NO319832B1 - Pyridazin-3-on-derivater og medikamenter inneholdende disse samt anvendelse av derivatene. - Google Patents
Pyridazin-3-on-derivater og medikamenter inneholdende disse samt anvendelse av derivatene. Download PDFInfo
- Publication number
- NO319832B1 NO319832B1 NO20014099A NO20014099A NO319832B1 NO 319832 B1 NO319832 B1 NO 319832B1 NO 20014099 A NO20014099 A NO 20014099A NO 20014099 A NO20014099 A NO 20014099A NO 319832 B1 NO319832 B1 NO 319832B1
- Authority
- NO
- Norway
- Prior art keywords
- pyridazin
- group
- bis
- methoxyphenyl
- derivative
- Prior art date
Links
- AAILEWXSEQLMNI-UHFFFAOYSA-N 1h-pyridazin-6-one Chemical class OC1=CC=CN=N1 AAILEWXSEQLMNI-UHFFFAOYSA-N 0.000 title claims abstract description 30
- 239000003814 drug Substances 0.000 title claims abstract description 23
- 229940079593 drug Drugs 0.000 title claims abstract description 13
- 150000003839 salts Chemical class 0.000 claims abstract description 22
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 15
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 15
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims abstract description 8
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 6
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims abstract description 6
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims abstract description 5
- 125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 5
- 238000002360 preparation method Methods 0.000 claims description 55
- 230000015572 biosynthetic process Effects 0.000 claims description 25
- 201000010099 disease Diseases 0.000 claims description 13
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 13
- 102000000589 Interleukin-1 Human genes 0.000 claims description 12
- 108010002352 Interleukin-1 Proteins 0.000 claims description 12
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 7
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 7
- 125000004432 carbon atom Chemical group C* 0.000 claims description 6
- 208000023589 ischemic disease Diseases 0.000 claims description 6
- 229940124597 therapeutic agent Drugs 0.000 claims description 6
- 125000005843 halogen group Chemical group 0.000 claims description 5
- 210000000987 immune system Anatomy 0.000 claims description 5
- 208000027866 inflammatory disease Diseases 0.000 claims description 5
- 230000002757 inflammatory effect Effects 0.000 claims description 5
- 230000003449 preventive effect Effects 0.000 claims description 5
- 230000000638 stimulation Effects 0.000 claims description 5
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 4
- XEACZWOCRMMPEM-UHFFFAOYSA-N ethyl 2-benzyl-5,6-bis(4-methoxyphenyl)-3-oxopyridazine-4-carboxylate Chemical compound C=1C=C(OC)C=CC=1C1=NN(CC=2C=CC=CC=2)C(=O)C(C(=O)OCC)=C1C1=CC=C(OC)C=C1 XEACZWOCRMMPEM-UHFFFAOYSA-N 0.000 claims description 4
- 239000003112 inhibitor Substances 0.000 claims description 4
- 125000005544 phthalimido group Chemical group 0.000 claims description 4
- VFQPTGJHJFVHNI-UHFFFAOYSA-N 2-(cyclopentylmethyl)-5,6-bis(4-methoxyphenyl)-3-oxopyridazine-4-carbonitrile Chemical compound C1=CC(OC)=CC=C1C(C(=C(C#N)C1=O)C=2C=CC(OC)=CC=2)=NN1CC1CCCC1 VFQPTGJHJFVHNI-UHFFFAOYSA-N 0.000 claims description 3
- DTHGSNMGHKXXAK-UHFFFAOYSA-N 2-ethyl-5,6-bis(4-methoxyphenyl)-3-oxopyridazine-4-carbonitrile Chemical compound C=1C=C(OC)C=CC=1C1=C(C#N)C(=O)N(CC)N=C1C1=CC=C(OC)C=C1 DTHGSNMGHKXXAK-UHFFFAOYSA-N 0.000 claims description 3
- 208000001132 Osteoporosis Diseases 0.000 claims description 3
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- 206010009887 colitis Diseases 0.000 claims description 3
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- 238000011282 treatment Methods 0.000 claims description 3
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 2
- PNZNGDWSNAZHII-UHFFFAOYSA-N 2-(cyclopropylmethyl)-5,6-bis(4-methoxyphenyl)-3-oxopyridazine-4-carbonitrile Chemical compound C1=CC(OC)=CC=C1C(C(=C(C#N)C1=O)C=2C=CC(OC)=CC=2)=NN1CC1CC1 PNZNGDWSNAZHII-UHFFFAOYSA-N 0.000 claims description 2
- DCNIJNXEKXPKML-UHFFFAOYSA-N 2-(cyclopropylmethyl)-5,6-bis(4-methoxyphenyl)-3-oxopyridazine-4-carboxamide Chemical compound C1=CC(OC)=CC=C1C(C(=C(C(N)=O)C1=O)C=2C=CC(OC)=CC=2)=NN1CC1CC1 DCNIJNXEKXPKML-UHFFFAOYSA-N 0.000 claims description 2
- RFKWMKNONHRUKU-UHFFFAOYSA-N 2-[[5,6-bis(4-methoxyphenyl)-2-(2-methylpropyl)-3-oxopyridazin-4-yl]methyl]isoindole-1,3-dione Chemical compound C1=CC(OC)=CC=C1C1=NN(CC(C)C)C(=O)C(CN2C(C3=CC=CC=C3C2=O)=O)=C1C1=CC=C(OC)C=C1 RFKWMKNONHRUKU-UHFFFAOYSA-N 0.000 claims description 2
- 125000005036 alkoxyphenyl group Chemical group 0.000 claims description 2
- PGJCOGMDQWETAK-UHFFFAOYSA-N ethyl 5,6-bis(4-methoxyphenyl)-3-oxo-2-propan-2-ylpyridazine-4-carboxylate Chemical compound C=1C=C(OC)C=CC=1C1=NN(C(C)C)C(=O)C(C(=O)OCC)=C1C1=CC=C(OC)C=C1 PGJCOGMDQWETAK-UHFFFAOYSA-N 0.000 claims description 2
- 229910052736 halogen Inorganic materials 0.000 claims description 2
- 150000002367 halogens Chemical class 0.000 claims description 2
- 125000004076 pyridyl group Chemical group 0.000 claims description 2
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 1
- 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims 1
- 150000001875 compounds Chemical class 0.000 abstract description 87
- 230000000694 effects Effects 0.000 abstract description 6
- 239000004615 ingredient Substances 0.000 abstract description 5
- 125000001424 substituent group Chemical group 0.000 abstract description 4
- 125000003118 aryl group Chemical group 0.000 abstract description 2
- 125000004122 cyclic group Chemical group 0.000 abstract description 2
- 230000019189 interleukin-1 beta production Effects 0.000 abstract 1
- 238000002844 melting Methods 0.000 description 40
- 230000008018 melting Effects 0.000 description 40
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 39
- 238000000034 method Methods 0.000 description 39
- 239000007858 starting material Substances 0.000 description 34
- 238000005160 1H NMR spectroscopy Methods 0.000 description 33
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 30
- 239000002904 solvent Substances 0.000 description 29
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 27
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 21
- LOGFVTREOLYCPF-KXNHARMFSA-N (2s,3r)-2-[[(2r)-1-[(2s)-2,6-diaminohexanoyl]pyrrolidine-2-carbonyl]amino]-3-hydroxybutanoic acid Chemical compound C[C@@H](O)[C@@H](C(O)=O)NC(=O)[C@H]1CCCN1C(=O)[C@@H](N)CCCCN LOGFVTREOLYCPF-KXNHARMFSA-N 0.000 description 17
- 102000003777 Interleukin-1 beta Human genes 0.000 description 17
- 108090000193 Interleukin-1 beta Proteins 0.000 description 17
- OQNGCCWBHLEQFN-UHFFFAOYSA-N chloroform;hexane Chemical compound ClC(Cl)Cl.CCCCCC OQNGCCWBHLEQFN-UHFFFAOYSA-N 0.000 description 17
- 230000002401 inhibitory effect Effects 0.000 description 16
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 14
- TVPRCLHSULCNLV-UHFFFAOYSA-N pyridazin-3-one Chemical compound O=C1C=CC=N[N]1 TVPRCLHSULCNLV-UHFFFAOYSA-N 0.000 description 13
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 12
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 12
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
- 238000006243 chemical reaction Methods 0.000 description 12
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 12
- -1 cyano-substituted pyridazin-3-one Chemical class 0.000 description 11
- 238000003756 stirring Methods 0.000 description 10
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 10
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 9
- ASYKDWXBQYCRBA-UHFFFAOYSA-N 3,4-bis(4-methoxyphenyl)-6-oxo-1h-pyridazine-5-carbonitrile Chemical compound C1=CC(OC)=CC=C1C1=NNC(=O)C(C#N)=C1C1=CC=C(OC)C=C1 ASYKDWXBQYCRBA-UHFFFAOYSA-N 0.000 description 9
- 239000011541 reaction mixture Substances 0.000 description 9
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- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 8
- OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 8
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 8
- 238000005481 NMR spectroscopy Methods 0.000 description 7
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 7
- 238000000605 extraction Methods 0.000 description 7
- JPELSVPGJBLDQI-UHFFFAOYSA-N 5,6-bis(4-methoxyphenyl)-2-(2-methylpropyl)-3-oxopyridazine-4-carboxylic acid Chemical compound C1=CC(OC)=CC=C1C1=NN(CC(C)C)C(=O)C(C(O)=O)=C1C1=CC=C(OC)C=C1 JPELSVPGJBLDQI-UHFFFAOYSA-N 0.000 description 6
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- 239000007864 aqueous solution Substances 0.000 description 6
- 229910000027 potassium carbonate Inorganic materials 0.000 description 6
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 6
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 5
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 5
- SRCZQMGIVIYBBJ-UHFFFAOYSA-N ethoxyethane;ethyl acetate Chemical compound CCOCC.CCOC(C)=O SRCZQMGIVIYBBJ-UHFFFAOYSA-N 0.000 description 5
- 238000004519 manufacturing process Methods 0.000 description 5
- 239000000203 mixture Substances 0.000 description 5
- 239000000741 silica gel Substances 0.000 description 5
- 229910002027 silica gel Inorganic materials 0.000 description 5
- 235000011121 sodium hydroxide Nutrition 0.000 description 5
- YPIRRKUYXQIVIS-UHFFFAOYSA-N 2-(cyclopropylmethyl)-5,6-bis(4-methoxyphenyl)-3-oxopyridazine-4-carboxylic acid Chemical compound C1=CC(OC)=CC=C1C(C(=C(C(O)=O)C1=O)C=2C=CC(OC)=CC=2)=NN1CC1CC1 YPIRRKUYXQIVIS-UHFFFAOYSA-N 0.000 description 4
- YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 4
- 150000008065 acid anhydrides Chemical class 0.000 description 4
- QSKWJTXWJJOJFP-UHFFFAOYSA-N chloroform;ethoxyethane Chemical compound ClC(Cl)Cl.CCOCC QSKWJTXWJJOJFP-UHFFFAOYSA-N 0.000 description 4
- NQMRYBIKMRVZLB-UHFFFAOYSA-N methylamine hydrochloride Chemical compound [Cl-].[NH3+]C NQMRYBIKMRVZLB-UHFFFAOYSA-N 0.000 description 4
- 238000003786 synthesis reaction Methods 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 3
- NONLSZJSZYMEQQ-UHFFFAOYSA-N 2-benzyl-5,6-bis(4-methoxyphenyl)-3-oxopyridazine-4-carboxylic acid Chemical compound C1=CC(OC)=CC=C1C(C(=C(C(O)=O)C1=O)C=2C=CC(OC)=CC=2)=NN1CC1=CC=CC=C1 NONLSZJSZYMEQQ-UHFFFAOYSA-N 0.000 description 3
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
- 210000004027 cell Anatomy 0.000 description 3
- 239000013078 crystal Substances 0.000 description 3
- 239000003480 eluent Substances 0.000 description 3
- HOBJKRXPDGMGGC-UHFFFAOYSA-N ethyl 3,4-bis(4-methoxyphenyl)-6-oxo-1h-pyridazine-5-carboxylate Chemical compound C=1C=C(OC)C=CC=1C1=NNC(=O)C(C(=O)OCC)=C1C1=CC=C(OC)C=C1 HOBJKRXPDGMGGC-UHFFFAOYSA-N 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
- FYRHIOVKTDQVFC-UHFFFAOYSA-M potassium phthalimide Chemical compound [K+].C1=CC=C2C(=O)[N-]C(=O)C2=C1 FYRHIOVKTDQVFC-UHFFFAOYSA-M 0.000 description 3
- 238000004237 preparative chromatography Methods 0.000 description 3
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 3
- 229920006395 saturated elastomer Polymers 0.000 description 3
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 3
- 239000012453 solvate Substances 0.000 description 3
- JHFAEUICJHBVHB-UHFFFAOYSA-N 1h-indol-2-ol Chemical class C1=CC=C2NC(O)=CC2=C1 JHFAEUICJHBVHB-UHFFFAOYSA-N 0.000 description 2
- LZJLXDNGANKYIE-UHFFFAOYSA-N 3,4-diphenylpyridazine Chemical class C1=CC=CC=C1C1=CC=NN=C1C1=CC=CC=C1 LZJLXDNGANKYIE-UHFFFAOYSA-N 0.000 description 2
- BUJYYXIMVSQQMR-UHFFFAOYSA-N 5,6-bis(4-methoxyphenyl)-3-oxo-2-propan-2-ylpyridazine-4-carboxylic acid Chemical compound C1=CC(OC)=CC=C1C1=NN(C(C)C)C(=O)C(C(O)=O)=C1C1=CC=C(OC)C=C1 BUJYYXIMVSQQMR-UHFFFAOYSA-N 0.000 description 2
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 2
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 2
- 102000004127 Cytokines Human genes 0.000 description 2
- 108090000695 Cytokines Proteins 0.000 description 2
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- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 2
- 102000019223 Interleukin-1 receptor Human genes 0.000 description 2
- 108050006617 Interleukin-1 receptor Proteins 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 150000004703 alkoxides Chemical class 0.000 description 2
- KCXMKQUNVWSEMD-UHFFFAOYSA-N benzyl chloride Chemical compound ClCC1=CC=CC=C1 KCXMKQUNVWSEMD-UHFFFAOYSA-N 0.000 description 2
- 229940073608 benzyl chloride Drugs 0.000 description 2
- WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 2
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- 238000004587 chromatography analysis Methods 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
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- IQDGSYLLQPDQDV-UHFFFAOYSA-N dimethylazanium;chloride Chemical compound Cl.CNC IQDGSYLLQPDQDV-UHFFFAOYSA-N 0.000 description 2
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- RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
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- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 2
- 150000007529 inorganic bases Chemical class 0.000 description 2
- 229910052740 iodine Inorganic materials 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 239000002609 medium Substances 0.000 description 2
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- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 2
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- 229910000033 sodium borohydride Inorganic materials 0.000 description 2
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- 239000000126 substance Substances 0.000 description 2
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- CYNYIHKIEHGYOZ-UHFFFAOYSA-N 1-bromopropane Chemical compound CCCBr CYNYIHKIEHGYOZ-UHFFFAOYSA-N 0.000 description 1
- VFWCMGCRMGJXDK-UHFFFAOYSA-N 1-chlorobutane Chemical compound CCCCCl VFWCMGCRMGJXDK-UHFFFAOYSA-N 0.000 description 1
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 1
- PGZVFRAEAAXREB-UHFFFAOYSA-N 2,2-dimethylpropanoyl 2,2-dimethylpropanoate Chemical compound CC(C)(C)C(=O)OC(=O)C(C)(C)C PGZVFRAEAAXREB-UHFFFAOYSA-N 0.000 description 1
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D237/00—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings
- C07D237/02—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings not condensed with other rings
- C07D237/06—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
- C07D237/10—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D237/24—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D237/00—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings
- C07D237/02—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings not condensed with other rings
- C07D237/06—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
- C07D237/10—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D237/14—Oxygen atoms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/50—Pyridazines; Hydrogenated pyridazines
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
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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
-
- 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
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
- A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
-
- 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
- A61P37/00—Drugs for immunological or allergic disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Engineering & Computer Science (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Immunology (AREA)
- Physical Education & Sports Medicine (AREA)
- Rheumatology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Vascular Medicine (AREA)
- Pain & Pain Management (AREA)
- Transplantation (AREA)
- Urology & Nephrology (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Saccharide Compounds (AREA)
- Fats And Perfumes (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP11049758A JP2000247959A (ja) | 1999-02-26 | 1999-02-26 | ピリダジン−３−オン誘導体及びこれを含有する医薬 |
| PCT/JP2000/001098 WO2000050408A1 (fr) | 1999-02-26 | 2000-02-25 | Derives de pyridazin-3-one et medicaments contenant ces derives |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| NO20014099D0 NO20014099D0 (no) | 2001-08-23 |
| NO20014099L NO20014099L (no) | 2001-10-23 |
| NO319832B1 true NO319832B1 (no) | 2005-09-19 |
Family
ID=12840099
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO20014099A NO319832B1 (no) | 1999-02-26 | 2001-08-23 | Pyridazin-3-on-derivater og medikamenter inneholdende disse samt anvendelse av derivatene. |
Country Status (18)
| Country | Link |
|---|---|
| US (1) | US6680316B1 (de) |
| EP (1) | EP1156039B1 (de) |
| JP (2) | JP2000247959A (de) |
| KR (1) | KR100647726B1 (de) |
| CN (1) | CN1148355C (de) |
| AT (1) | ATE305926T1 (de) |
| AU (1) | AU764393B2 (de) |
| CA (1) | CA2364801C (de) |
| DE (1) | DE60022986T2 (de) |
| DK (1) | DK1156039T3 (de) |
| ES (1) | ES2250100T3 (de) |
| HK (1) | HK1044534B (de) |
| HU (1) | HUP0200088A3 (de) |
| NO (1) | NO319832B1 (de) |
| NZ (1) | NZ513578A (de) |
| RU (1) | RU2232755C2 (de) |
| TW (1) | TWI249533B (de) |
| WO (1) | WO2000050408A1 (de) |
Families Citing this family (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1142148C (zh) * | 1997-11-19 | 2004-03-17 | 兴和株式会社 | 新颖的哒嗪衍生物和含有其作为有效成分的药物 |
| ATE425148T1 (de) * | 2000-09-18 | 2009-03-15 | Eisai R&D Man Co Ltd | Triazinone sowie deren medizinale anwendung |
| AU761191B2 (en) * | 2001-05-24 | 2003-05-29 | Pfizer Products Inc. | Therapies for tissue damage resulting from ischemia |
| KR20040039377A (ko) * | 2001-09-26 | 2004-05-10 | 코와 가부시키가이샤 | 수용성 페닐피리다진 유도체 및 이를 함유하는 의약 |
| WO2004078751A1 (ja) * | 2003-03-07 | 2004-09-16 | Kowa Co., Ltd. | ベンゾフラン誘導体 |
| CN1759103A (zh) * | 2003-03-18 | 2006-04-12 | 兴和株式会社 | 水溶性苯基哒嗪衍生物及含有该衍生物的医药品 |
| EP1628665A2 (de) * | 2003-04-16 | 2006-03-01 | Amgen Inc. | 3-phenyl-4-(pyrimidin-2-yl)-6-(piperidin-4-yl) derivate und verwandte verbindungen als tnf-alpha und il-1 inhibitoren zur behandlung von entzündlichen erkrankungen |
| WO2007044796A2 (en) * | 2005-10-11 | 2007-04-19 | Nps Pharmaceuticals, Inc. | Pyridazinone compounds as calcilytics |
| JPWO2007049732A1 (ja) * | 2005-10-28 | 2009-04-30 | 興和株式会社 | 関節リウマチの予防及び／又は治療法 |
| EP2953944B1 (de) * | 2013-02-07 | 2017-04-26 | Merck Patent GmbH | Pyridazinonamidderivate |
| MX2017009624A (es) * | 2015-02-06 | 2017-11-20 | Merck Patent Gmbh | Macrociclos de piridazinona como inhibidores de cinasas asociadas al receptor de interleucina 1(irak) y sus usos. |
| FR3103701B1 (fr) * | 2019-11-28 | 2021-11-26 | Inst Nat Sante Rech Med | Composés de typen2-arylméthyl-4-haloalkyl-pyridazin-3-one et leur utilisation |
| UY39082A (es) * | 2020-02-14 | 2021-09-30 | Fmc Corp | Piridazinonas fungicidas |
Family Cites Families (17)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2839532A (en) * | 1958-06-17 | Pyridazone compounds and process of | ||
| GB788393A (en) * | 1953-04-30 | 1958-01-02 | Ciba Ltd | Process for the manufacture of pyridazone compounds |
| US3840597A (en) | 1971-02-24 | 1974-10-08 | Riker Laboratories Inc | Substituted 2-phenoxy alkane-sulfonanilides |
| AR206496A1 (es) | 1972-07-03 | 1976-07-30 | Riker Laboratories Inc | Procedimiento para la preparacion de 2-fenoxi-4-nitro-alquil o haloalquilsulfonanilidas |
| US4238490A (en) * | 1979-02-12 | 1980-12-09 | Diamond Shamrock Corporation | Antihypertensive pyridazin(2H)-3-ones |
| JPS57501328A (de) * | 1980-08-07 | 1982-07-29 | ||
| US4545810A (en) | 1980-08-07 | 1985-10-08 | Sds Biotech Corporation | Herbicidal and plant growth regulant diphenylpyridazinones |
| JPH0753725B2 (ja) | 1987-10-08 | 1995-06-07 | 富山化学工業株式会社 | ４ｈ―１―ベンゾピラン―４―オン誘導体およびその塩、それらの製造法並びにそれらを含有する抗炎症剤 |
| FI91062C (fi) | 1988-12-28 | 1994-05-10 | Eisai Co Ltd | Menetelmä lääkeaineena käyttökelpoisten naftaleenijohdannaisten valmistamiseksi |
| MX9300141A (es) | 1992-01-13 | 1994-07-29 | Smithkline Beecham Corp | Compuestos de imidazol novedosos, procedimiento para su preparacion y composiciones farmaceuticas que lo contienen. |
| DE69408598T2 (de) * | 1993-06-08 | 1998-09-17 | Vertex Pharmaceuticals Inc Cam | Pyridazine als Interleukin-1-beta Verwandlungsenzym Inhibitoren |
| EP0871444A4 (de) | 1995-08-10 | 1999-01-13 | Merck & Co Inc | 2,5 substituierte aryl pyrrol, dieses enthaltende zusammensetzungen und dessen verwendung |
| CA2294548A1 (en) | 1997-08-22 | 1999-03-04 | Abbott Laboratories | Pyridazinones as prostaglandin endoperoxide h synthase biosynthesis inhibitors |
| WO1999010331A1 (en) | 1997-08-22 | 1999-03-04 | Abbott Laboratories | Arylpyridazinones as prostaglandin endoperoxide h synthase biosynthesis inhibitors |
| CN1142148C (zh) | 1997-11-19 | 2004-03-17 | 兴和株式会社 | 新颖的哒嗪衍生物和含有其作为有效成分的药物 |
| TWI241295B (en) | 1998-03-02 | 2005-10-11 | Kowa Co | Pyridazine derivative and medicine containing the same as effect component |
| CN1279026C (zh) | 1998-10-27 | 2006-10-11 | 艾博特公司 | 前列腺素内过氧化物h合酶生物合成抑制剂 |
-
1999
- 1999-02-26 JP JP11049758A patent/JP2000247959A/ja active Pending
-
2000
- 2000-02-25 AT AT00905344T patent/ATE305926T1/de not_active IP Right Cessation
- 2000-02-25 DE DE60022986T patent/DE60022986T2/de not_active Expired - Lifetime
- 2000-02-25 US US09/926,040 patent/US6680316B1/en not_active Expired - Fee Related
- 2000-02-25 TW TW089103388A patent/TWI249533B/zh not_active IP Right Cessation
- 2000-02-25 RU RU2001126063/04A patent/RU2232755C2/ru active
- 2000-02-25 DK DK00905344T patent/DK1156039T3/da active
- 2000-02-25 AU AU26928/00A patent/AU764393B2/en not_active Ceased
- 2000-02-25 NZ NZ513578A patent/NZ513578A/en not_active Application Discontinuation
- 2000-02-25 JP JP2000600991A patent/JP4456765B2/ja not_active Expired - Fee Related
- 2000-02-25 HU HU0200088A patent/HUP0200088A3/hu unknown
- 2000-02-25 CA CA002364801A patent/CA2364801C/en not_active Expired - Fee Related
- 2000-02-25 WO PCT/JP2000/001098 patent/WO2000050408A1/ja active IP Right Grant
- 2000-02-25 KR KR1020017009829A patent/KR100647726B1/ko not_active IP Right Cessation
- 2000-02-25 CN CNB00804242XA patent/CN1148355C/zh not_active Expired - Fee Related
- 2000-02-25 EP EP00905344A patent/EP1156039B1/de not_active Expired - Lifetime
- 2000-02-25 ES ES00905344T patent/ES2250100T3/es not_active Expired - Lifetime
-
2001
- 2001-08-23 NO NO20014099A patent/NO319832B1/no not_active IP Right Cessation
-
2002
- 2002-08-20 HK HK02106060.0A patent/HK1044534B/zh not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| CA2364801C (en) | 2009-05-19 |
| NO20014099D0 (no) | 2001-08-23 |
| AU764393B2 (en) | 2003-08-14 |
| TWI249533B (en) | 2006-02-21 |
| NZ513578A (en) | 2005-04-29 |
| HK1044534A1 (en) | 2002-10-25 |
| WO2000050408A1 (fr) | 2000-08-31 |
| NO20014099L (no) | 2001-10-23 |
| US6680316B1 (en) | 2004-01-20 |
| HUP0200088A2 (hu) | 2002-11-28 |
| DE60022986T2 (de) | 2006-05-11 |
| CA2364801A1 (en) | 2000-08-31 |
| ES2250100T3 (es) | 2006-04-16 |
| EP1156039B1 (de) | 2005-10-05 |
| DE60022986D1 (de) | 2006-02-16 |
| JP2000247959A (ja) | 2000-09-12 |
| CN1148355C (zh) | 2004-05-05 |
| CN1341103A (zh) | 2002-03-20 |
| KR100647726B1 (ko) | 2006-11-23 |
| HUP0200088A3 (en) | 2002-12-28 |
| EP1156039A4 (de) | 2002-04-17 |
| AU2692800A (en) | 2000-09-14 |
| HK1044534B (zh) | 2004-12-10 |
| ATE305926T1 (de) | 2005-10-15 |
| DK1156039T3 (da) | 2006-01-30 |
| RU2232755C2 (ru) | 2004-07-20 |
| JP4456765B2 (ja) | 2010-04-28 |
| EP1156039A1 (de) | 2001-11-21 |
| KR20010101979A (ko) | 2001-11-15 |
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Legal Events
| Date | Code | Title | Description |
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| MM1K | Lapsed by not paying the annual fees |