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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- 235000019325 ethyl cellulose Nutrition 0.000 description 1
- 229920001249 ethyl cellulose Polymers 0.000 description 1
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- 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
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- 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
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- 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
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- 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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- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 159000000001 potassium salts Chemical class 0.000 description 1
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- 239000007858 starting material Substances 0.000 description 1
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- 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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Classifications
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- 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
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- 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
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- 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]
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- 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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- 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
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- General Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Diabetes (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Rheumatology (AREA)
- Vascular Medicine (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Endocrinology (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Pain & Pain Management (AREA)
- Urology & Nephrology (AREA)
- Ophthalmology & Optometry (AREA)
- Immunology (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)
- Polymerization Catalysts (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Agricultural Chemicals And Associated Chemicals (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 |
|---|---|
| US (2) | US6821987B2 (online.php) |
| EP (2) | EP1382604B1 (online.php) |
| JP (1) | JP2010077131A (online.php) |
| KR (1) | KR100879669B1 (online.php) |
| CN (1) | CN1273466C (online.php) |
| AT (1) | ATE396988T1 (online.php) |
| AU (1) | AU2002255284B2 (online.php) |
| BE (1) | BE2018C008I2 (online.php) |
| BR (1) | BRPI0209216B8 (online.php) |
| CA (1) | CA2445333C (online.php) |
| DE (2) | DE60208364T2 (online.php) |
| DK (1) | DK1382604T3 (online.php) |
| ES (1) | ES2256466T3 (online.php) |
| FR (1) | FR18C1006I2 (online.php) |
| IL (1) | IL158459A0 (online.php) |
| MX (1) | MXPA03009662A (online.php) |
| NL (1) | NL300927I9 (online.php) |
| NO (2) | NO326325B1 (online.php) |
| NZ (1) | NZ529046A (online.php) |
| PL (1) | PL209822B1 (online.php) |
| RU (1) | RU2283841C2 (online.php) |
| TW (1) | TWI324154B (online.php) |
| WO (1) | WO2002088110A1 (online.php) |
| ZA (1) | ZA200307861B (online.php) |
Families Citing this family (89)
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| CA2361057C (en) * | 1999-01-22 | 2010-04-06 | Kazuo Kubo | Quinoline derivatives and quinazoline derivatives |
| US7135466B2 (en) * | 1999-12-24 | 2006-11-14 | Kirin Beer Kabushiki Kaisha | Quinoline and quinazoline derivatives and drugs containing the same |
| 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 |
| 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 |
| EP1415987B1 (en) * | 2000-10-20 | 2007-02-28 | Eisai R&D Management Co., Ltd. | Nitrogenous aromatic ring compounds as anti cancer agents |
| DE60208364T2 (de) | 2001-04-27 | 2006-09-28 | Kirin Beer K.K. | Chinolinderivate mit einer azolylgruppe und chinazolinderivate |
| CA2454538A1 (en) * | 2001-06-22 | 2003-01-03 | Kirin Beer Kabushiki Kaisha | Quinoline derivatives and quinazoline derivatives capable of inhibiting autophosphorylation of hepatocyte growth factor receptors, and pharmaceutical composition comprising the same |
| WO2003033472A1 (en) * | 2001-10-17 | 2003-04-24 | Kirin Beer Kabushiki Kaisha | Quinoline or quinazoline derivatives inhibiting auto- phosphorylation of fibroblast growth factor receptors |
| US7598258B2 (en) * | 2002-05-01 | 2009-10-06 | Kirin Beer Kabushiki Kaisha | Quinoline derivatives and quinazoline derivatives inhibiting autophosphorylation of macrophage colony stimulating factor receptor |
| ES2400339T3 (es) | 2002-07-15 | 2013-04-09 | Symphony Evolution, Inc. | Compuestos, composiciones farmacéuticas de los mismos y su uso en el tratamiento del cáncer |
| JP3763414B2 (ja) * | 2002-10-21 | 2006-04-05 | 麒麟麦酒株式会社 | Ｎ−｛２−クロロ−４−［（６，７−ジメトキシ−４−キノリル）オキシ］フェニル｝−ｎ’−（５−メチル−３−イソキサゾリル）ウレアの塩の結晶形 |
| EP1566379A4 (en) * | 2002-10-29 | 2005-11-09 | Kirin Brewery | CHINOLINE DERIVATIVES AND CHINAZOLINE DERIVATIVES AS INHIBITORS OF FLT3 AUTOPHOSPHORYLATION AND THE MEDICAL COMPOSITIONS CONTAINING THEREOF |
| 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) |
| WO2004060373A1 (ja) * | 2002-12-27 | 2004-07-22 | Santen Pharmaceutical Co., Ltd. | 滲出型加齢黄斑変性治療剤 |
| AU2004220548A1 (en) | 2003-03-07 | 2004-09-23 | The Trustees Of Columbia University, In The City Of New York | Type 1 ryanodine receptor-based methods |
| EP1604665B1 (en) * | 2003-03-10 | 2011-05-11 | Eisai R&D Management Co., Ltd. | C-kit kinase inhibitor |
| CA2744997A1 (en) | 2003-09-26 | 2005-04-07 | Exelixis, Inc. | C-met modulators and method 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 |
| US20050267182A1 (en) * | 2003-11-13 | 2005-12-01 | Ambit Biosciences Corporation | Urea derivatives as FLT-3 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 |
| CA2553433A1 (en) * | 2004-01-23 | 2005-08-11 | Amgen Inc. | Quinoline quinazoline pyridine and pyrimidine compounds 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 |
| ATE428421T1 (de) * | 2004-09-17 | 2009-05-15 | Eisai R&D Man Co Ltd | Medizinische zusammensetzung mit verbesserter stabilität und reduzierten gelierungseigenschaften |
| 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 |
| EP1925676A4 (en) | 2005-08-02 | 2010-11-10 | Eisai R&D Man Co Ltd | TEST METHOD FOR THE EFFECT OF A 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 |
| EP1938842A4 (en) * | 2005-09-01 | 2013-01-09 | Eisai R&D Man Co Ltd | METHOD FOR PRODUCING A PHARMACEUTICAL COMPOSITION COMPRISING IMPROVED CRASHING CHARACTERISTICS |
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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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| EP1415987B1 (en) * | 2000-10-20 | 2007-02-28 | Eisai R&D Management Co., Ltd. | Nitrogenous aromatic ring compounds as anti cancer agents |
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