NO315423B1 - Arylpyridazinoner som biosynteseinhibitorer av prostaglandin endoperoksidase H-syntase, deres fremstilling og farmasöytisk sammensetningomfattende det samme - Google Patents
Arylpyridazinoner som biosynteseinhibitorer av prostaglandin endoperoksidase H-syntase, deres fremstilling og farmasöytisk sammensetningomfattende det samme Download PDFInfo
- Publication number
- NO315423B1 NO315423B1 NO20000863A NO20000863A NO315423B1 NO 315423 B1 NO315423 B1 NO 315423B1 NO 20000863 A NO20000863 A NO 20000863A NO 20000863 A NO20000863 A NO 20000863A NO 315423 B1 NO315423 B1 NO 315423B1
- Authority
- NO
- Norway
- Prior art keywords
- phenyl
- alkyl
- pyridazinone
- fluorophenyl
- hydroxy
- Prior art date
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- 238000002360 preparation method Methods 0.000 title claims description 16
- 150000003180 prostaglandins Chemical class 0.000 title claims description 14
- 230000015572 biosynthetic process Effects 0.000 title claims description 10
- 239000008194 pharmaceutical composition Substances 0.000 title claims description 5
- 239000003112 inhibitor Substances 0.000 title description 4
- 238000000034 method Methods 0.000 claims description 463
- 150000001875 compounds Chemical class 0.000 claims description 424
- -1 di-C1-C6-alkylamino Chemical group 0.000 claims description 274
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 244
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 57
- 229910052739 hydrogen Inorganic materials 0.000 claims description 53
- 239000001257 hydrogen Substances 0.000 claims description 53
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 49
- 150000002367 halogens Chemical class 0.000 claims description 48
- 229910052736 halogen Inorganic materials 0.000 claims description 47
- 150000003839 salts Chemical class 0.000 claims description 42
- 150000002148 esters Chemical class 0.000 claims description 40
- 125000000623 heterocyclic group Chemical group 0.000 claims description 29
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 26
- 125000000217 alkyl group Chemical group 0.000 claims description 14
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 13
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 13
- 125000004739 (C1-C6) alkylsulfonyl group Chemical group 0.000 claims description 11
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 claims description 11
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 10
- 125000002541 furyl group Chemical group 0.000 claims description 10
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 10
- 125000004076 pyridyl group Chemical group 0.000 claims description 10
- 125000001544 thienyl group Chemical group 0.000 claims description 10
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 9
- 239000002168 alkylating agent Substances 0.000 claims description 9
- 229940100198 alkylating agent Drugs 0.000 claims description 9
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 claims description 8
- JCXJVPUVTGWSNB-UHFFFAOYSA-N Nitrogen dioxide Chemical compound O=[N]=O JCXJVPUVTGWSNB-UHFFFAOYSA-N 0.000 claims description 8
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 8
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 claims description 8
- 229910052731 fluorine Inorganic materials 0.000 claims description 8
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 8
- 125000005493 quinolyl group Chemical group 0.000 claims description 8
- 125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 8
- 125000000335 thiazolyl group Chemical group 0.000 claims description 8
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 7
- 125000004844 (C1-C6) alkoxyimino group Chemical group 0.000 claims description 7
- 206010061218 Inflammation Diseases 0.000 claims description 7
- 125000003342 alkenyl group Chemical group 0.000 claims description 7
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 7
- 239000011737 fluorine Substances 0.000 claims description 7
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 7
- 230000004054 inflammatory process Effects 0.000 claims description 7
- 239000000651 prodrug Substances 0.000 claims description 7
- 229940002612 prodrug Drugs 0.000 claims description 7
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 6
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 6
- 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 claims description 5
- 125000004648 C2-C8 alkenyl group Chemical group 0.000 claims description 5
- 125000004649 C2-C8 alkynyl group Chemical group 0.000 claims description 5
- 125000005076 adamantyloxycarbonyl group Chemical group C12(CC3CC(CC(C1)C3)C2)OC(=O)* 0.000 claims description 5
- 239000003814 drug Substances 0.000 claims description 5
- 150000002431 hydrogen Chemical class 0.000 claims description 5
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 5
- 125000006700 (C1-C6) alkylthio group Chemical group 0.000 claims description 4
- 208000002193 Pain Diseases 0.000 claims description 4
- 206010037660 Pyrexia Diseases 0.000 claims description 4
- 125000005073 adamantyl group Chemical group C12(CC3CC(CC(C1)C3)C2)* 0.000 claims description 4
- 125000004639 dihydroindenyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 claims description 4
- 125000005844 heterocyclyloxy group Chemical group 0.000 claims description 4
- 201000008482 osteoarthritis Diseases 0.000 claims description 4
- 125000004368 propenyl group Chemical group C(=CC)* 0.000 claims description 4
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 4
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 claims description 3
- 239000002841 Lewis acid Substances 0.000 claims description 3
- 239000003795 chemical substances by application Substances 0.000 claims description 3
- 150000007517 lewis acids Chemical class 0.000 claims description 3
- QPTNEZSIWLUDPF-UHFFFAOYSA-N 2-(3,4-difluorophenyl)-4-(2-hydroxy-2-methylpropoxy)-5-(4-methylsulfonylphenyl)pyridazin-3-one Chemical compound O=C1C(OCC(C)(O)C)=C(C=2C=CC(=CC=2)S(C)(=O)=O)C=NN1C1=CC=C(F)C(F)=C1 QPTNEZSIWLUDPF-UHFFFAOYSA-N 0.000 claims description 2
- KDJWTTCLGKFONX-CYBMUJFWSA-N 2-(3,4-difluorophenyl)-4-[(2r)-3-hydroxy-2-methylpropoxy]-5-(4-methylsulfonylphenyl)pyridazin-3-one Chemical compound O=C1C(OC[C@@H](CO)C)=C(C=2C=CC(=CC=2)S(C)(=O)=O)C=NN1C1=CC=C(F)C(F)=C1 KDJWTTCLGKFONX-CYBMUJFWSA-N 0.000 claims description 2
- KDJWTTCLGKFONX-ZDUSSCGKSA-N 2-(3,4-difluorophenyl)-4-[(2s)-3-hydroxy-2-methylpropoxy]-5-(4-methylsulfonylphenyl)pyridazin-3-one Chemical compound O=C1C(OC[C@H](CO)C)=C(C=2C=CC(=CC=2)S(C)(=O)=O)C=NN1C1=CC=C(F)C(F)=C1 KDJWTTCLGKFONX-ZDUSSCGKSA-N 0.000 claims description 2
- PORJADFRTDGOOL-UHFFFAOYSA-N 2-(4-fluorophenyl)-4-(3-hydroxy-3-methylbutoxy)-5-(4-methylsulfonylphenyl)pyridazin-3-one Chemical compound O=C1C(OCCC(C)(O)C)=C(C=2C=CC(=CC=2)S(C)(=O)=O)C=NN1C1=CC=C(F)C=C1 PORJADFRTDGOOL-UHFFFAOYSA-N 0.000 claims description 2
- YELGVOXMDKPKTD-UHFFFAOYSA-N 4-[1-(3,4-difluorophenyl)-5-(2-hydroxy-2-methylpropoxy)-6-oxopyridazin-4-yl]benzenesulfonamide Chemical compound O=C1C(OCC(C)(O)C)=C(C=2C=CC(=CC=2)S(N)(=O)=O)C=NN1C1=CC=C(F)C(F)=C1 YELGVOXMDKPKTD-UHFFFAOYSA-N 0.000 claims description 2
- HUHICZNTARYEEM-GFCCVEGCSA-N 4-[1-(3,4-difluorophenyl)-5-[(2r)-3-hydroxy-2-methylpropoxy]-6-oxopyridazin-4-yl]benzenesulfonamide Chemical compound O=C1C(OC[C@@H](CO)C)=C(C=2C=CC(=CC=2)S(N)(=O)=O)C=NN1C1=CC=C(F)C(F)=C1 HUHICZNTARYEEM-GFCCVEGCSA-N 0.000 claims description 2
- HUHICZNTARYEEM-LBPRGKRZSA-N 4-[1-(3,4-difluorophenyl)-5-[(2s)-3-hydroxy-2-methylpropoxy]-6-oxopyridazin-4-yl]benzenesulfonamide Chemical compound O=C1C(OC[C@H](CO)C)=C(C=2C=CC(=CC=2)S(N)(=O)=O)C=NN1C1=CC=C(F)C(F)=C1 HUHICZNTARYEEM-LBPRGKRZSA-N 0.000 claims description 2
- 125000002490 anilino group Chemical group [H]N(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 2
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims description 2
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 2
- 125000004468 heterocyclylthio group Chemical group 0.000 claims description 2
- 125000002883 imidazolyl group Chemical group 0.000 claims description 2
- 125000002757 morpholinyl group Chemical group 0.000 claims description 2
- 125000004043 oxo group Chemical group O=* 0.000 claims description 2
- 125000003356 phenylsulfanyl group Chemical group [*]SC1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 2
- 125000003386 piperidinyl group Chemical group 0.000 claims description 2
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 2
- 125000001425 triazolyl group Chemical group 0.000 claims description 2
- 125000004176 4-fluorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1F)C([H])([H])* 0.000 claims 4
- 125000006507 2,4-difluorobenzyl group Chemical group [H]C1=C(F)C([H])=C(F)C(=C1[H])C([H])([H])* 0.000 claims 3
- 125000004974 2-butenyl group Chemical group C(C=CC)* 0.000 claims 3
- 125000001494 2-propynyl group Chemical group [H]C#CC([H])([H])* 0.000 claims 3
- 206010028980 Neoplasm Diseases 0.000 claims 3
- 201000011510 cancer Diseases 0.000 claims 3
- 239000003937 drug carrier Substances 0.000 claims 3
- 230000002401 inhibitory effect Effects 0.000 claims 3
- XAKBSHICSHRJCL-UHFFFAOYSA-N [CH2]C(=O)C1=CC=CC=C1 Chemical group [CH2]C(=O)C1=CC=CC=C1 XAKBSHICSHRJCL-UHFFFAOYSA-N 0.000 claims 2
- 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 claims 2
- 230000000269 nucleophilic effect Effects 0.000 claims 2
- 125000006479 2-pyridyl methyl group Chemical group [H]C1=C([H])C([H])=C([H])C(=N1)C([H])([H])* 0.000 claims 1
- 125000006494 2-trifluoromethyl benzyl group Chemical group [H]C1=C([H])C([H])=C(C(=C1[H])C([H])([H])*)C(F)(F)F 0.000 claims 1
- 125000004650 C1-C8 alkynyl group Chemical group 0.000 claims 1
- DGYIJVNZSDYBOE-UHFFFAOYSA-N [CH2]C1=CC=NC=C1 Chemical group [CH2]C1=CC=NC=C1 DGYIJVNZSDYBOE-UHFFFAOYSA-N 0.000 claims 1
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 511
- 238000005481 NMR spectroscopy Methods 0.000 description 423
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 198
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 191
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- 229910000069 nitrogen hydride Inorganic materials 0.000 description 142
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 123
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 116
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- 239000013067 intermediate product Substances 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- SUMDYPCJJOFFON-UHFFFAOYSA-N isethionic acid Chemical compound OCCS(O)(=O)=O SUMDYPCJJOFFON-UHFFFAOYSA-N 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 125000005928 isopropyloxycarbonyl group Chemical group [H]C([H])([H])C([H])(OC(*)=O)C([H])([H])[H] 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 230000003907 kidney function Effects 0.000 description 1
- CFHGBZLNZZVTAY-UHFFFAOYSA-N lawesson's reagent Chemical compound C1=CC(OC)=CC=C1P1(=S)SP(=S)(C=2C=CC(OC)=CC=2)S1 CFHGBZLNZZVTAY-UHFFFAOYSA-N 0.000 description 1
- AFRJJFRNGGLMDW-UHFFFAOYSA-N lithium amide Chemical compound [Li+].[NH2-] AFRJJFRNGGLMDW-UHFFFAOYSA-N 0.000 description 1
- 229940040692 lithium hydroxide monohydrate Drugs 0.000 description 1
- GLXDVVHUTZTUQK-UHFFFAOYSA-M lithium hydroxide monohydrate Substances [Li+].O.[OH-] GLXDVVHUTZTUQK-UHFFFAOYSA-M 0.000 description 1
- OTCKOJUMXQWKQG-UHFFFAOYSA-L magnesium bromide Chemical compound [Mg+2].[Br-].[Br-] OTCKOJUMXQWKQG-UHFFFAOYSA-L 0.000 description 1
- WQFXFJBXDHKAKY-UHFFFAOYSA-L magnesium ethynylbenzene dibromide Chemical compound [Mg+2].[Br-].[Br-].C#CC1=CC=CC=C1 WQFXFJBXDHKAKY-UHFFFAOYSA-L 0.000 description 1
- YSMZEMQBSONIMJ-UHFFFAOYSA-M magnesium;2-methanidylpropane;chloride Chemical compound [Mg+2].[Cl-].CC(C)[CH2-] YSMZEMQBSONIMJ-UHFFFAOYSA-M 0.000 description 1
- UKZCGMDMXDLAGZ-UHFFFAOYSA-M magnesium;2-methylpropane;bromide Chemical compound [Mg+2].[Br-].C[C-](C)C UKZCGMDMXDLAGZ-UHFFFAOYSA-M 0.000 description 1
- HTJPDOPKPWUNBX-UHFFFAOYSA-M magnesium;2h-thiophen-2-ide;bromide Chemical compound [Mg+2].[Br-].C=1C=[C-]SC=1 HTJPDOPKPWUNBX-UHFFFAOYSA-M 0.000 description 1
- FGYXQBPXHQHYNU-UHFFFAOYSA-M magnesium;but-2-ene;bromide Chemical compound [Mg+2].[Br-].CC=[C-]C FGYXQBPXHQHYNU-UHFFFAOYSA-M 0.000 description 1
- NXPHGHWWQRMDIA-UHFFFAOYSA-M magnesium;carbanide;bromide Chemical compound [CH3-].[Mg+2].[Br-] NXPHGHWWQRMDIA-UHFFFAOYSA-M 0.000 description 1
- RMGJCSHZTFKPNO-UHFFFAOYSA-M magnesium;ethene;bromide Chemical compound [Mg+2].[Br-].[CH-]=C RMGJCSHZTFKPNO-UHFFFAOYSA-M 0.000 description 1
- OUTILEHLSPAZIN-UHFFFAOYSA-M magnesium;ethylbenzene;chloride Chemical compound [Mg+2].[Cl-].[CH2-]CC1=CC=CC=C1 OUTILEHLSPAZIN-UHFFFAOYSA-M 0.000 description 1
- JGPDOURHDDKDEZ-UHFFFAOYSA-M magnesium;ethynylbenzene;bromide Chemical compound [Mg+2].[Br-].[C-]#CC1=CC=CC=C1 JGPDOURHDDKDEZ-UHFFFAOYSA-M 0.000 description 1
- UFQSTBGEWZUCBQ-UHFFFAOYSA-M magnesium;methanidylcyclohexane;bromide Chemical compound [Mg+2].[Br-].[CH2-]C1CCCCC1 UFQSTBGEWZUCBQ-UHFFFAOYSA-M 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 238000001819 mass spectrum Methods 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Natural products C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 1
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 1
- 229940087646 methanolamine Drugs 0.000 description 1
- HRDXJKGNWSUIBT-UHFFFAOYSA-N methoxybenzene Chemical group [CH2]OC1=CC=CC=C1 HRDXJKGNWSUIBT-UHFFFAOYSA-N 0.000 description 1
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 1
- UAYHHHPYBZQOMJ-UHFFFAOYSA-N methyl 2-(4-fluorophenyl)-3-(4-methylsulfanylphenyl)-4-oxobutanoate Chemical compound C=1C=C(F)C=CC=1C(C(=O)OC)C(C=O)C1=CC=C(SC)C=C1 UAYHHHPYBZQOMJ-UHFFFAOYSA-N 0.000 description 1
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- NLWBJPPMPLPZIE-UHFFFAOYSA-N methyl 4-(bromomethyl)benzoate Chemical compound COC(=O)C1=CC=C(CBr)C=C1 NLWBJPPMPLPZIE-UHFFFAOYSA-N 0.000 description 1
- OJLOPKGSLYJEMD-URPKTTJQSA-N methyl 7-[(1r,2r,3r)-3-hydroxy-2-[(1e)-4-hydroxy-4-methyloct-1-en-1-yl]-5-oxocyclopentyl]heptanoate Chemical compound CCCCC(C)(O)C\C=C\[C@H]1[C@H](O)CC(=O)[C@@H]1CCCCCCC(=O)OC OJLOPKGSLYJEMD-URPKTTJQSA-N 0.000 description 1
- LSEFCHWGJNHZNT-UHFFFAOYSA-M methyl(triphenyl)phosphanium;bromide Chemical compound [Br-].C=1C=CC=CC=1[P+](C=1C=CC=CC=1)(C)C1=CC=CC=C1 LSEFCHWGJNHZNT-UHFFFAOYSA-M 0.000 description 1
- 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 description 1
- 239000002480 mineral oil Substances 0.000 description 1
- 235000010446 mineral oil Nutrition 0.000 description 1
- 229960005249 misoprostol Drugs 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
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- 239000002808 molecular sieve Substances 0.000 description 1
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 description 1
- ZAKLKBFCSHJIRI-UHFFFAOYSA-N mucochloric acid Natural products OC1OC(=O)C(Cl)=C1Cl ZAKLKBFCSHJIRI-UHFFFAOYSA-N 0.000 description 1
- 125000001421 myristyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- PSHKMPUSSFXUIA-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine Chemical compound CN(C)C1=CC=CC=N1 PSHKMPUSSFXUIA-UHFFFAOYSA-N 0.000 description 1
- FOMHZUSUQSYFLM-UHFFFAOYSA-N n-(2,4-dimethoxyphenyl)-2-[3-oxo-6-(trifluoromethyl)-4h-1,4-benzothiazin-2-yl]acetamide Chemical compound COC1=CC(OC)=CC=C1NC(=O)CC1C(=O)NC2=CC(C(F)(F)F)=CC=C2S1 FOMHZUSUQSYFLM-UHFFFAOYSA-N 0.000 description 1
- FMASTMURQSHELY-UHFFFAOYSA-N n-(4-fluoro-2-methylphenyl)-3-methyl-n-[(2-methyl-1h-indol-4-yl)methyl]pyridine-4-carboxamide Chemical compound C1=CC=C2NC(C)=CC2=C1CN(C=1C(=CC(F)=CC=1)C)C(=O)C1=CC=NC=C1C FMASTMURQSHELY-UHFFFAOYSA-N 0.000 description 1
- AYEQJLOHMLYKAV-UHFFFAOYSA-N n-(4-sulfanylphenyl)acetamide Chemical compound CC(=O)NC1=CC=C(S)C=C1 AYEQJLOHMLYKAV-UHFFFAOYSA-N 0.000 description 1
- QROYZARICDCRJK-UHFFFAOYSA-N n-[4-[5-(4-methylsulfonylphenyl)-3-oxo-2-(2,2,2-trifluoroethyl)pyridazin-4-yl]sulfanylphenyl]acetamide Chemical compound C1=CC(NC(=O)C)=CC=C1SC1=C(C=2C=CC(=CC=2)S(C)(=O)=O)C=NN(CC(F)(F)F)C1=O QROYZARICDCRJK-UHFFFAOYSA-N 0.000 description 1
- VFBILHPIHUPBPZ-UHFFFAOYSA-N n-[[2-[4-(difluoromethoxy)-3-propan-2-yloxyphenyl]-1,3-oxazol-4-yl]methyl]-2-ethoxybenzamide Chemical compound CCOC1=CC=CC=C1C(=O)NCC1=COC(C=2C=C(OC(C)C)C(OC(F)F)=CC=2)=N1 VFBILHPIHUPBPZ-UHFFFAOYSA-N 0.000 description 1
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- NNKPHNTWNILINE-UHFFFAOYSA-N n-cyclopropyl-3-fluoro-4-methyl-5-[3-[[1-[2-[2-(methylamino)ethoxy]phenyl]cyclopropyl]amino]-2-oxopyrazin-1-yl]benzamide Chemical compound CNCCOC1=CC=CC=C1C1(NC=2C(N(C=3C(=C(F)C=C(C=3)C(=O)NC3CC3)C)C=CN=2)=O)CC1 NNKPHNTWNILINE-UHFFFAOYSA-N 0.000 description 1
- 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
- RIWRFSMVIUAEBX-UHFFFAOYSA-N n-methyl-1-phenylmethanamine Chemical compound CNCC1=CC=CC=C1 RIWRFSMVIUAEBX-UHFFFAOYSA-N 0.000 description 1
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- KVBGVZZKJNLNJU-UHFFFAOYSA-M naphthalene-2-sulfonate Chemical compound C1=CC=CC2=CC(S(=O)(=O)[O-])=CC=C21 KVBGVZZKJNLNJU-UHFFFAOYSA-M 0.000 description 1
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- CMWTZPSULFXXJA-VIFPVBQESA-N naproxen Chemical compound C1=C([C@H](C)C(O)=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-VIFPVBQESA-N 0.000 description 1
- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
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- JRKICGRDRMAZLK-UHFFFAOYSA-L peroxydisulfate Chemical compound [O-]S(=O)(=O)OOS([O-])(=O)=O JRKICGRDRMAZLK-UHFFFAOYSA-L 0.000 description 1
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- 125000006678 phenoxycarbonyl group Chemical group 0.000 description 1
- 125000001557 phthalyl group Chemical group C(=O)(O)C1=C(C(=O)*)C=CC=C1 0.000 description 1
- 230000035479 physiological effects, processes and functions Effects 0.000 description 1
- 229940075930 picrate Drugs 0.000 description 1
- OXNIZHLAWKMVMX-UHFFFAOYSA-M picrate anion Chemical compound [O-]C1=C([N+]([O-])=O)C=C([N+]([O-])=O)C=C1[N+]([O-])=O OXNIZHLAWKMVMX-UHFFFAOYSA-M 0.000 description 1
- 229950010765 pivalate Drugs 0.000 description 1
- IUGYQRQAERSCNH-UHFFFAOYSA-N pivalic acid Chemical compound CC(C)(C)C(O)=O IUGYQRQAERSCNH-UHFFFAOYSA-N 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 239000011148 porous material Substances 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 235000015320 potassium carbonate Nutrition 0.000 description 1
- NTTOTNSKUYCDAV-UHFFFAOYSA-N potassium hydride Chemical compound [KH] NTTOTNSKUYCDAV-UHFFFAOYSA-N 0.000 description 1
- 229910000105 potassium hydride Inorganic materials 0.000 description 1
- CUNPJFGIODEJLQ-UHFFFAOYSA-M potassium;2,2,2-trifluoroacetate Chemical compound [K+].[O-]C(=O)C(F)(F)F CUNPJFGIODEJLQ-UHFFFAOYSA-M 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 150000003141 primary amines Chemical class 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- VVWRJUBEIPHGQF-UHFFFAOYSA-N propan-2-yl n-propan-2-yloxycarbonyliminocarbamate Chemical compound CC(C)OC(=O)N=NC(=O)OC(C)C VVWRJUBEIPHGQF-UHFFFAOYSA-N 0.000 description 1
- YORCIIVHUBAYBQ-UHFFFAOYSA-N propargyl bromide Chemical compound BrCC#C YORCIIVHUBAYBQ-UHFFFAOYSA-N 0.000 description 1
- 125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 1
- 125000006308 propyl amino group Chemical group 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000002089 prostaglandin antagonist Substances 0.000 description 1
- 239000002599 prostaglandin synthase inhibitor Substances 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- WHMDPDGBKYUEMW-UHFFFAOYSA-N pyridine-2-thiol Chemical compound SC1=CC=CC=N1 WHMDPDGBKYUEMW-UHFFFAOYSA-N 0.000 description 1
- 125000001453 quaternary ammonium group Chemical group 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000004007 reversed phase HPLC Methods 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 239000000523 sample Substances 0.000 description 1
- 229930195734 saturated hydrocarbon Natural products 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 125000003548 sec-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 150000003335 secondary amines Chemical class 0.000 description 1
- XIIOFHFUYBLOLW-UHFFFAOYSA-N selpercatinib Chemical compound OC(COC=1C=C(C=2N(C=1)N=CC=2C#N)C=1C=NC(=CC=1)N1CC2N(C(C1)C2)CC=1C=NC(=CC=1)OC)(C)C XIIOFHFUYBLOLW-UHFFFAOYSA-N 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
- LKZMBDSASOBTPN-UHFFFAOYSA-L silver carbonate Substances [Ag].[O-]C([O-])=O LKZMBDSASOBTPN-UHFFFAOYSA-L 0.000 description 1
- 229910001958 silver carbonate Inorganic materials 0.000 description 1
- 229910001923 silver oxide Inorganic materials 0.000 description 1
- 125000003808 silyl group Chemical group [H][Si]([H])([H])[*] 0.000 description 1
- XGVXKJKTISMIOW-ZDUSSCGKSA-N simurosertib Chemical compound N1N=CC(C=2SC=3C(=O)NC(=NC=3C=2)[C@H]2N3CCC(CC3)C2)=C1C XGVXKJKTISMIOW-ZDUSSCGKSA-N 0.000 description 1
- AWUCVROLDVIAJX-GSVOUGTGSA-N sn-glycerol 3-phosphate Chemical compound OC[C@@H](O)COP(O)(O)=O AWUCVROLDVIAJX-GSVOUGTGSA-N 0.000 description 1
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- GRONZTPUWOOUFQ-UHFFFAOYSA-M sodium;methanol;hydroxide Chemical compound [OH-].[Na+].OC GRONZTPUWOOUFQ-UHFFFAOYSA-M 0.000 description 1
- 239000012258 stirred mixture Substances 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 230000004206 stomach function Effects 0.000 description 1
- 125000000547 substituted alkyl group Chemical group 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- NVBFHJWHLNUMCV-UHFFFAOYSA-N sulfamide Chemical compound NS(N)(=O)=O NVBFHJWHLNUMCV-UHFFFAOYSA-N 0.000 description 1
- 125000000446 sulfanediyl group Chemical group *S* 0.000 description 1
- HXJUTPCZVOIRIF-UHFFFAOYSA-N sulfolane Chemical compound O=S1(=O)CCCC1 HXJUTPCZVOIRIF-UHFFFAOYSA-N 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid Substances OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- QKSQWQOAUQFORH-UHFFFAOYSA-N tert-butyl n-[(2-methylpropan-2-yl)oxycarbonylimino]carbamate Chemical compound CC(C)(C)OC(=O)N=NC(=O)OC(C)(C)C QKSQWQOAUQFORH-UHFFFAOYSA-N 0.000 description 1
- DDPWVABNMBRBFI-UHFFFAOYSA-N tert-butylhydrazine;hydron;chloride Chemical compound Cl.CC(C)(C)NN DDPWVABNMBRBFI-UHFFFAOYSA-N 0.000 description 1
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- CBXCPBUEXACCNR-UHFFFAOYSA-N tetraethylammonium Chemical compound CC[N+](CC)(CC)CC CBXCPBUEXACCNR-UHFFFAOYSA-N 0.000 description 1
- QEMXHQIAXOOASZ-UHFFFAOYSA-N tetramethylammonium Chemical compound C[N+](C)(C)C QEMXHQIAXOOASZ-UHFFFAOYSA-N 0.000 description 1
- 150000003555 thioacetals Chemical class 0.000 description 1
- 125000003396 thiol group Chemical group [H]S* 0.000 description 1
- 150000003573 thiols Chemical class 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 125000004665 trialkylsilyl group Chemical group 0.000 description 1
- 125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 description 1
- WRECIMRULFAWHA-UHFFFAOYSA-N trimethyl borate Chemical compound COB(OC)OC WRECIMRULFAWHA-UHFFFAOYSA-N 0.000 description 1
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 238000001665 trituration Methods 0.000 description 1
- 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 231100000397 ulcer Toxicity 0.000 description 1
- ZDPHROOEEOARMN-UHFFFAOYSA-N undecanoic acid Chemical compound CCCCCCCCCCC(O)=O ZDPHROOEEOARMN-UHFFFAOYSA-N 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
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
- C07D401/06—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 carbon chain containing only aliphatic carbon 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
-
- 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
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- C—CHEMISTRY; METALLURGY
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- 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
- C07D237/18—Sulfur atoms
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- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
- C07D333/26—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom 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
- C07D333/28—Halogen atoms
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- C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
- C07D333/26—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom 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
- C07D333/30—Hetero atoms other than halogen
- C07D333/34—Sulfur atoms
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- 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
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- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
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- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
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- C—CHEMISTRY; METALLURGY
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- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/06—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
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- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
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- C—CHEMISTRY; METALLURGY
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- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
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- Chemical & Material Sciences (AREA)
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- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
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US91702397A | 1997-08-22 | 1997-08-22 | |
US12957098A | 1998-08-05 | 1998-08-05 | |
PCT/US1998/016479 WO1999010331A1 (en) | 1997-08-22 | 1998-08-10 | Arylpyridazinones as prostaglandin endoperoxide h synthase biosynthesis inhibitors |
Publications (3)
Publication Number | Publication Date |
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NO20000863L NO20000863L (no) | 2000-02-22 |
NO20000863D0 NO20000863D0 (no) | 2000-02-22 |
NO315423B1 true NO315423B1 (no) | 2003-09-01 |
Family
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Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
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NO20000863A NO315423B1 (no) | 1997-08-22 | 2000-02-22 | Arylpyridazinoner som biosynteseinhibitorer av prostaglandin endoperoksidase H-syntase, deres fremstilling og farmasöytisk sammensetningomfattende det samme |
Country Status (14)
Country | Link |
---|---|
JP (1) | JP2003516925A (cs) |
KR (1) | KR100675028B1 (cs) |
CN (1) | CN1167687C (cs) |
AR (1) | AR015422A1 (cs) |
AU (1) | AU741317B2 (cs) |
BG (1) | BG64675B1 (cs) |
CZ (1) | CZ300847B6 (cs) |
HU (1) | HUP0400909A3 (cs) |
IL (1) | IL133552A (cs) |
NO (1) | NO315423B1 (cs) |
NZ (1) | NZ501808A (cs) |
PL (1) | PL194175B1 (cs) |
SK (1) | SK286972B6 (cs) |
TR (1) | TR200000478T2 (cs) |
Families Citing this family (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
SK286806B6 (sk) * | 1998-10-27 | 2009-05-07 | Abbott Laboratories | Pyridazinónové zlúčeniny ako inhibítory cyklooxygenázy, farmaceutická kompozícia s ich obsahom a ich použitie |
FR2969606B1 (fr) * | 2010-12-22 | 2013-01-11 | Pf Medicament | Derives de diarylpyridazinones, leur preparation et leur application en therapeutique humaine |
CN107334767B (zh) * | 2017-06-08 | 2019-03-05 | 中国医学科学院医药生物技术研究所 | 一种哒嗪酮类化合物在肿瘤治疗中的应用 |
JP7147444B2 (ja) * | 2018-10-03 | 2022-10-05 | 株式会社島津製作所 | 試料注入装置および試料注入システム |
CN114560814B (zh) * | 2022-03-02 | 2023-10-20 | 天津理工大学 | 一种取代2,3-二氮杂萘酮类化合物的合成方法 |
Family Cites Families (8)
Publication number | Priority date | Publication date | Assignee | Title |
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US4238490A (en) * | 1979-02-12 | 1980-12-09 | Diamond Shamrock Corporation | Antihypertensive pyridazin(2H)-3-ones |
JPS57501328A (cs) * | 1980-08-07 | 1982-07-29 | ||
US4404203A (en) * | 1981-05-14 | 1983-09-13 | Warner-Lambert Company | Substituted 6-phenyl-3(2H)-pyridazinones useful as cardiotonic agents |
WO1988009675A1 (en) * | 1987-06-05 | 1988-12-15 | Medicis Corporation | Inhibition of arachidonic acid metabolism |
AU691673B2 (en) * | 1994-11-14 | 1998-05-21 | Dow Agrosciences Llc | Pyridazinones and their use as fungicides |
US5622948A (en) * | 1994-12-01 | 1997-04-22 | Syntex (U.S.A.) Inc. | Pyrrole pyridazine and pyridazinone anti-inflammatory agents |
WO1996041645A1 (en) * | 1995-06-12 | 1996-12-27 | G.D. Searle & Co. | Combination of a cyclooxygenase-2 inhibitor and a leukotriene b4 receptor antagonist for the treatment of inflammations |
EP0975604B1 (en) * | 1997-03-14 | 2004-07-21 | Merck Frosst Canada & Co. | Pyridazinones as inhibitors of cyclooxygenase-2 |
-
1998
- 1998-08-10 HU HU0400909A patent/HUP0400909A3/hu unknown
- 1998-08-10 CZ CZ20000446A patent/CZ300847B6/cs not_active IP Right Cessation
- 1998-08-10 SK SK231-2000A patent/SK286972B6/sk not_active IP Right Cessation
- 1998-08-10 TR TR2000/00478T patent/TR200000478T2/xx unknown
- 1998-08-10 AU AU86976/98A patent/AU741317B2/en not_active Ceased
- 1998-08-10 KR KR1020007001824A patent/KR100675028B1/ko not_active Expired - Fee Related
- 1998-08-10 CN CNB988083221A patent/CN1167687C/zh not_active Expired - Fee Related
- 1998-08-10 JP JP2000507660A patent/JP2003516925A/ja active Pending
- 1998-08-10 PL PL98355418A patent/PL194175B1/pl not_active IP Right Cessation
- 1998-08-10 NZ NZ501808A patent/NZ501808A/xx unknown
- 1998-08-10 IL IL13355298A patent/IL133552A/xx not_active IP Right Cessation
- 1998-08-24 AR ARP980104193A patent/AR015422A1/es active IP Right Grant
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2000
- 2000-02-22 NO NO20000863A patent/NO315423B1/no not_active IP Right Cessation
- 2000-03-15 BG BG104241A patent/BG64675B1/bg unknown
Also Published As
Publication number | Publication date |
---|---|
TR200000478T2 (tr) | 2002-04-22 |
HUP0400909A3 (en) | 2004-10-28 |
CN1167687C (zh) | 2004-09-22 |
SK2312000A3 (en) | 2001-02-12 |
JP2003516925A (ja) | 2003-05-20 |
PL194175B1 (pl) | 2007-05-31 |
CN1277605A (zh) | 2000-12-20 |
HUP0400909A2 (hu) | 2004-07-28 |
SK286972B6 (sk) | 2009-08-06 |
NZ501808A (en) | 2002-12-20 |
NO20000863L (no) | 2000-02-22 |
CZ2000446A3 (cs) | 2000-05-17 |
BG104241A (en) | 2000-10-31 |
CZ300847B6 (cs) | 2009-08-26 |
AU8697698A (en) | 1999-03-16 |
KR20010023196A (ko) | 2001-03-26 |
IL133552A0 (en) | 2001-04-30 |
NO20000863D0 (no) | 2000-02-22 |
KR100675028B1 (ko) | 2007-01-29 |
PL355418A1 (en) | 2004-04-19 |
AR015422A1 (es) | 2001-05-02 |
IL133552A (en) | 2005-12-18 |
AU741317B2 (en) | 2001-11-29 |
BG64675B1 (bg) | 2005-11-30 |
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