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 PDF

Info

Publication number: NO319832B1
Authority: NO; Norway
Prior art keywords: pyridazin; group; bis; methoxyphenyl; derivative
Prior art date: 1999-02-26

Application number

NO20014099A

Other languages

English (en)

Norwegian (no)

Other versions

NO20014099D0 (no

NO20014099L (no

Inventor

Hiromichi Shigyo

Masao Ohkuchi

Yoshinori Kyotani

Tomoyuki Koshi

Takahiro Kitamura

Takayuki Matsuda

Hideo Yoshizaki

Kyoko Yasuoka

Tomoko Furuyama

Original Assignee

Kowa Co

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

1999-02-26

Filing date

2001-08-23

Publication date

2005-09-19

2001-08-23 Application filed by Kowa Co filed Critical Kowa Co

2001-08-23 Publication of NO20014099D0 publication Critical patent/NO20014099D0/no

2001-10-23 Publication of NO20014099L publication Critical patent/NO20014099L/no

2005-09-19 Publication of NO319832B1 publication Critical patent/NO319832B1/no

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
206010040047 Sepsis Diseases 0.000 claims description 3
239000004480 active ingredient Substances 0.000 claims description 3
206010003246 arthritis Diseases 0.000 claims description 3
206010009887 colitis Diseases 0.000 claims description 3
239000003937 drug carrier Substances 0.000 claims description 3
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 3
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
239000000243 solution Substances 0.000 description 9
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
102000004190 Enzymes Human genes 0.000 description 2
108090000790 Enzymes Proteins 0.000 description 2
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
239000011230 binding agent Substances 0.000 description 2
239000003518 caustics Substances 0.000 description 2
239000003795 chemical substances by application Substances 0.000 description 2
SKCNIGRBPJIUBQ-UHFFFAOYSA-N chloroform;ethyl acetate Chemical compound ClC(Cl)Cl.CCOC(C)=O SKCNIGRBPJIUBQ-UHFFFAOYSA-N 0.000 description 2
ZVTQWXCKQTUVPY-UHFFFAOYSA-N chloromethylcyclopropane Chemical compound ClCC1CC1 ZVTQWXCKQTUVPY-UHFFFAOYSA-N 0.000 description 2
238000004587 chromatography analysis Methods 0.000 description 2
238000001816 cooling Methods 0.000 description 2
XHFGWHUWQXTGAT-UHFFFAOYSA-N dimethylamine hydrochloride Natural products CNC(C)C XHFGWHUWQXTGAT-UHFFFAOYSA-N 0.000 description 2
IQDGSYLLQPDQDV-UHFFFAOYSA-N dimethylazanium;chloride Chemical compound Cl.CNC IQDGSYLLQPDQDV-UHFFFAOYSA-N 0.000 description 2
229940088598 enzyme Drugs 0.000 description 2
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
150000004820 halides Chemical class 0.000 description 2
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
229910052751 metal Inorganic materials 0.000 description 2
239000002184 metal Substances 0.000 description 2
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 2
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
150000007530 organic bases Chemical class 0.000 description 2
CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 2
239000000546 pharmaceutical excipient Substances 0.000 description 2
239000000843 powder Substances 0.000 description 2
238000001953 recrystallisation Methods 0.000 description 2
238000010992 reflux Methods 0.000 description 2
238000011160 research Methods 0.000 description 2
229910000033 sodium borohydride Inorganic materials 0.000 description 2
239000012279 sodium borohydride Substances 0.000 description 2
229910000029 sodium carbonate Inorganic materials 0.000 description 2
239000011780 sodium chloride Substances 0.000 description 2
239000000126 substance Substances 0.000 description 2
HFRXJVQOXRXOPP-UHFFFAOYSA-N thionyl bromide Chemical compound BrS(Br)=O HFRXJVQOXRXOPP-UHFFFAOYSA-N 0.000 description 2
HLVFKOKELQSXIQ-UHFFFAOYSA-N 1-bromo-2-methylpropane Chemical compound CC(C)CBr HLVFKOKELQSXIQ-UHFFFAOYSA-N 0.000 description 1
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

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
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- 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
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- 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
- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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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
- A—HUMAN NECESSITIES
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- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
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- 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

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Bioinformatics & Cheminformatics (AREA)
Veterinary Medicine (AREA)
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NO20014099A 1999-02-26 2001-08-23 Pyridazin-3-on-derivater og medikamenter inneholdende disse samt anvendelse av derivatene. NO319832B1 (no)

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 (en)	1999-02-26	2000-02-25	Pyridazin-3-one derivatives and medicines containing the same

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

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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)

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KR100770327B1 (ko) *	2000-09-18	2007-10-25	에자이 알앤드디 매니지먼트 가부시키가이샤	피리다지논 및 트리아지논 화합물류 및 그들의 의약 용도
AU761191B2 (en) *	2001-05-24	2003-05-29	Pfizer Products Inc.	Therapies for tissue damage resulting from ischemia
US6869954B2 (en) *	2001-09-26	2005-03-22	Kowa Co., Ltd.	Water-soluble phenylpyridazine compounds and compositions containing the same
BRPI0407519A (pt) *	2003-03-07	2006-02-14	Kowa Co	derivados de benzofurano
RU2005132167A (ru)	2003-03-18	2006-05-10	Кова Ко., Лтд. (Jp)	Водорастворимые производные фенилпиридазина и лекарственные средства, содержащие их
US20040254178A1 (en) *	2003-04-16	2004-12-16	Amgen Inc.	Substituted heterocyclic compounds and methods of use
ES2251866B1 (es) *	2004-06-18	2007-06-16	Laboratorios Almirall S.A.	Nuevos derivados de piridazin-3(2h)-ona.
WO2007044796A2 (en) *	2005-10-11	2007-04-19	Nps Pharmaceuticals, Inc.	Pyridazinone compounds as calcilytics
US20090131443A1 (en) *	2005-10-28	2009-05-21	Kowa Co., Ltd.	Method for prevention and/or treatment of rheumatoid arthritis
HUE032863T2 (en) *	2013-02-07	2017-11-28	Merck Patent Gmbh	Piridazinonamid derivatives
US9624246B2 (en) *	2015-02-06	2017-04-18	Merck Patent Gmbh	Pyridazinone macrocycles as IRAK inhibitors and uses thereof
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
PH12022552069A1 (en) *	2020-02-14	2024-02-12	Fmc Corp	Substituted 5,6-diphenyl-3(2h)-pyridazinones for use as fungicides

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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.
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DK1005460T3 (da)	1997-08-22	2006-07-10	Abbott Lab	Inhibitorer af biosyntesen af prostaglandin-endoperoxid H-synthase
CA2299300C (en)	1997-08-22	2007-04-17	Abbott Laboratories	Arylpyridazinones as prostaglandin endoperoxide h synthase bisoynthesis inhibitors
US6348468B1 (en)	1997-11-19	2002-02-19	Kowa Co., Ltd.	Pyridazine compounds and compositions containing the same
TWI241295B (en)	1998-03-02	2005-10-11	Kowa Co	Pyridazine derivative and medicine containing the same as effect component
TR200101765T2 (tr)	1998-10-27	2002-02-21	Abbott Laboratories	Prostaglandin endoperoksit H sentaz biyosentez inhibitörleri

1999
- 1999-02-26 JP JP11049758A patent/JP2000247959A/ja active Pending
2000
- 2000-02-25 HK HK02106060.0A patent/HK1044534B/zh not_active IP Right Cessation
- 2000-02-25 CN CNB00804242XA patent/CN1148355C/zh not_active Expired - Fee Related
- 2000-02-25 ES ES00905344T patent/ES2250100T3/es not_active Expired - Lifetime
- 2000-02-25 TW TW089103388A patent/TWI249533B/zh not_active IP Right Cessation
- 2000-02-25 AT AT00905344T patent/ATE305926T1/de not_active IP Right Cessation
- 2000-02-25 CA CA002364801A patent/CA2364801C/en not_active Expired - Fee Related
- 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 WO PCT/JP2000/001098 patent/WO2000050408A1/ja not_active Ceased
- 2000-02-25 DE DE60022986T patent/DE60022986T2/de not_active Expired - Lifetime
- 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 DK DK00905344T patent/DK1156039T3/da active
- 2000-02-25 KR KR1020017009829A patent/KR100647726B1/ko not_active Expired - Fee Related
- 2000-02-25 EP EP00905344A patent/EP1156039B1/de not_active Expired - Lifetime
- 2000-02-25 US US09/926,040 patent/US6680316B1/en not_active Expired - Fee Related
- 2000-02-25 RU RU2001126063/04A patent/RU2232755C2/ru active
2001
- 2001-08-23 NO NO20014099A patent/NO319832B1/no not_active IP Right Cessation

Also Published As

Publication number	Publication date
WO2000050408A1 (en)	2000-08-31
NZ513578A (en)	2005-04-29
EP1156039A1 (de)	2001-11-21
CA2364801A1 (en)	2000-08-31
EP1156039A4 (de)	2002-04-17
TWI249533B (en)	2006-02-21
ATE305926T1 (de)	2005-10-15
AU764393B2 (en)	2003-08-14
DE60022986T2 (de)	2006-05-11
EP1156039B1 (de)	2005-10-05
JP2000247959A (ja)	2000-09-12
HUP0200088A2 (hu)	2002-11-28
CN1148355C (zh)	2004-05-05
CA2364801C (en)	2009-05-19
DE60022986D1 (de)	2006-02-16
KR100647726B1 (ko)	2006-11-23
ES2250100T3 (es)	2006-04-16
NO20014099D0 (no)	2001-08-23
JP4456765B2 (ja)	2010-04-28
US6680316B1 (en)	2004-01-20
HUP0200088A3 (en)	2002-12-28
NO20014099L (no)	2001-10-23
RU2232755C2 (ru)	2004-07-20
CN1341103A (zh)	2002-03-20
KR20010101979A (ko)	2001-11-15
DK1156039T3 (da)	2006-01-30
AU2692800A (en)	2000-09-14
HK1044534A1 (en)	2002-10-25
HK1044534B (zh)	2004-12-10

Legal Events

Date	Code	Title	Description
2010-09-27	MM1K	Lapsed by not paying the annual fees

Publication	Publication Date	Title
JP4328018B2 (ja)	2009-09-09	新規ピリダジン誘導体及びこれを有効成分とする医薬
CA2267103C (en)	2006-05-30	Pyrazolopyridylpyridazinone derivatives and process for the preparation thereof
NO319832B1 (no)	2005-09-19	Pyridazin-3-on-derivater og medikamenter inneholdende disse samt anvendelse av derivatene.
CA2335104C (en)	2008-03-11	Arylalkanoylpyridazines
NO851862L (no)	1985-11-13	Fremgangsmaate ved fremstilling av nye pyrrolobenzimidazoler
JPH09508924A (ja)	1997-09-09	置換３−アリールイデン−７−アザオキシインドール化合物及びその製造方法
NO871879L (no)	1987-11-09	Fremgangsmaate for fremstilling av nye, terapeutisk aktive heterocykliske forbindelser.
CA1108138A (en)	1981-09-01	Triazine derivatives
US7563904B2 (en)	2009-07-21	Synthesis intermediates useful for preparing zolmitriptan
WO1991009598A1 (en)	1991-07-11	Azaoxindole derivatives
JPWO2000050408A1 (ja)	2002-06-11	ピリダジン−３−オン誘導体及びこれを含有する医薬
NO309936B1 (no)	2001-04-23	2,7-Substituerte oktahydro-pyrrol[1,2-a]pyrazin-derivater, anvendelse derav, farmasøytisk preparat, samt mellomprodukter for fremstilling av derivatene
AU618898B2 (en)	1992-01-09	Process for the preparation of oxophthalazinyl acetic acids and analogs thereof
JP2002528549A (ja)	2002-09-03	ホスホジエステラーゼ４阻害剤としての三環性フタラジン誘導体
JP3712619B2 (ja)	2005-11-02	カテコールヒドラゾン誘導体、製造方法及びこれを含む医薬組成物
KR20050039749A (ko)	2005-04-29	리자트립탄의 제조방법
DE68906617T2 (de)	1993-09-23	Substituierte 5,6,7,8-tetrahydroimidazo(1,5-a)pyridine und verfahren zu ihrer herstellung.
JP3999861B2 (ja)	2007-10-31	新規ピリダジン誘導体及びこれを有効成分とする医薬
JPS6136284A (ja)	1986-02-20	チアゾリジン誘導体およびその製造方法
WO1999030711A1 (en)	1999-06-24	Drugs augmenting nkt cells
AU613259B2 (en)	1991-07-25	3-(1,2,5,6-tetrahydropyridyl)-pyrrolopyridines
JPS6228148B2 (de)	1987-06-18
KR20030046086A (ko)	2003-06-12	신규한 카테콜 피라졸 유도체, 그 제조방법 및 이를포함하는 약제학적 조성물
JPH07179467A (ja)	1995-07-18	オキサゼピノピリドインドール誘導体及びその製造方法
NO300540B1 (no)	1997-06-16	Fremgangsmåte til fremstilling av 2-karboksy-3-£2-(dimetylamino)-etyl\|-N-metyl-1H-indol-5-metansulfonamid og lavere alkylestere derav og mellomprodukt i fremstillingen