NO326325B1 - Kinolin- og kinazolinderivater med azolylgruppe - Google Patents
Kinolin- og kinazolinderivater med azolylgruppe Download PDFInfo
- Publication number
- NO326325B1 NO326325B1 NO20034595A NO20034595A NO326325B1 NO 326325 B1 NO326325 B1 NO 326325B1 NO 20034595 A NO20034595 A NO 20034595A NO 20034595 A NO20034595 A NO 20034595A NO 326325 B1 NO326325 B1 NO 326325B1
- Authority
- NO
- Norway
- Prior art keywords
- dimethoxy
- urea
- oxy
- quinolyl
- chloroform
- Prior art date
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- 125000003943 azolyl group Chemical group 0.000 title claims abstract description 10
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 title 2
- 125000002294 quinazolinyl group Chemical class N1=C(N=CC2=CC=CC=C12)* 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 203
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 25
- 150000003839 salts Chemical class 0.000 claims abstract description 17
- 239000012453 solvate Substances 0.000 claims abstract description 11
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 586
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims description 146
- 239000004202 carbamide Substances 0.000 claims description 97
- -1 6,7-di-methoxy-4-quinolyl Chemical group 0.000 claims description 61
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 45
- 206010028980 Neoplasm Diseases 0.000 claims description 33
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 32
- 125000005843 halogen group Chemical group 0.000 claims description 23
- 201000010099 disease Diseases 0.000 claims description 16
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 16
- 239000003814 drug Substances 0.000 claims description 13
- 239000000463 material Substances 0.000 claims description 13
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 13
- 206010003210 Arteriosclerosis Diseases 0.000 claims description 11
- 206010012689 Diabetic retinopathy Diseases 0.000 claims description 11
- 208000007766 Kaposi sarcoma Diseases 0.000 claims description 11
- 201000004681 Psoriasis Diseases 0.000 claims description 11
- 208000011775 arteriosclerosis disease Diseases 0.000 claims description 11
- 230000001684 chronic effect Effects 0.000 claims description 11
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 8
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 7
- 206010008583 Chloroma Diseases 0.000 claims description 7
- 229910052731 fluorine Inorganic materials 0.000 claims description 7
- 238000002360 preparation method Methods 0.000 claims description 7
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 claims description 6
- 210000004204 blood vessel Anatomy 0.000 claims description 6
- 229910052801 chlorine Inorganic materials 0.000 claims description 6
- 239000000460 chlorine Substances 0.000 claims description 6
- 125000001153 fluoro group Chemical group F* 0.000 claims description 6
- 230000002401 inhibitory effect Effects 0.000 claims description 6
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 5
- 239000004480 active ingredient Substances 0.000 claims description 5
- 230000033115 angiogenesis Effects 0.000 claims description 5
- 125000004916 (C1-C6) alkylcarbonyl group Chemical group 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 4
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 4
- 125000000335 thiazolyl group Chemical group 0.000 claims description 4
- 125000004520 1,3,4-thiadiazolyl group Chemical group 0.000 claims description 3
- 125000004448 alkyl carbonyl group Chemical group 0.000 claims description 3
- 125000000842 isoxazolyl group Chemical group 0.000 claims description 3
- 125000006700 (C1-C6) alkylthio group Chemical group 0.000 claims description 2
- QDFULLPLTAUYQC-UHFFFAOYSA-N 1-[3-chloro-4-(6,7-dimethoxyquinolin-4-yl)oxyphenyl]-3-(1,2-oxazol-3-yl)urea Chemical compound C=12C=C(OC)C(OC)=CC2=NC=CC=1OC(C(=C1)Cl)=CC=C1NC(=O)NC=1C=CON=1 QDFULLPLTAUYQC-UHFFFAOYSA-N 0.000 claims description 2
- WZQWWYKNLMNLRV-UHFFFAOYSA-N 1-[3-chloro-4-(6,7-dimethoxyquinolin-4-yl)oxyphenyl]-3-(1h-pyrazol-5-yl)urea Chemical compound C=12C=C(OC)C(OC)=CC2=NC=CC=1OC(C(=C1)Cl)=CC=C1NC(=O)NC1=CC=NN1 WZQWWYKNLMNLRV-UHFFFAOYSA-N 0.000 claims description 2
- RFFQHLJFGSULAP-UHFFFAOYSA-N 1-[4-(6,7-dimethoxyquinazolin-4-yl)oxyphenyl]-3-(5-methyl-1,2-oxazol-3-yl)urea Chemical compound C=12C=C(OC)C(OC)=CC2=NC=NC=1OC(C=C1)=CC=C1NC(=O)NC=1C=C(C)ON=1 RFFQHLJFGSULAP-UHFFFAOYSA-N 0.000 claims description 2
- SPHDXDDNGFAWGX-UHFFFAOYSA-N 1-[4-(6,7-dimethoxyquinolin-4-yl)oxy-2-fluorophenyl]-3-(1h-pyrazol-5-yl)urea Chemical compound C=12C=C(OC)C(OC)=CC2=NC=CC=1OC(C=C1F)=CC=C1NC(=O)NC1=CC=NN1 SPHDXDDNGFAWGX-UHFFFAOYSA-N 0.000 claims description 2
- HIZWPISQYHTLLO-UHFFFAOYSA-N 1-[4-(6,7-dimethoxyquinolin-4-yl)oxy-2-fluorophenyl]-3-(5-methyl-1,3-thiazol-2-yl)urea;hydrochloride Chemical compound Cl.C=12C=C(OC)C(OC)=CC2=NC=CC=1OC(C=C1F)=CC=C1NC(=O)NC1=NC=C(C)S1 HIZWPISQYHTLLO-UHFFFAOYSA-N 0.000 claims description 2
- 125000004414 alkyl thio group Chemical group 0.000 claims description 2
- 229940124597 therapeutic agent Drugs 0.000 claims description 2
- YWQPSGHSYQEWDD-UHFFFAOYSA-N 1-(4-tert-butyl-1,3-thiazol-2-yl)-3-[2-chloro-4-(6,7-dimethoxyquinolin-4-yl)oxyphenyl]urea Chemical compound C=12C=C(OC)C(OC)=CC2=NC=CC=1OC(C=C1Cl)=CC=C1NC(=O)NC1=NC(C(C)(C)C)=CS1 YWQPSGHSYQEWDD-UHFFFAOYSA-N 0.000 claims 1
- DCPOYTINCWABPJ-UHFFFAOYSA-N 1-[2-chloro-4-(6,7-dimethoxyquinazolin-4-yl)oxyphenyl]-3-(5-methyl-1,2-oxazol-3-yl)urea Chemical compound C=12C=C(OC)C(OC)=CC2=NC=NC=1OC(C=C1Cl)=CC=C1NC(=O)NC=1C=C(C)ON=1 DCPOYTINCWABPJ-UHFFFAOYSA-N 0.000 claims 1
- FGBHKOGVQIRXKD-UHFFFAOYSA-N 1-[2-chloro-4-(6,7-dimethoxyquinolin-4-yl)oxyphenyl]-3-(4-methyl-1,3-thiazol-2-yl)urea Chemical compound C=12C=C(OC)C(OC)=CC2=NC=CC=1OC(C=C1Cl)=CC=C1NC(=O)NC1=NC(C)=CS1 FGBHKOGVQIRXKD-UHFFFAOYSA-N 0.000 claims 1
- MWLXTCVMCIMSMK-UHFFFAOYSA-N 1-[2-chloro-4-(6,7-dimethoxyquinolin-4-yl)oxyphenyl]-3-(5-chloro-1,3-thiazol-2-yl)urea Chemical compound C=12C=C(OC)C(OC)=CC2=NC=CC=1OC(C=C1Cl)=CC=C1NC(=O)NC1=NC=C(Cl)S1 MWLXTCVMCIMSMK-UHFFFAOYSA-N 0.000 claims 1
- DWVVWQLGUFVMCB-UHFFFAOYSA-N 1-[3-chloro-4-(6,7-dimethoxyquinazolin-4-yl)oxyphenyl]-3-(5-methyl-1,2-oxazol-3-yl)urea Chemical compound C=12C=C(OC)C(OC)=CC2=NC=NC=1OC(C(=C1)Cl)=CC=C1NC(=O)NC=1C=C(C)ON=1 DWVVWQLGUFVMCB-UHFFFAOYSA-N 0.000 claims 1
- WIRDKETWZWQJLR-UHFFFAOYSA-N 1-[3-chloro-4-(6,7-dimethoxyquinolin-4-yl)oxyphenyl]-3-(5-cyclopropyl-1,3,4-thiadiazol-2-yl)urea Chemical compound C=12C=C(OC)C(OC)=CC2=NC=CC=1OC(C(=C1)Cl)=CC=C1NC(=O)NC(S1)=NN=C1C1CC1 WIRDKETWZWQJLR-UHFFFAOYSA-N 0.000 claims 1
- BKBXTGQXCAWPFH-UHFFFAOYSA-N 1-[4-(6,7-dimethoxyquinazolin-4-yl)oxyphenyl]-3-(5-methyl-1,3-thiazol-2-yl)urea Chemical compound C=12C=C(OC)C(OC)=CC2=NC=NC=1OC(C=C1)=CC=C1NC(=O)NC1=NC=C(C)S1 BKBXTGQXCAWPFH-UHFFFAOYSA-N 0.000 claims 1
- DGHAZJIGKPTPJP-UHFFFAOYSA-N 1-[4-(6,7-dimethoxyquinolin-4-yl)oxy-2-fluorophenyl]-3-(1,3-thiazol-2-yl)urea;hydrochloride Chemical compound Cl.C=12C=C(OC)C(OC)=CC2=NC=CC=1OC(C=C1F)=CC=C1NC(=O)NC1=NC=CS1 DGHAZJIGKPTPJP-UHFFFAOYSA-N 0.000 claims 1
- DXQAQQWRNJEJBW-UHFFFAOYSA-N 1-[4-(6,7-dimethoxyquinolin-4-yl)oxy-2-fluorophenyl]-3-(4-methyl-1,3-thiazol-2-yl)urea;hydrochloride Chemical compound Cl.C=12C=C(OC)C(OC)=CC2=NC=CC=1OC(C=C1F)=CC=C1NC(=O)NC1=NC(C)=CS1 DXQAQQWRNJEJBW-UHFFFAOYSA-N 0.000 claims 1
- FNTLOELYFGZSCH-UHFFFAOYSA-N 1-[4-(6,7-dimethoxyquinolin-4-yl)oxy-2-fluorophenyl]-3-[5-(trifluoromethyl)-1,3,4-thiadiazol-2-yl]urea Chemical compound C=12C=C(OC)C(OC)=CC2=NC=CC=1OC(C=C1F)=CC=C1NC(=O)NC1=NN=C(C(F)(F)F)S1 FNTLOELYFGZSCH-UHFFFAOYSA-N 0.000 claims 1
- 125000003545 alkoxy group Chemical group 0.000 abstract description 7
- 230000000259 anti-tumor effect Effects 0.000 abstract description 7
- 229910052760 oxygen Inorganic materials 0.000 abstract description 3
- 230000003389 potentiating effect Effects 0.000 abstract description 3
- 229910052717 sulfur Inorganic materials 0.000 abstract description 3
- 229910052736 halogen Inorganic materials 0.000 abstract 1
- 150000002367 halogens Chemical class 0.000 abstract 1
- 239000000243 solution Substances 0.000 description 323
- 239000000203 mixture Substances 0.000 description 222
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 189
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 150
- 239000012044 organic layer Substances 0.000 description 114
- 238000006243 chemical reaction Methods 0.000 description 79
- UCPYLLCMEDAXFR-UHFFFAOYSA-N triphosgene Chemical compound ClC(Cl)(Cl)OC(=O)OC(Cl)(Cl)Cl UCPYLLCMEDAXFR-UHFFFAOYSA-N 0.000 description 76
- 238000004949 mass spectrometry Methods 0.000 description 75
- 238000005160 1H NMR spectroscopy Methods 0.000 description 73
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 73
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 71
- 238000000605 extraction Methods 0.000 description 66
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 51
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 51
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 51
- 238000011161 development Methods 0.000 description 50
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 45
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 43
- 238000004128 high performance liquid chromatography Methods 0.000 description 40
- 239000012153 distilled water Substances 0.000 description 36
- 229910052938 sodium sulfate Inorganic materials 0.000 description 36
- 235000011152 sodium sulphate Nutrition 0.000 description 36
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 35
- 238000004587 chromatography analysis Methods 0.000 description 27
- 239000013078 crystal Substances 0.000 description 26
- 238000012360 testing method Methods 0.000 description 21
- 101150041968 CDC13 gene Proteins 0.000 description 19
- ZFGMJQSRPRXGMR-UHFFFAOYSA-N 4-(6,7-dimethoxyquinolin-4-yl)oxy-2-fluoroaniline Chemical compound C=12C=C(OC)C(OC)=CC2=NC=CC=1OC1=CC=C(N)C(F)=C1 ZFGMJQSRPRXGMR-UHFFFAOYSA-N 0.000 description 18
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 18
- 238000001914 filtration Methods 0.000 description 17
- 239000007787 solid Substances 0.000 description 17
- 210000004027 cell Anatomy 0.000 description 16
- 150000003246 quinazolines Chemical class 0.000 description 16
- 229920006395 saturated elastomer Polymers 0.000 description 16
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 13
- 108010053099 Vascular Endothelial Growth Factor Receptor-2 Proteins 0.000 description 11
- MSAYDMJFSCQXQL-UHFFFAOYSA-N 2-chloro-4-(6,7-dimethoxyquinolin-4-yl)oxyaniline Chemical compound C=12C=C(OC)C(OC)=CC2=NC=CC=1OC1=CC=C(N)C(Cl)=C1 MSAYDMJFSCQXQL-UHFFFAOYSA-N 0.000 description 10
- 125000000623 heterocyclic group Chemical group 0.000 description 10
- 230000005764 inhibitory process Effects 0.000 description 10
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 10
- 238000002425 crystallisation Methods 0.000 description 9
- 230000008025 crystallization Effects 0.000 description 9
- 229940079593 drug Drugs 0.000 description 9
- 239000005457 ice water Substances 0.000 description 9
- 239000000741 silica gel Substances 0.000 description 9
- 229910002027 silica gel Inorganic materials 0.000 description 9
- 239000002904 solvent Substances 0.000 description 9
- 230000004614 tumor growth Effects 0.000 description 9
- QXTRPGAMVIONMK-UHFFFAOYSA-N 2-amino-5-ethyl-1,3,4-thiadiazole Chemical compound CCC1=NN=C(N)S1 QXTRPGAMVIONMK-UHFFFAOYSA-N 0.000 description 8
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 8
- 108010073929 Vascular Endothelial Growth Factor A Proteins 0.000 description 8
- 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 description 8
- 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 description 8
- XMXLBDNVSIHRRA-UHFFFAOYSA-N 2-amino-4,5-dimethyl-thiazole Natural products CC=1N=C(N)SC=1C XMXLBDNVSIHRRA-UHFFFAOYSA-N 0.000 description 7
- JWNJXRODWCORFX-UHFFFAOYSA-N 2-chloro-4-(6,7-dimethoxyquinazolin-4-yl)oxyaniline Chemical compound C=12C=C(OC)C(OC)=CC2=NC=NC=1OC1=CC=C(N)C(Cl)=C1 JWNJXRODWCORFX-UHFFFAOYSA-N 0.000 description 7
- FECRYRZVCNTJHP-UHFFFAOYSA-N 3-chloro-4-(6,7-dimethoxyquinazolin-4-yl)oxyaniline Chemical compound C=12C=C(OC)C(OC)=CC2=NC=NC=1OC1=CC=C(N)C=C1Cl FECRYRZVCNTJHP-UHFFFAOYSA-N 0.000 description 7
- DCFZOECVVBSZLL-UHFFFAOYSA-N 3-chloro-4-(6,7-dimethoxyquinolin-4-yl)oxyaniline Chemical compound C=12C=C(OC)C(OC)=CC2=NC=CC=1OC1=CC=C(N)C=C1Cl DCFZOECVVBSZLL-UHFFFAOYSA-N 0.000 description 7
- FNXYWHTZDAVRTB-UHFFFAOYSA-N 3-methyl-1,2-oxazol-5-amine Chemical compound CC=1C=C(N)ON=1 FNXYWHTZDAVRTB-UHFFFAOYSA-N 0.000 description 7
- XYTUTNQRQLAZLK-UHFFFAOYSA-N 4,5-dimethyl-1,3-thiazol-2-amine;hydrochloride Chemical compound Cl.CC=1N=C(N)SC=1C XYTUTNQRQLAZLK-UHFFFAOYSA-N 0.000 description 7
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 7
- 230000026731 phosphorylation Effects 0.000 description 7
- 238000006366 phosphorylation reaction Methods 0.000 description 7
- ZLVVYBNEDMWIRX-UHFFFAOYSA-N 4-(6,7-dimethoxyquinazolin-4-yl)oxyaniline Chemical compound C=12C=C(OC)C(OC)=CC2=NC=NC=1OC1=CC=C(N)C=C1 ZLVVYBNEDMWIRX-UHFFFAOYSA-N 0.000 description 6
- LTEUXHSAYOSFGQ-UHFFFAOYSA-N 5-(trifluoromethyl)-1,3,4-thiadiazol-2-amine Chemical compound NC1=NN=C(C(F)(F)F)S1 LTEUXHSAYOSFGQ-UHFFFAOYSA-N 0.000 description 6
- FKPXGNGUVSHWQQ-UHFFFAOYSA-N 5-methyl-1,2-oxazol-3-amine Chemical compound CC1=CC(N)=NO1 FKPXGNGUVSHWQQ-UHFFFAOYSA-N 0.000 description 6
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
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- 125000002837 carbocyclic group Chemical group 0.000 description 6
- 125000005842 heteroatom Chemical group 0.000 description 6
- 229910052757 nitrogen Inorganic materials 0.000 description 6
- 230000000144 pharmacologic effect Effects 0.000 description 6
- PCSIZCXZPLZZCD-UHFFFAOYSA-N 2-quinolin-4-yloxyaniline Chemical class NC1=CC=CC=C1OC1=CC=NC2=CC=CC=C12 PCSIZCXZPLZZCD-UHFFFAOYSA-N 0.000 description 5
- ZKPSHRUKJGWIHO-UHFFFAOYSA-N 4-(6,7-dimethoxyquinolin-4-yl)oxy-2,3-dimethylaniline Chemical compound C=12C=C(OC)C(OC)=CC2=NC=CC=1OC1=CC=C(N)C(C)=C1C ZKPSHRUKJGWIHO-UHFFFAOYSA-N 0.000 description 5
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- 239000002585 base Substances 0.000 description 5
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- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 5
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- 238000005406 washing Methods 0.000 description 5
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- AVLUMBXGKFNNAS-UHFFFAOYSA-N 5-cyclopropyl-1,3,4-thiadiazol-2-amine Chemical compound S1C(N)=NN=C1C1CC1 AVLUMBXGKFNNAS-UHFFFAOYSA-N 0.000 description 3
- GUABFMPMKJGSBQ-UHFFFAOYSA-N 5-methyl-1,3-thiazol-2-amine Chemical compound CC1=CN=C(N)S1 GUABFMPMKJGSBQ-UHFFFAOYSA-N 0.000 description 3
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- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 3
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- 102000055590 human KDR Human genes 0.000 description 3
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- 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 1
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- 239000000975 dye Substances 0.000 description 1
- CCIVGXIOQKPBKL-UHFFFAOYSA-N ethanesulfonic acid Chemical class CCS(O)(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-N 0.000 description 1
- 235000019325 ethyl cellulose Nutrition 0.000 description 1
- 229920001249 ethyl cellulose Polymers 0.000 description 1
- 125000004705 ethylthio group Chemical group C(C)S* 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
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- 239000008187 granular material Substances 0.000 description 1
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- 125000006038 hexenyl group Chemical group 0.000 description 1
- 125000005980 hexynyl group Chemical group 0.000 description 1
- 150000003840 hydrochlorides Chemical class 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical class I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- 239000008172 hydrogenated vegetable oil Substances 0.000 description 1
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 1
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 1
- 125000002883 imidazolyl group Chemical group 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 125000001786 isothiazolyl group Chemical group 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical class CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
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- 235000019359 magnesium stearate Nutrition 0.000 description 1
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- 150000004701 malic acid derivatives Chemical class 0.000 description 1
- UKVIEHSSVKSQBA-UHFFFAOYSA-N methane;palladium Chemical compound C.[Pd] UKVIEHSSVKSQBA-UHFFFAOYSA-N 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
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- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
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- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
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- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- NXJCBFBQEVOTOW-UHFFFAOYSA-L palladium(2+);dihydroxide Chemical compound O[Pd]O NXJCBFBQEVOTOW-UHFFFAOYSA-L 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 125000002255 pentenyl group Chemical group C(=CCCC)* 0.000 description 1
- 125000005981 pentynyl group Chemical group 0.000 description 1
- VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical class OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 239000003444 phase transfer catalyst Substances 0.000 description 1
- 150000002994 phenylalanines Chemical class 0.000 description 1
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- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 1
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- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 159000000001 potassium salts Chemical class 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 125000004076 pyridyl group Chemical group 0.000 description 1
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 1
- 125000006413 ring segment Chemical group 0.000 description 1
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- 235000019698 starch Nutrition 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N succinic acid Chemical class OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- HXJUTPCZVOIRIF-UHFFFAOYSA-N sulfolane Chemical compound O=S1(=O)CCCC1 HXJUTPCZVOIRIF-UHFFFAOYSA-N 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
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- JRMUNVKIHCOMHV-UHFFFAOYSA-M tetrabutylammonium bromide Chemical compound [Br-].CCCC[N+](CCCC)(CCCC)CCCC JRMUNVKIHCOMHV-UHFFFAOYSA-M 0.000 description 1
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical class CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
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- ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical class OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/06—Antipsoriatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Diabetes (AREA)
- Heart & Thoracic Surgery (AREA)
- Rheumatology (AREA)
- Cardiology (AREA)
- Immunology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Endocrinology (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Pain & Pain Management (AREA)
- Urology & Nephrology (AREA)
- Ophthalmology & Optometry (AREA)
- Vascular Medicine (AREA)
- Emergency Medicine (AREA)
- Physical Education & Sports Medicine (AREA)
- Dermatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Luminescent Compositions (AREA)
- Adhesives Or Adhesive Processes (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Agricultural Chemicals And Associated Chemicals (AREA)
- Polymerization Catalysts (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2001132775 | 2001-04-27 | ||
| PCT/JP2002/004279 WO2002088110A1 (en) | 2001-04-27 | 2002-04-26 | Quinoline derivative having azolyl group and quinazoline derivative |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| NO20034595D0 NO20034595D0 (no) | 2003-10-14 |
| NO20034595L NO20034595L (no) | 2003-12-19 |
| NO326325B1 true NO326325B1 (no) | 2008-11-10 |
Family
ID=18980738
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO20034595A NO326325B1 (no) | 2001-04-27 | 2003-10-14 | Kinolin- og kinazolinderivater med azolylgruppe |
| NO2018005C NO2018005I1 (no) | 2001-04-27 | 2018-02-05 | tivozanib eller et salt eller solvat derav |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO2018005C NO2018005I1 (no) | 2001-04-27 | 2018-02-05 | tivozanib eller et salt eller solvat derav |
Country Status (24)
| Country | Link |
|---|---|
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| EP (2) | EP1652847B1 (enExample) |
| JP (1) | JP2010077131A (enExample) |
| KR (1) | KR100879669B1 (enExample) |
| CN (1) | CN1273466C (enExample) |
| AT (1) | ATE396988T1 (enExample) |
| AU (1) | AU2002255284B2 (enExample) |
| BE (1) | BE2018C008I2 (enExample) |
| BR (1) | BRPI0209216B8 (enExample) |
| CA (1) | CA2445333C (enExample) |
| DE (2) | DE60208364T2 (enExample) |
| DK (1) | DK1382604T3 (enExample) |
| ES (1) | ES2256466T3 (enExample) |
| FR (1) | FR18C1006I2 (enExample) |
| IL (1) | IL158459A0 (enExample) |
| MX (1) | MXPA03009662A (enExample) |
| NL (1) | NL300927I9 (enExample) |
| NO (2) | NO326325B1 (enExample) |
| NZ (1) | NZ529046A (enExample) |
| PL (1) | PL209822B1 (enExample) |
| RU (1) | RU2283841C2 (enExample) |
| TW (1) | TWI324154B (enExample) |
| WO (1) | WO2002088110A1 (enExample) |
| ZA (1) | ZA200307861B (enExample) |
Families Citing this family (88)
| Publication number | Priority date | Publication date | Assignee | Title |
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| EP1384712B1 (en) * | 1999-01-22 | 2007-03-07 | Kirin Beer Kabushiki Kaisha | Derivatives of N-((quinolinyl)oxy)-phenyl)-urea and N-((quinazolinyl)oxy)-phenyl)-urea with antitumor activity |
| WO2001047890A1 (en) * | 1999-12-24 | 2001-07-05 | Kirin Beer Kabushiki Kaisha | Quinoline and quinazoline derivatives and drugs containing the same |
| US6489125B1 (en) * | 2000-05-10 | 2002-12-03 | The Trustees Of Columbia University In The City Of New York | Methods for identifying chemical compounds that inhibit dissociation of FKBP12.6 binding protein from type 2 ryanodine receptor |
| US7718644B2 (en) * | 2004-01-22 | 2010-05-18 | The Trustees Of Columbia University In The City Of New York | Anti-arrhythmic and heart failure drugs that target the leak in the ryanodine receptor (RyR2) and uses thereof |
| US20040229781A1 (en) * | 2000-05-10 | 2004-11-18 | Marks Andrew Robert | Compounds and methods for treating and preventing exercise-induced cardiac arrhythmias |
| US8022058B2 (en) | 2000-05-10 | 2011-09-20 | The Trustees Of Columbia University In The City Of New York | Agents for preventing and treating disorders involving modulation of the RyR receptors |
| US7393652B2 (en) | 2000-05-10 | 2008-07-01 | The Trustees Of Columbia University In The City Of New York | Methods for identifying a chemical compound that directly enhances binding of FKBP12.6 to PKA-phosphorylated type 2 ryanodine receptor (RyR2) |
| US20060293266A1 (en) * | 2000-05-10 | 2006-12-28 | The Trustees Of Columbia | Phosphodiesterase 4D in the ryanodine receptor complex protects against heart failure |
| US20040048780A1 (en) * | 2000-05-10 | 2004-03-11 | The Trustees Of Columbia University In The City Of New York | Method for treating and preventing cardiac arrhythmia |
| US7879840B2 (en) * | 2005-08-25 | 2011-02-01 | The Trustees Of Columbia University In The City Of New York | Agents for preventing and treating disorders involving modulation of the RyR receptors |
| JP3712393B2 (ja) * | 2000-10-20 | 2005-11-02 | エーザイ株式会社 | 含窒素芳香環誘導体 |
| EP1652847B1 (en) * | 2001-04-27 | 2008-05-28 | Kirin Pharma Kabushiki Kaisha | Quinoline and quinazoline derivatives for the treatment of tumors |
| EP2258366B1 (en) * | 2001-06-22 | 2013-04-03 | Kirin Pharma Kabushiki Kaisha | Quinoline derivatives capable of inhibiting autophosphorylation of hepatocyte growth factor receptors, and pharmaceutical composition comprising the same |
| EP1447405A4 (en) * | 2001-10-17 | 2005-01-12 | Kirin Brewery | CHINOLIN OR CHINAZOLINE DERIVATIVES THAT PREVENT THE AUTOPHOSPHORYLATION OF RECEPTORS FOR THE FIBROBLAST GROWTH FACTOR |
| JPWO2003093238A1 (ja) * | 2002-05-01 | 2005-09-08 | 麒麟麦酒株式会社 | マクロファージコロニー刺激因子受容体自己リン酸化を阻害するキノリン誘導体およびキナゾリン誘導体 |
| EP2280003B1 (en) | 2002-07-15 | 2014-04-02 | Symphony Evolution, Inc. | Process for preparing receptor-type kinase modulators |
| PT1559715E (pt) * | 2002-10-21 | 2007-10-24 | Kirin Pharma Kk | Formas cristalinas de sais de n-[2-cloro-4-[6, 7-dimetoxi-4-quinolil)oxi]finil]-n'-(5-metil-3-isoxazolil) ureia |
| WO2004039782A1 (ja) * | 2002-10-29 | 2004-05-13 | Kirin Beer Kabushiki Kaisha | Ｆｌｔ３自己リン酸化を阻害するキノリン誘導体およびキナゾリン誘導体並びにそれらを含有する医薬組成物 |
| US7544678B2 (en) * | 2002-11-05 | 2009-06-09 | The Trustees Of Columbia University In The City Of New York | Anti-arrythmic and heart failure drugs that target the leak in the ryanodine receptor (RyR2) |
| AU2003292838A1 (en) * | 2002-12-27 | 2004-07-29 | Kirin Beer Kabushiki Kaisha | Therapeutic agent for wet age-related macular degeneration |
| EP1603450A4 (en) | 2003-03-07 | 2009-07-29 | Univ Columbia | PROCEDURE BASED ON TYPE 1 RYANODIN RECEPTOR |
| WO2004080462A1 (ja) * | 2003-03-10 | 2004-09-23 | Eisai Co., Ltd. | c-Kitキナーゼ阻害剤 |
| WO2005030140A2 (en) | 2003-09-26 | 2005-04-07 | Exelixis, Inc. | C-met modulators and methods of use |
| WO2005044788A1 (ja) * | 2003-11-11 | 2005-05-19 | Eisai Co., Ltd. | ウレア誘導体およびその製造方法 |
| US20050192314A1 (en) * | 2003-11-13 | 2005-09-01 | Ambit Biosciences Corporation | Urea derivatives as C-kit modulators |
| US8710045B2 (en) * | 2004-01-22 | 2014-04-29 | The Trustees Of Columbia University In The City Of New York | Agents for preventing and treating disorders involving modulation of the ryanodine receptors |
| AU2005207946A1 (en) * | 2004-01-23 | 2005-08-11 | Amgen Inc. | Quinoline quinazoline pyridine and pyrimidine counds and their use in the treatment of inflammation angiogenesis and cancer |
| TW200530236A (en) | 2004-02-23 | 2005-09-16 | Chugai Pharmaceutical Co Ltd | Heteroaryl phenylurea |
| EP1797881B1 (en) * | 2004-09-17 | 2009-04-15 | Eisai R&D Management Co., Ltd. | Medicinal composition with improved stability and reduced gelation properties |
| JP2008537748A (ja) * | 2005-04-06 | 2008-09-25 | エクセリクシス、インコーポレイテッド | ｃ−Ｍｅｔモジュレーター及び使用方法 |
| TW200740820A (en) * | 2005-07-05 | 2007-11-01 | Takeda Pharmaceuticals Co | Fused heterocyclic derivatives and use thereof |
| WO2007015569A1 (ja) * | 2005-08-01 | 2007-02-08 | Eisai R & D Management Co., Ltd. | 血管新生阻害物質の効果を予測する方法 |
| US9006240B2 (en) | 2005-08-02 | 2015-04-14 | Eisai R&D Management Co., Ltd. | Method for assay on the effect of vascularization inhibitor |
| US7704990B2 (en) * | 2005-08-25 | 2010-04-27 | The Trustees Of Columbia University In The City Of New York | Agents for preventing and treating disorders involving modulation of the RyR receptors |
| CN101277720A (zh) * | 2005-09-01 | 2008-10-01 | 卫材R&D管理有限公司 | 崩解性被改善的药物组合物的制备方法 |
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| JP2728878B2 (ja) | 1987-12-15 | 1998-03-18 | 大倉工業株式会社 | 中空押出成形板 |
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| DE1041982T1 (de) * | 1997-12-22 | 2001-06-07 | Bayer Corp., Pittsburgh | HEMMUNG DER p38 KINASE AKTIVITÄT DURCH SUBSTITUIERTEN HETEROCYCLISCHEN HARNSTOFFEN |
| PL205321B1 (pl) * | 1997-12-22 | 2010-04-30 | Bayer Corp | Zastosowanie podstawionych heterocyklicznych moczników do wytwarzania leku do hamowania kinazy raf, podstawione heterocykliczne moczniki oraz kompozycja farmaceutyczna je zawierająca |
| EP1384712B1 (en) * | 1999-01-22 | 2007-03-07 | Kirin Beer Kabushiki Kaisha | Derivatives of N-((quinolinyl)oxy)-phenyl)-urea and N-((quinazolinyl)oxy)-phenyl)-urea with antitumor activity |
| WO2001047890A1 (en) * | 1999-12-24 | 2001-07-05 | Kirin Beer Kabushiki Kaisha | Quinoline and quinazoline derivatives and drugs containing the same |
| JP2002030083A (ja) | 2000-07-18 | 2002-01-29 | Kirin Brewery Co Ltd | Ｎ−（２−クロロ−４−｛［６−メトキシ−７−（３−ピリジルメトキシ）−４−キノリル］オキシ｝フェニル）−ｎ’−プロピルウレアの二塩酸塩 |
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