NO310658B1 - Kinozolinderivater, farmasöytisk preparat inneholdende slike derivater, anvendelse derav, og fremgangsmåte for deresfremstilling - Google Patents
Kinozolinderivater, farmasöytisk preparat inneholdende slike derivater, anvendelse derav, og fremgangsmåte for deresfremstilling Download PDFInfo
- Publication number
- NO310658B1 NO310658B1 NO19961601A NO961601A NO310658B1 NO 310658 B1 NO310658 B1 NO 310658B1 NO 19961601 A NO19961601 A NO 19961601A NO 961601 A NO961601 A NO 961601A NO 310658 B1 NO310658 B1 NO 310658B1
- Authority
- NO
- Norway
- Prior art keywords
- compound
- lower alkyl
- formula
- quinazolinyl
- piperidinyl
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 82
- 238000002360 preparation method Methods 0.000 title claims description 19
- 239000000825 pharmaceutical preparation Substances 0.000 title claims description 6
- 150000001875 compounds Chemical class 0.000 claims abstract description 201
- 150000003839 salts Chemical class 0.000 claims abstract description 35
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 34
- -1 methylenedioxy Chemical group 0.000 claims abstract description 26
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 20
- 239000001257 hydrogen Substances 0.000 claims abstract description 20
- OIRDTQYFTABQOQ-KQYNXXCUSA-N adenosine Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O OIRDTQYFTABQOQ-KQYNXXCUSA-N 0.000 claims abstract description 14
- 239000002126 C01EB10 - Adenosine Substances 0.000 claims abstract description 10
- 229960005305 adenosine Drugs 0.000 claims abstract description 10
- 230000002401 inhibitory effect Effects 0.000 claims abstract description 9
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 8
- 125000003710 aryl alkyl group Chemical group 0.000 claims abstract description 8
- 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 7
- 206010061218 Inflammation Diseases 0.000 claims abstract description 5
- 230000004054 inflammatory process Effects 0.000 claims abstract description 5
- 210000004165 myocardium Anatomy 0.000 claims abstract description 5
- 125000002102 aryl alkyloxo group Chemical group 0.000 claims abstract description 4
- 125000001589 carboacyl group Chemical group 0.000 claims abstract description 4
- 230000002265 prevention Effects 0.000 claims abstract description 4
- 125000002294 quinazolinyl group Chemical class N1=C(N=CC2=CC=CC=C12)* 0.000 claims abstract 3
- 239000002904 solvent Substances 0.000 claims description 35
- 238000006243 chemical reaction Methods 0.000 claims description 16
- 150000002431 hydrogen Chemical class 0.000 claims description 9
- 229910052801 chlorine Inorganic materials 0.000 claims description 8
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 8
- 125000001424 substituent group Chemical group 0.000 claims description 8
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 7
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 7
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 7
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 7
- 229910052794 bromium Inorganic materials 0.000 claims description 7
- 239000000460 chlorine Substances 0.000 claims description 7
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 6
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 6
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 6
- 238000010531 catalytic reduction reaction Methods 0.000 claims description 5
- 150000001412 amines Chemical class 0.000 claims description 4
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 4
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 4
- 239000007868 Raney catalyst Substances 0.000 claims description 3
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 claims description 3
- 229910000564 Raney nickel Inorganic materials 0.000 claims description 3
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims description 3
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 3
- 239000003054 catalyst Substances 0.000 claims description 3
- 229910052736 halogen Inorganic materials 0.000 claims description 3
- 150000002367 halogens Chemical class 0.000 claims description 3
- 239000011133 lead Substances 0.000 claims description 3
- MUMZUERVLWJKNR-UHFFFAOYSA-N oxoplatinum Chemical compound [Pt]=O MUMZUERVLWJKNR-UHFFFAOYSA-N 0.000 claims description 3
- 229910003446 platinum oxide Inorganic materials 0.000 claims description 3
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 3
- 206010030113 Oedema Diseases 0.000 claims description 2
- 239000004480 active ingredient Substances 0.000 claims description 2
- 238000009833 condensation Methods 0.000 claims description 2
- 230000005494 condensation Effects 0.000 claims description 2
- 239000003814 drug Substances 0.000 claims description 2
- 238000007363 ring formation reaction Methods 0.000 claims description 2
- 230000001225 therapeutic effect Effects 0.000 claims description 2
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims 1
- 206010030124 Oedema peripheral Diseases 0.000 abstract description 6
- 125000004435 hydrogen atom Chemical class [H]* 0.000 abstract description 6
- 125000000753 cycloalkyl group Chemical group 0.000 abstract description 4
- 125000003342 alkenyl group Chemical group 0.000 abstract 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 abstract 1
- 238000005160 1H NMR spectroscopy Methods 0.000 description 75
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 70
- 238000002844 melting Methods 0.000 description 69
- 230000008018 melting Effects 0.000 description 69
- 239000013078 crystal Substances 0.000 description 68
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 46
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 39
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 39
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 33
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 27
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 24
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 18
- NZSDBOVMMXQQPC-UHFFFAOYSA-N 3-[1-(2-chloro-6,7-diethoxyquinazolin-4-yl)piperidin-4-yl]-6-methyl-1h-quinazoline-2,4-dione Chemical compound O=C1NC2=CC=C(C)C=C2C(=O)N1C(CC1)CCN1C1=C(C=C(C(OCC)=C2)OCC)C2=NC(Cl)=N1 NZSDBOVMMXQQPC-UHFFFAOYSA-N 0.000 description 17
- GBMDVOWEEQVZKZ-UHFFFAOYSA-N methanol;hydrate Chemical compound O.OC GBMDVOWEEQVZKZ-UHFFFAOYSA-N 0.000 description 17
- 239000012458 free base Substances 0.000 description 15
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 14
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 14
- 239000000203 mixture Substances 0.000 description 14
- SRCZQMGIVIYBBJ-UHFFFAOYSA-N ethoxyethane;ethyl acetate Chemical compound CCOCC.CCOC(C)=O SRCZQMGIVIYBBJ-UHFFFAOYSA-N 0.000 description 11
- 239000000243 solution Substances 0.000 description 11
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 11
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 10
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 9
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 9
- 244000309464 bull Species 0.000 description 9
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 8
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 8
- DGHKCBSVAZXEPP-UHFFFAOYSA-N 2,4-dichloro-6,7-dimethoxyquinazoline Chemical compound ClC1=NC(Cl)=C2C=C(OC)C(OC)=CC2=N1 DGHKCBSVAZXEPP-UHFFFAOYSA-N 0.000 description 7
- 239000002585 base Substances 0.000 description 7
- 238000001914 filtration Methods 0.000 description 7
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 7
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 6
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 6
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
- 238000009835 boiling Methods 0.000 description 6
- WGYKZJWCGVVSQN-UHFFFAOYSA-N propylamine Chemical compound CCCN WGYKZJWCGVVSQN-UHFFFAOYSA-N 0.000 description 6
- 238000010992 reflux Methods 0.000 description 6
- 239000000725 suspension Substances 0.000 description 6
- OPVFWRJOQBWSLF-UHFFFAOYSA-N 1-[4-[4-(1,6-dimethyl-2,4-dioxoquinazolin-3-yl)piperidin-1-yl]-6,7-dimethoxyquinazolin-2-yl]piperidine-4-carboxylic acid Chemical compound N=1C(N2CCC(CC2)N2C(C3=CC(C)=CC=C3N(C)C2=O)=O)=C2C=C(OC)C(OC)=CC2=NC=1N1CCC(C(O)=O)CC1 OPVFWRJOQBWSLF-UHFFFAOYSA-N 0.000 description 5
- HBDJQOASDJWIBR-UHFFFAOYSA-N 2-amino-n-[2-[1-(6,7-dimethoxy-2-morpholin-4-ylquinazolin-4-yl)piperidin-4-yl]ethyl]-5-methylbenzamide Chemical compound C=12C=C(OC)C(OC)=CC2=NC(N2CCOCC2)=NC=1N(CC1)CCC1CCNC(=O)C1=CC(C)=CC=C1N HBDJQOASDJWIBR-UHFFFAOYSA-N 0.000 description 5
- APZRLSWQGNPICW-UHFFFAOYSA-N 2-amino-n-[2-[1-[2-[bis(2-hydroxyethyl)amino]-6,7-dimethoxyquinazolin-4-yl]piperidin-4-yl]ethyl]-5-methylbenzamide Chemical compound C=12C=C(OC)C(OC)=CC2=NC(N(CCO)CCO)=NC=1N(CC1)CCC1CCNC(=O)C1=CC(C)=CC=C1N APZRLSWQGNPICW-UHFFFAOYSA-N 0.000 description 5
- ZUSZWBVAVBXSQH-UHFFFAOYSA-N 3-[1-(2-chloro-6,7-diethoxyquinazolin-4-yl)piperidin-4-yl]-1,5-dimethylquinazoline-2,4-dione Chemical compound O=C1N(C)C2=CC=CC(C)=C2C(=O)N1C(CC1)CCN1C1=C(C=C(C(OCC)=C2)OCC)C2=NC(Cl)=N1 ZUSZWBVAVBXSQH-UHFFFAOYSA-N 0.000 description 5
- BSGIDGXPKGBGEY-UHFFFAOYSA-N 3-[1-[2-chloro-6,7-di(propan-2-yloxy)quinazolin-4-yl]piperidin-4-yl]-1,6-dimethylquinazoline-2,4-dione Chemical compound O=C1N(C)C2=CC=C(C)C=C2C(=O)N1C(CC1)CCN1C1=C(C=C(C(OC(C)C)=C2)OC(C)C)C2=NC(Cl)=N1 BSGIDGXPKGBGEY-UHFFFAOYSA-N 0.000 description 5
- RHYSOBBFGJHKEO-UHFFFAOYSA-N 3-[[1-(2-chloro-6,7-dimethoxyquinazolin-4-yl)piperidin-4-yl]methyl]-1,6-dimethylquinazoline-2,4-dione Chemical compound O=C1N(C)C2=CC=C(C)C=C2C(=O)N1CC(CC1)CCN1C1=C(C=C(C(OC)=C2)OC)C2=NC(Cl)=N1 RHYSOBBFGJHKEO-UHFFFAOYSA-N 0.000 description 5
- GUQSUWLETQNSTJ-UHFFFAOYSA-N ethyl 4-(1,6-dimethyl-2,4-dioxoquinazolin-3-yl)piperidine-1-carboxylate Chemical compound C1CN(C(=O)OCC)CCC1N1C(=O)C2=CC(C)=CC=C2N(C)C1=O GUQSUWLETQNSTJ-UHFFFAOYSA-N 0.000 description 5
- 238000000605 extraction Methods 0.000 description 5
- 150000003246 quinazolines Chemical class 0.000 description 5
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 4
- HPTIRWCWHNLNEL-UHFFFAOYSA-N 3-[1-(2-chloro-6,7-diethoxyquinazolin-4-yl)piperidin-4-yl]-1,8-dimethylquinazoline-2,4-dione Chemical compound O=C1N(C)C2=C(C)C=CC=C2C(=O)N1C(CC1)CCN1C1=C(C=C(C(OCC)=C2)OCC)C2=NC(Cl)=N1 HPTIRWCWHNLNEL-UHFFFAOYSA-N 0.000 description 4
- QFNDZGQZDWYUJN-UHFFFAOYSA-N 3-[1-(2-chloro-6,7-diethoxyquinazolin-4-yl)piperidin-4-yl]-1-methylquinazoline-2,4-dione Chemical compound O=C1N(C)C2=CC=CC=C2C(=O)N1C(CC1)CCN1C1=C(C=C(C(OCC)=C2)OCC)C2=NC(Cl)=N1 QFNDZGQZDWYUJN-UHFFFAOYSA-N 0.000 description 4
- RDTFXXQWWLQJJJ-UHFFFAOYSA-N 3-[1-(2-chloro-6,7-diethoxyquinazolin-4-yl)piperidin-4-yl]-6-nitro-1h-quinazoline-2,4-dione Chemical compound O=C1NC2=CC=C([N+]([O-])=O)C=C2C(=O)N1C(CC1)CCN1C1=C(C=C(C(OCC)=C2)OCC)C2=NC(Cl)=N1 RDTFXXQWWLQJJJ-UHFFFAOYSA-N 0.000 description 4
- WVQSJJCACLCNDS-UHFFFAOYSA-N 3-[1-(2-chloro-6-methoxy-7-phenylmethoxyquinazolin-4-yl)piperidin-4-yl]-1,6-dimethylquinazoline-2,4-dione Chemical compound COC1=CC2=C(N3CCC(CC3)N3C(C4=CC(C)=CC=C4N(C)C3=O)=O)N=C(Cl)N=C2C=C1OCC1=CC=CC=C1 WVQSJJCACLCNDS-UHFFFAOYSA-N 0.000 description 4
- WFZJBFVJDDCSKW-UHFFFAOYSA-N 6-bromo-3-[1-(2-chloro-6,7-diethoxyquinazolin-4-yl)piperidin-4-yl]-1-methylquinazoline-2,4-dione Chemical compound O=C1N(C)C2=CC=C(Br)C=C2C(=O)N1C(CC1)CCN1C1=C(C=C(C(OCC)=C2)OCC)C2=NC(Cl)=N1 WFZJBFVJDDCSKW-UHFFFAOYSA-N 0.000 description 4
- YMVRRQSVGUIIFN-UHFFFAOYSA-N 6-chloro-3-[1-(2-chloro-6,7-diethoxyquinazolin-4-yl)piperidin-4-yl]-1h-quinazoline-2,4-dione Chemical compound O=C1NC2=CC=C(Cl)C=C2C(=O)N1C(CC1)CCN1C1=C(C=C(C(OCC)=C2)OCC)C2=NC(Cl)=N1 YMVRRQSVGUIIFN-UHFFFAOYSA-N 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 4
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
- 239000002253 acid Substances 0.000 description 4
- 210000003743 erythrocyte Anatomy 0.000 description 4
- BOQDBLMDEKVDOX-UHFFFAOYSA-N ethyl 4-[(1,6-dimethyl-2,4-dioxoquinazolin-3-yl)methyl]piperidine-1-carboxylate Chemical compound C1CN(C(=O)OCC)CCC1CN1C(=O)C2=CC(C)=CC=C2N(C)C1=O BOQDBLMDEKVDOX-UHFFFAOYSA-N 0.000 description 4
- 229910052751 metal Inorganic materials 0.000 description 4
- 239000002184 metal Chemical class 0.000 description 4
- 239000012044 organic layer Substances 0.000 description 4
- 229910000027 potassium carbonate Inorganic materials 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 3
- UMJFQBXRNAOWGQ-UHFFFAOYSA-N 3-[1-(2-chloro-6,7-diethoxyquinazolin-4-yl)piperidin-4-yl]-6-methyl-1-propylquinazoline-2,4-dione Chemical compound CCOC1=C(OCC)C=C2C(N3CCC(CC3)N3C(=O)C4=CC(C)=CC=C4N(C3=O)CCC)=NC(Cl)=NC2=C1 UMJFQBXRNAOWGQ-UHFFFAOYSA-N 0.000 description 3
- FMGMDYADZGZUQY-UHFFFAOYSA-N 3-[1-(2-chloro-6,7-diethoxyquinazolin-4-yl)piperidin-4-yl]-8-methyl-1h-quinazoline-2,4-dione Chemical compound O=C1NC2=C(C)C=CC=C2C(=O)N1C(CC1)CCN1C1=C(C=C(C(OCC)=C2)OCC)C2=NC(Cl)=N1 FMGMDYADZGZUQY-UHFFFAOYSA-N 0.000 description 3
- FLHVNTUUZKCQOQ-UHFFFAOYSA-N 6-acetyl-3-[1-(2-chloro-6,7-diethoxyquinazolin-4-yl)piperidin-4-yl]-1-methylquinazoline-2,4-dione Chemical compound O=C1N(C)C2=CC=C(C(C)=O)C=C2C(=O)N1C(CC1)CCN1C1=C(C=C(C(OCC)=C2)OCC)C2=NC(Cl)=N1 FLHVNTUUZKCQOQ-UHFFFAOYSA-N 0.000 description 3
- SHFHRMZDTWGPLF-UHFFFAOYSA-N 6-chloro-3-[1-(2-chloro-6,7-diethoxyquinazolin-4-yl)piperidin-4-yl]-1-methylquinazoline-2,4-dione Chemical compound O=C1N(C)C2=CC=C(Cl)C=C2C(=O)N1C(CC1)CCN1C1=C(C=C(C(OCC)=C2)OCC)C2=NC(Cl)=N1 SHFHRMZDTWGPLF-UHFFFAOYSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 3
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- LJOOWESTVASNOG-UFJKPHDISA-N [(1s,3r,4ar,7s,8s,8as)-3-hydroxy-8-[2-[(4r)-4-hydroxy-6-oxooxan-2-yl]ethyl]-7-methyl-1,2,3,4,4a,7,8,8a-octahydronaphthalen-1-yl] (2s)-2-methylbutanoate Chemical compound C([C@H]1[C@@H](C)C=C[C@H]2C[C@@H](O)C[C@@H]([C@H]12)OC(=O)[C@@H](C)CC)CC1C[C@@H](O)CC(=O)O1 LJOOWESTVASNOG-UFJKPHDISA-N 0.000 description 3
- 150000003863 ammonium salts Chemical class 0.000 description 3
- 125000004432 carbon atom Chemical group C* 0.000 description 3
- 238000005119 centrifugation Methods 0.000 description 3
- 229940127204 compound 29 Drugs 0.000 description 3
- 229940126214 compound 3 Drugs 0.000 description 3
- 238000001816 cooling Methods 0.000 description 3
- 150000004292 cyclic ethers Chemical class 0.000 description 3
- ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 3
- PSLIMVZEAPALCD-UHFFFAOYSA-N ethanol;ethoxyethane Chemical compound CCO.CCOCC PSLIMVZEAPALCD-UHFFFAOYSA-N 0.000 description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 3
- 238000010438 heat treatment Methods 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 3
- 239000002244 precipitate Substances 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 3
- 238000006722 reduction reaction Methods 0.000 description 3
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 3
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- 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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- DTTXXNGENPFHHD-UHFFFAOYSA-N n-[2-[1-(2-chloro-6,7-dimethoxyquinazolin-4-yl)piperidin-4-yl]ethyl]-5-methyl-2-nitrobenzamide Chemical compound C=12C=C(OC)C(OC)=CC2=NC(Cl)=NC=1N(CC1)CCC1CCNC(=O)C1=CC(C)=CC=C1[N+]([O-])=O DTTXXNGENPFHHD-UHFFFAOYSA-N 0.000 description 1
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- HFCZAVDJXMNCCU-UHFFFAOYSA-N n-[2-[1-[2-[bis(2-hydroxyethyl)amino]-6,7-dimethoxyquinazolin-4-yl]piperidin-4-yl]ethyl]-5-methyl-2-nitrobenzamide Chemical compound C=12C=C(OC)C(OC)=CC2=NC(N(CCO)CCO)=NC=1N(CC1)CCC1CCNC(=O)C1=CC(C)=CC=C1[N+]([O-])=O HFCZAVDJXMNCCU-UHFFFAOYSA-N 0.000 description 1
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- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
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- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 1
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- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 1
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- 239000000047 product Substances 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
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- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
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- 235000011083 sodium citrates Nutrition 0.000 description 1
- 235000009518 sodium iodide Nutrition 0.000 description 1
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- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
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- BRNULMACUQOKMR-UHFFFAOYSA-N thiomorpholine Chemical compound C1CSCCN1 BRNULMACUQOKMR-UHFFFAOYSA-N 0.000 description 1
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Classifications
-
- 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
- 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
-
- 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
-
- 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
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Public Health (AREA)
- General Chemical & Material Sciences (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Urology & Nephrology (AREA)
- Vascular Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Lubricants (AREA)
- Luminescent Compositions (AREA)
- Fireproofing Substances (AREA)
- Furan Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP6202018A JPH09165385A (ja) | 1994-08-26 | 1994-08-26 | キナゾリン誘導体 |
| PCT/JP1995/001694 WO1996006841A1 (fr) | 1994-08-26 | 1995-08-25 | Derive de quinazoline |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| NO961601D0 NO961601D0 (no) | 1996-04-22 |
| NO961601L NO961601L (no) | 1996-04-22 |
| NO310658B1 true NO310658B1 (no) | 2001-08-06 |
Family
ID=16450565
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO19961601A NO310658B1 (no) | 1994-08-26 | 1996-04-22 | Kinozolinderivater, farmasöytisk preparat inneholdende slike derivater, anvendelse derav, og fremgangsmåte for deresfremstilling |
Country Status (14)
| Country | Link |
|---|---|
| US (1) | US5948784A (de) |
| EP (1) | EP0726267B1 (de) |
| JP (1) | JPH09165385A (de) |
| KR (1) | KR960705810A (de) |
| CN (1) | CN1043991C (de) |
| AT (1) | ATE197710T1 (de) |
| AU (1) | AU689304B2 (de) |
| CA (1) | CA2174854C (de) |
| DE (1) | DE69519469T2 (de) |
| ES (1) | ES2153491T3 (de) |
| FI (1) | FI961758A0 (de) |
| NO (1) | NO310658B1 (de) |
| NZ (1) | NZ291506A (de) |
| WO (1) | WO1996006841A1 (de) |
Families Citing this family (27)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2744451B1 (fr) * | 1996-02-01 | 1998-04-24 | Pf Medicament | Nouvelles imidazolidinones, pyrimidinones, et 1,3-diazepin-2 -ones, leur preparation et leurs applications en therapeutique |
| ATE241985T1 (de) * | 1996-02-19 | 2003-06-15 | Kyowa Hakko Kogyo Kk | Therapeutisches mittel zur behandlung von nierenerkrankungen |
| WO1998033792A1 (fr) * | 1997-01-31 | 1998-08-06 | Kyowa Hakko Kogyo Co., Ltd. | Derives de la piperidine |
| US5866574A (en) * | 1997-04-10 | 1999-02-02 | Kyowa Hakko Kogyo Co., Ltd. | Pancreatitis remedy |
| WO1999019326A1 (fr) * | 1997-10-15 | 1999-04-22 | Kyowa Hakko Kogyo Co., Ltd. | Derives de piperidine |
| AU3344099A (en) * | 1998-04-17 | 1999-11-08 | Kyowa Hakko Kogyo Co. Ltd. | Analgetic agent |
| US6706721B1 (en) | 1998-04-29 | 2004-03-16 | Osi Pharmaceuticals, Inc. | N-(3-ethynylphenylamino)-6,7-bis(2-methoxyethoxy)-4-quinazolinamine mesylate anhydrate and monohydrate |
| US7230000B1 (en) * | 1999-10-27 | 2007-06-12 | Cytokinetics, Incorporated | Methods and compositions utilizing quinazolinones |
| US6545004B1 (en) * | 1999-10-27 | 2003-04-08 | Cytokinetics, Inc. | Methods and compositions utilizing quinazolinones |
| UA74803C2 (uk) | 1999-11-11 | 2006-02-15 | Осі Фармасьютікалз, Інк. | Стійкий поліморф гідрохлориду n-(3-етинілфеніл)-6,7-біс(2-метоксіетокси)-4-хіназолінаміну, спосіб його одержання (варіанти) та фармацевтичне застосування |
| US7087613B2 (en) | 1999-11-11 | 2006-08-08 | Osi Pharmaceuticals, Inc. | Treating abnormal cell growth with a stable polymorph of N-(3-ethynylphenyl)-6,7-bis(2-methoxyethoxy)-4-quinazolinamine hydrochloride |
| EP1480980A4 (de) * | 2002-02-15 | 2005-04-20 | Cytokinetics Inc | Synthesen von quinazolinonen |
| WO2003094839A2 (en) * | 2002-05-09 | 2003-11-20 | Cytokinetics, Inc. | Pyrimidinone compounds, compositions and methods |
| EP1553931A4 (de) | 2002-05-09 | 2006-08-30 | Cytokinetics Inc | Verbindungen, zusammensetzungen und verfahren |
| AU2003290507A1 (en) * | 2002-05-10 | 2004-04-08 | Cytokinetics, Inc. | Compounds, compositions and methods |
| EP1513820A4 (de) * | 2002-05-23 | 2006-09-13 | Cytokinetics Inc | Verbindungen, zusammensetzungen und verfahren |
| AU2003236527A1 (en) * | 2002-06-14 | 2003-12-31 | Cytokinetics, Inc. | Compounds, compositions, and methods |
| WO2004009036A2 (en) * | 2002-07-23 | 2004-01-29 | Cytokinetics, Inc. | Compounds compositions and methods |
| US20040048853A1 (en) * | 2002-08-21 | 2004-03-11 | Gustave Bergnes | Compounds, compositions, and methods |
| WO2004034972A2 (en) * | 2002-09-30 | 2004-04-29 | Cytokinetics, Inc. | Compounds, compositions, and methods |
| WO2004052862A1 (ja) * | 2002-12-10 | 2004-06-24 | Ono Pharmaceutical Co., Ltd. | 含窒素複素環化合物およびその医薬用途 |
| EP1682534A2 (de) * | 2003-11-03 | 2006-07-26 | Cytokinetics, Inc. | Pyrimidin-4-onverbindungen, zusammensetzungen und verfahren |
| WO2005046588A2 (en) * | 2003-11-07 | 2005-05-26 | Cytokinetics, Inc. | Compounds, compositions, and methods |
| JP2007513154A (ja) * | 2003-12-08 | 2007-05-24 | サイトキネティクス・インコーポレーテッド | 化合物、組成物及び方法 |
| EP2520567A3 (de) * | 2006-02-23 | 2012-12-12 | Shionogi & Co., Ltd. | Mit cyclischen Gruppen substituierte, stickstoffhaltige heterocyclische Derivate |
| US9040533B2 (en) | 2012-12-27 | 2015-05-26 | Purdue Pharma L.P. | Oxime-substituted-quinoxaline-type piperidine compounds as ORL-1 modulators |
| EP3028703B1 (de) | 2013-07-29 | 2019-12-04 | Kyowa Kirin Co., Ltd. | Piperidin abkömmlinge als wnt-signalisierungsinhibitor |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CH583225A5 (de) * | 1972-09-25 | 1976-12-31 | Sandoz Ag | |
| US5296487A (en) * | 1990-01-02 | 1994-03-22 | Fujisawa Pharmaceutical Co., Ltd. | Quinazoline derivatives and their preparation |
| US5624926A (en) * | 1993-02-18 | 1997-04-29 | Kyowa Hakko Kogyo Co., Ltd. | Piperidinyl-dioxoquinazolines as adenosine reuptake inhibitors |
-
1994
- 1994-08-26 JP JP6202018A patent/JPH09165385A/ja active Pending
-
1995
- 1995-08-25 ES ES95929231T patent/ES2153491T3/es not_active Expired - Lifetime
- 1995-08-25 CA CA002174854A patent/CA2174854C/en not_active Expired - Fee Related
- 1995-08-25 KR KR1019960702161A patent/KR960705810A/ko active IP Right Grant
- 1995-08-25 CN CN95190792A patent/CN1043991C/zh not_active Expired - Fee Related
- 1995-08-25 EP EP95929231A patent/EP0726267B1/de not_active Expired - Lifetime
- 1995-08-25 AT AT95929231T patent/ATE197710T1/de not_active IP Right Cessation
- 1995-08-25 DE DE69519469T patent/DE69519469T2/de not_active Expired - Fee Related
- 1995-08-25 AU AU32655/95A patent/AU689304B2/en not_active Ceased
- 1995-08-25 NZ NZ291506A patent/NZ291506A/en unknown
- 1995-08-25 WO PCT/JP1995/001694 patent/WO1996006841A1/ja active IP Right Grant
-
1996
- 1996-04-22 NO NO19961601A patent/NO310658B1/no not_active IP Right Cessation
- 1996-04-24 FI FI961758A patent/FI961758A0/fi unknown
-
1998
- 1998-06-03 US US09/089,255 patent/US5948784A/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| DE69519469D1 (de) | 2000-12-28 |
| NO961601D0 (no) | 1996-04-22 |
| CA2174854C (en) | 2001-11-20 |
| EP0726267B1 (de) | 2000-11-22 |
| CN1134150A (zh) | 1996-10-23 |
| ES2153491T3 (es) | 2001-03-01 |
| JPH09165385A (ja) | 1997-06-24 |
| NZ291506A (en) | 1997-03-24 |
| CA2174854A1 (en) | 1996-03-07 |
| KR960705810A (ko) | 1996-11-08 |
| AU3265595A (en) | 1996-03-22 |
| EP0726267A1 (de) | 1996-08-14 |
| DE69519469T2 (de) | 2001-07-26 |
| US5948784A (en) | 1999-09-07 |
| CN1043991C (zh) | 1999-07-07 |
| EP0726267A4 (de) | 1996-12-11 |
| ATE197710T1 (de) | 2000-12-15 |
| FI961758A (fi) | 1996-04-24 |
| NO961601L (no) | 1996-04-22 |
| FI961758A0 (fi) | 1996-04-24 |
| AU689304B2 (en) | 1998-03-26 |
| WO1996006841A1 (fr) | 1996-03-07 |
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| MM1K | Lapsed by not paying the annual fees |
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