFFAOYSA-N diphenyl sulfide Chemical group C=1C=CC=CC=1SC1=CC=CC=C1 LTYMSROWYAPPGB-UHFFFAOYSA-N 0.000 claims description 4
- 201000010099 disease Diseases 0.000 claims description 4
- 238000000338 in vitro Methods 0.000 claims description 4
- 230000019491 signal transduction Effects 0.000 claims description 4
- DABOOAVTBIRGHP-UHFFFAOYSA-N 1-phenoxynaphthalene Chemical compound C=1C=CC2=CC=CC=C2C=1OC1=CC=CC=C1 DABOOAVTBIRGHP-UHFFFAOYSA-N 0.000 claims description 3
- DWBYVHWWZMMIOT-UHFFFAOYSA-N 2-phenylsulfanylpyridine Chemical group C=1C=CC=NC=1SC1=CC=CC=C1 DWBYVHWWZMMIOT-UHFFFAOYSA-N 0.000 claims description 3
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 claims description 3
- 125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 claims description 3
- CWDWFSXUQODZGW-UHFFFAOYSA-N 5-thiazolyl Chemical group [C]1=CN=CS1 CWDWFSXUQODZGW-UHFFFAOYSA-N 0.000 claims description 3
- 230000001419 dependent effect Effects 0.000 claims description 3
- 229940035422 diphenylamine Drugs 0.000 claims description 3
- 125000003373 pyrazinyl group Chemical group 0.000 claims description 3
- FFIUOTRLUBELIM-UHFFFAOYSA-N 1-(5-tert-butyl-2-phenylpyrazol-3-yl)-3-[4-(pyridin-4-ylmethyl)phenyl]urea Chemical compound C=1C=CC=CC=1N1N=C(C(C)(C)C)C=C1NC(=O)NC(C=C1)=CC=C1CC1=CC=NC=C1 FFIUOTRLUBELIM-UHFFFAOYSA-N 0.000 claims description 2
- WJSPIIPLHMHWBE-UHFFFAOYSA-N 1-(5-tert-butyl-2-pyridin-4-ylfuran-3-yl)-3-(2,3-dichlorophenyl)urea Chemical compound C=1C=NC=CC=1C=1OC(C(C)(C)C)=CC=1NC(=O)NC1=CC=CC(Cl)=C1Cl WJSPIIPLHMHWBE-UHFFFAOYSA-N 0.000 claims description 2
- CUYZHKUAFIPCSJ-UHFFFAOYSA-N 1-[2-(3-aminophenyl)-5-tert-butylpyrazol-3-yl]-3-(4-phenoxyphenyl)urea Chemical compound C=1C=CC(N)=CC=1N1N=C(C(C)(C)C)C=C1NC(=O)NC(C=C1)=CC=C1OC1=CC=CC=C1 CUYZHKUAFIPCSJ-UHFFFAOYSA-N 0.000 claims description 2
- WJOFCYKMTBWGDE-UHFFFAOYSA-N 1-[2-(3-aminophenyl)-5-tert-butylpyrazol-3-yl]-3-(4-pyridin-4-ylsulfanylphenyl)urea Chemical compound C=1C=CC(N)=CC=1N1N=C(C(C)(C)C)C=C1NC(=O)NC(C=C1)=CC=C1SC1=CC=NC=C1 WJOFCYKMTBWGDE-UHFFFAOYSA-N 0.000 claims description 2
- MTDBGUSQNDHXBI-UHFFFAOYSA-N 1-[5-tert-butyl-2-(4-methoxyphenyl)pyrazol-3-yl]-3-(2,3-dichlorophenyl)urea Chemical compound C1=CC(OC)=CC=C1N1C(NC(=O)NC=2C(=C(Cl)C=CC=2)Cl)=CC(C(C)(C)C)=N1 MTDBGUSQNDHXBI-UHFFFAOYSA-N 0.000 claims description 2
- 125000001462 1-pyrrolyl group Chemical group [*]N1C([H])=C([H])C([H])=C1[H] 0.000 claims description 2
- 125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 claims description 2
- CEBDRQUBQYQBEV-UHFFFAOYSA-N 2-phenoxypyrimidine Chemical group N=1C=CC=NC=1OC1=CC=CC=C1 CEBDRQUBQYQBEV-UHFFFAOYSA-N 0.000 claims description 2
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 2
- 125000000389 2-pyrrolyl group Chemical group [H]N1C([*])=C([H])C([H])=C1[H] 0.000 claims description 2
- 125000003682 3-furyl group Chemical group O1C([H])=C([*])C([H])=C1[H] 0.000 claims description 2
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 2
- 125000001397 3-pyrrolyl group Chemical group [H]N1C([H])=C([*])C([H])=C1[H] 0.000 claims description 2
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 2
- KDDQRKBRJSGMQE-UHFFFAOYSA-N 4-thiazolyl Chemical compound [C]1=CSC=N1 KDDQRKBRJSGMQE-UHFFFAOYSA-N 0.000 claims description 2
- 208000003200 Adenoma Diseases 0.000 claims description 2
- FSEXLNMNADBYJU-UHFFFAOYSA-N alpha-Phenylquinoline Natural products C1=CC=CC=C1C1=CC=C(C=CC=C2)C2=N1 FSEXLNMNADBYJU-UHFFFAOYSA-N 0.000 claims description 2
- 210000001072 colon Anatomy 0.000 claims description 2
- 238000000021 kinase assay Methods 0.000 claims description 2
- FEBHBMHAIORKEA-UHFFFAOYSA-N n-[3-[3-tert-butyl-5-[(4-phenoxyphenyl)carbamoylamino]pyrazol-1-yl]phenyl]acetamide Chemical compound CC(=O)NC1=CC=CC(N2C(=CC(=N2)C(C)(C)C)NC(=O)NC=2C=CC(OC=3C=CC=CC=3)=CC=2)=C1 FEBHBMHAIORKEA-UHFFFAOYSA-N 0.000 claims description 2
- 210000000496 pancreas Anatomy 0.000 claims description 2
- 125000002206 pyridazin-3-yl group Chemical group [H]C1=C([H])C([H])=C(*)N=N1 0.000 claims description 2
- 125000004940 pyridazin-4-yl group Chemical group N1=NC=C(C=C1)* 0.000 claims description 2
- 125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 claims description 2
- 125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 claims description 2
- 125000004528 pyrimidin-5-yl group Chemical group N1=CN=CC(=C1)* 0.000 claims description 2
- 125000004943 pyrimidin-6-yl group Chemical group N1=CN=CC=C1* 0.000 claims description 2
- 125000004434 sulfur atom Chemical group 0.000 claims description 2
- 210000001685 thyroid gland Anatomy 0.000 claims description 2
- 210000003932 urinary bladder Anatomy 0.000 claims description 2
- 125000005213 alkyl heteroaryl group Chemical group 0.000 claims 3
- WWASAISHUBOFAR-UHFFFAOYSA-N 2-[1-(2-pyridin-2-ylnaphthalen-1-yl)sulfanylnaphthalen-2-yl]pyridine Chemical compound C=1C=CC=NC=1C=1C=CC2=CC=CC=C2C=1SC(C1=CC=CC=C1C=C1)=C1C1=CC=CC=N1 WWASAISHUBOFAR-UHFFFAOYSA-N 0.000 claims 2
- 125000002619 bicyclic group Chemical group 0.000 claims 2
- SNOOUWRIMMFWNE-UHFFFAOYSA-M sodium;6-[(3,4,5-trimethoxybenzoyl)amino]hexanoate Chemical compound [Na+].COC1=CC(C(=O)NCCCCCC([O-])=O)=CC(OC)=C1OC SNOOUWRIMMFWNE-UHFFFAOYSA-M 0.000 claims 2
- ZFJZXGAFKPFNSG-UHFFFAOYSA-N 1-(5-tert-butyl-2-phenylpyrazol-3-yl)-3-(2,3-dichlorophenyl)urea Chemical compound C=1C=CC=CC=1N1N=C(C(C)(C)C)C=C1NC(=O)NC1=CC=CC(Cl)=C1Cl ZFJZXGAFKPFNSG-UHFFFAOYSA-N 0.000 claims 1
- RCZQFYZVLCMFFN-UHFFFAOYSA-N 1-(5-tert-butyl-2-phenylpyrazol-3-yl)-3-(2,4-difluorophenyl)urea Chemical compound C=1C=CC=CC=1N1N=C(C(C)(C)C)C=C1NC(=O)NC1=CC=C(F)C=C1F RCZQFYZVLCMFFN-UHFFFAOYSA-N 0.000 claims 1
- UUUIRYMTQKTIML-UHFFFAOYSA-N 1-(5-tert-butyl-2-phenylpyrazol-3-yl)-3-(3-cyanophenyl)urea Chemical compound C=1C=CC=CC=1N1N=C(C(C)(C)C)C=C1NC(=O)NC1=CC=CC(C#N)=C1 UUUIRYMTQKTIML-UHFFFAOYSA-N 0.000 claims 1
- TYQAQAZCZRPYRN-UHFFFAOYSA-N 1-(5-tert-butyl-2-phenylpyrazol-3-yl)-3-(3-fluorophenyl)urea Chemical compound C=1C=CC=CC=1N1N=C(C(C)(C)C)C=C1NC(=O)NC1=CC=CC(F)=C1 TYQAQAZCZRPYRN-UHFFFAOYSA-N 0.000 claims 1
- IQRRXNHDVPPLBU-UHFFFAOYSA-N 1-(5-tert-butyl-2-phenylpyrazol-3-yl)-3-(4-nitrophenyl)urea Chemical compound C=1C=CC=CC=1N1N=C(C(C)(C)C)C=C1NC(=O)NC1=CC=C([N+]([O-])=O)C=C1 IQRRXNHDVPPLBU-UHFFFAOYSA-N 0.000 claims 1
- GDPHSKJEYFGMHV-UHFFFAOYSA-N 1-(5-tert-butyl-2-phenylthiophen-3-yl)-3-(2,3-dichlorophenyl)urea Chemical compound C=1C=CC=CC=1C=1SC(C(C)(C)C)=CC=1NC(=O)NC1=CC=CC(Cl)=C1Cl GDPHSKJEYFGMHV-UHFFFAOYSA-N 0.000 claims 1
- HSQBWWZLDMOFSS-UHFFFAOYSA-N 1-(5-tert-butyl-2-pyridin-2-ylpyrazol-3-yl)-3-(2,3-dichlorophenyl)urea Chemical compound C=1C=CC=NC=1N1N=C(C(C)(C)C)C=C1NC(=O)NC1=CC=CC(Cl)=C1Cl HSQBWWZLDMOFSS-UHFFFAOYSA-N 0.000 claims 1
- JHVUVPPREJEJFT-UHFFFAOYSA-N 1-(5-tert-butyl-2-pyridin-4-ylpyrazol-3-yl)-3-[4-(pyridin-4-ylmethyl)phenyl]urea Chemical compound C=1C=NC=CC=1N1N=C(C(C)(C)C)C=C1NC(=O)NC(C=C1)=CC=C1CC1=CC=NC=C1 JHVUVPPREJEJFT-UHFFFAOYSA-N 0.000 claims 1
- LDXAGTHPWDVZFU-UHFFFAOYSA-N 1-[2-(3-aminophenyl)-5-tert-butylpyrazol-3-yl]-3-(2,3-dichlorophenyl)urea Chemical compound C=1C=CC(N)=CC=1N1N=C(C(C)(C)C)C=C1NC(=O)NC1=CC=CC(Cl)=C1Cl LDXAGTHPWDVZFU-UHFFFAOYSA-N 0.000 claims 1
- VQFFXUJUGHSTCN-UHFFFAOYSA-N 1-[2-(3-aminophenyl)-5-tert-butylpyrazol-3-yl]-3-[4-(pyridin-4-ylmethyl)phenyl]urea Chemical compound C=1C=CC(N)=CC=1N1N=C(C(C)(C)C)C=C1NC(=O)NC(C=C1)=CC=C1CC1=CC=NC=C1 VQFFXUJUGHSTCN-UHFFFAOYSA-N 0.000 claims 1
- SMIBCPFPBUZPDB-UHFFFAOYSA-N 1-[2-(4-aminophenyl)-5-tert-butylpyrazol-3-yl]-3-(2,3-dichlorophenyl)urea Chemical compound C=1C=C(N)C=CC=1N1N=C(C(C)(C)C)C=C1NC(=O)NC1=CC=CC(Cl)=C1Cl SMIBCPFPBUZPDB-UHFFFAOYSA-N 0.000 claims 1
- NZXFWWIIOCLRBG-UHFFFAOYSA-N 1-[5-tert-butyl-2-(2,5-dichlorophenyl)pyrazol-3-yl]-3-[4-(pyridin-4-ylmethyl)phenyl]urea Chemical compound C=1C(Cl)=CC=C(Cl)C=1N1N=C(C(C)(C)C)C=C1NC(=O)NC(C=C1)=CC=C1CC1=CC=NC=C1 NZXFWWIIOCLRBG-UHFFFAOYSA-N 0.000 claims 1
- HCXKSJKYSGOXPC-UHFFFAOYSA-N 1-[5-tert-butyl-2-(2-methylphenyl)pyrazol-3-yl]-3-(2,3-dichlorophenyl)urea Chemical compound CC1=CC=CC=C1N1C(NC(=O)NC=2C(=C(Cl)C=CC=2)Cl)=CC(C(C)(C)C)=N1 HCXKSJKYSGOXPC-UHFFFAOYSA-N 0.000 claims 1
- IIJPXSBAILRPBH-UHFFFAOYSA-N 1-[5-tert-butyl-2-(2-methylphenyl)pyrazol-3-yl]-3-[4-(pyridin-4-ylmethyl)phenyl]urea Chemical compound CC1=CC=CC=C1N1C(NC(=O)NC=2C=CC(CC=3C=CN=CC=3)=CC=2)=CC(C(C)(C)C)=N1 IIJPXSBAILRPBH-UHFFFAOYSA-N 0.000 claims 1
- WUSBLDMZPYBKMT-UHFFFAOYSA-N 1-[5-tert-butyl-2-(3-fluorophenyl)pyrazol-3-yl]-3-(2,3-dichlorophenyl)urea Chemical compound C=1C=CC(F)=CC=1N1N=C(C(C)(C)C)C=C1NC(=O)NC1=CC=CC(Cl)=C1Cl WUSBLDMZPYBKMT-UHFFFAOYSA-N 0.000 claims 1
- ZUMZFZPWNCSPCR-UHFFFAOYSA-N 1-[5-tert-butyl-2-(3-fluorophenyl)pyrazol-3-yl]-3-[4-(pyridin-4-ylmethyl)phenyl]urea Chemical compound C=1C=CC(F)=CC=1N1N=C(C(C)(C)C)C=C1NC(=O)NC(C=C1)=CC=C1CC1=CC=NC=C1 ZUMZFZPWNCSPCR-UHFFFAOYSA-N 0.000 claims 1
- PRKGLTOOEULMFS-UHFFFAOYSA-N 1-[5-tert-butyl-2-(3-methoxyphenyl)pyrazol-3-yl]-3-(2,3-dichlorophenyl)urea Chemical compound COC1=CC=CC(N2C(=CC(=N2)C(C)(C)C)NC(=O)NC=2C(=C(Cl)C=CC=2)Cl)=C1 PRKGLTOOEULMFS-UHFFFAOYSA-N 0.000 claims 1
- DHHUPNJXRLHQNZ-UHFFFAOYSA-N 1-[5-tert-butyl-2-(3-methoxyphenyl)pyrazol-3-yl]-3-[4-(pyridin-4-ylmethyl)phenyl]urea Chemical compound COC1=CC=CC(N2C(=CC(=N2)C(C)(C)C)NC(=O)NC=2C=CC(CC=3C=CN=CC=3)=CC=2)=C1 DHHUPNJXRLHQNZ-UHFFFAOYSA-N 0.000 claims 1
- KXQRNZIJVGMDMI-UHFFFAOYSA-N 1-[5-tert-butyl-2-(3-nitrophenyl)pyrazol-3-yl]-3-(2,3-dichlorophenyl)urea Chemical compound C=1C=CC([N+]([O-])=O)=CC=1N1N=C(C(C)(C)C)C=C1NC(=O)NC1=CC=CC(Cl)=C1Cl KXQRNZIJVGMDMI-UHFFFAOYSA-N 0.000 claims 1
- YQDHLCOTFVFZSP-UHFFFAOYSA-N 1-[5-tert-butyl-2-(3-nitrophenyl)pyrazol-3-yl]-3-(4-phenoxyphenyl)urea Chemical compound C=1C=CC([N+]([O-])=O)=CC=1N1N=C(C(C)(C)C)C=C1NC(=O)NC(C=C1)=CC=C1OC1=CC=CC=C1 YQDHLCOTFVFZSP-UHFFFAOYSA-N 0.000 claims 1
- JPLSXEUUQPVZGF-UHFFFAOYSA-N 1-[5-tert-butyl-2-(3-nitrophenyl)pyrazol-3-yl]-3-(4-pyridin-4-ylsulfanylphenyl)urea Chemical compound C=1C=CC([N+]([O-])=O)=CC=1N1N=C(C(C)(C)C)C=C1NC(=O)NC(C=C1)=CC=C1SC1=CC=NC=C1 JPLSXEUUQPVZGF-UHFFFAOYSA-N 0.000 claims 1
- XIRCPVFPYLPUAD-UHFFFAOYSA-N 1-[5-tert-butyl-2-(3-nitrophenyl)pyrazol-3-yl]-3-[4-(pyridin-4-ylmethyl)phenyl]urea Chemical compound C=1C=CC([N+]([O-])=O)=CC=1N1N=C(C(C)(C)C)C=C1NC(=O)NC(C=C1)=CC=C1CC1=CC=NC=C1 XIRCPVFPYLPUAD-UHFFFAOYSA-N 0.000 claims 1
- WWWFKRCQKBNBSM-UHFFFAOYSA-N 1-[5-tert-butyl-2-(4-chlorophenyl)pyrazol-3-yl]-3-(2,3-dichlorophenyl)urea Chemical compound C=1C=C(Cl)C=CC=1N1N=C(C(C)(C)C)C=C1NC(=O)NC1=CC=CC(Cl)=C1Cl WWWFKRCQKBNBSM-UHFFFAOYSA-N 0.000 claims 1
- TUOYWZHLTSNOHS-UHFFFAOYSA-N 1-[5-tert-butyl-2-(4-fluorophenyl)pyrazol-3-yl]-3-[4-(pyridin-4-ylmethyl)phenyl]urea Chemical compound C=1C=C(F)C=CC=1N1N=C(C(C)(C)C)C=C1NC(=O)NC(C=C1)=CC=C1CC1=CC=NC=C1 TUOYWZHLTSNOHS-UHFFFAOYSA-N 0.000 claims 1
- MTXYPFKQMNXTQA-UHFFFAOYSA-N 1-[5-tert-butyl-2-(4-nitrophenyl)pyrazol-3-yl]-3-(2,3-dichlorophenyl)urea Chemical compound C=1C=C([N+]([O-])=O)C=CC=1N1N=C(C(C)(C)C)C=C1NC(=O)NC1=CC=CC(Cl)=C1Cl MTXYPFKQMNXTQA-UHFFFAOYSA-N 0.000 claims 1
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/415—1,2-Diazoles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- 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
- C07D213/04—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
- C07D213/72—Nitrogen atoms
- C07D213/76—Nitrogen atoms to which a second hetero atom is attached
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/14—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members 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
- C07D231/38—Nitrogen atoms
- C07D231/40—Acylated on said nitrogen atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D239/32—One oxygen, sulfur or nitrogen atom
- C07D239/42—One nitrogen atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
- C07D333/26—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur 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
- C07D333/30—Hetero atoms other than halogen
- C07D333/36—Nitrogen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/04—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
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- Chemical & Material Sciences (AREA)
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- Animal Behavior & Ethology (AREA)
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- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
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- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Pyridine Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Heterocyclic Compounds Containing Sulfur Atoms (AREA)
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Applications Claiming Priority (2)
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US99618197A | 1997-12-22 | 1997-12-22 | |
US996181 | 1997-12-22 |
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ES98963810T Expired - Lifetime ES2155045T3 (es) | 1997-12-22 | 1998-12-22 | Inhibicion de la quinasa raf utilizando ureas heterociclicas sustituidas con arilo y heteroarilo. |
Country Status (29)
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DE1043995T1 (de) * | 1997-12-22 | 2001-06-07 | Bayer Corp., Pittsburgh | INHIBIERUNG DER p38 KINASE-AKTIVITÄT DURCH DIE VERWENDUNG VON ARYL- UND HETEROARYLSUBSTITUIERTEN HARNSTOFFEN |
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- 1998-12-22 AU AU19055/99A patent/AU765412B2/en not_active Ceased
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- 1998-12-22 RU RU2000120162/04A patent/RU2265597C2/ru not_active IP Right Cessation
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- 1998-12-22 DK DK98963810T patent/DK1056725T3/da active
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- 1998-12-22 HU HU0004426A patent/HUP0004426A3/hu unknown
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- 1998-12-22 TR TR2001/00918T patent/TR200100918T2/xx unknown
- 1998-12-22 PT PT98963810T patent/PT1056725E/pt unknown
- 1998-12-22 CZ CZ20002349A patent/CZ299836B6/cs not_active IP Right Cessation
- 1998-12-22 BR BR9814361-1A patent/BR9814361A/pt not_active IP Right Cessation
- 1998-12-22 DE DE1056725T patent/DE1056725T1/de active Pending
- 1998-12-22 PL PL98341356A patent/PL341356A1/xx not_active Application Discontinuation
- 1998-12-22 DE DE69834842T patent/DE69834842T2/de not_active Expired - Lifetime
- 1998-12-22 WO PCT/US1998/026082 patent/WO1999032455A1/en active IP Right Grant
- 1998-12-22 NZ NZ505845A patent/NZ505845A/en not_active IP Right Cessation
- 1998-12-22 ES ES98963810T patent/ES2155045T3/es not_active Expired - Lifetime
- 1998-12-22 CA CA2315713A patent/CA2315713C/en not_active Expired - Fee Related
- 1998-12-22 TR TR2000/02617T patent/TR200002617T2/xx unknown
- 1998-12-22 ID IDW20001417A patent/ID26328A/id unknown
- 1998-12-22 AT AT98963810T patent/ATE328873T1/de active
- 1998-12-22 KR KR1020007007014A patent/KR100622138B1/ko not_active IP Right Cessation
- 1998-12-22 IL IL13677398A patent/IL136773A0/xx active IP Right Grant
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2000
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2001
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2006
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