NO314629B1 - 5-lipoksygenase-inhibitorer - Google Patents
5-lipoksygenase-inhibitorer Download PDFInfo
- Publication number
- NO314629B1 NO314629B1 NO19971773A NO971773A NO314629B1 NO 314629 B1 NO314629 B1 NO 314629B1 NO 19971773 A NO19971773 A NO 19971773A NO 971773 A NO971773 A NO 971773A NO 314629 B1 NO314629 B1 NO 314629B1
- Authority
- NO
- Norway
- Prior art keywords
- tetrahydro
- pyran
- phenyl
- methylimidazol
- mmol
- Prior art date
Links
- 239000000867 Lipoxygenase Inhibitor Substances 0.000 title description 3
- 150000001875 compounds Chemical class 0.000 claims abstract description 187
- -1 hydroxy, cyano, amino Chemical group 0.000 claims abstract description 35
- 150000003839 salts Chemical class 0.000 claims abstract description 19
- 229910052799 carbon Inorganic materials 0.000 claims abstract description 8
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 8
- 125000005843 halogen group Chemical group 0.000 claims abstract description 7
- 241000124008 Mammalia Species 0.000 claims abstract description 5
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims abstract description 5
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 4
- 125000000843 phenylene group Chemical group C1(=C(C=CC=C1)*)* 0.000 claims abstract description 4
- 125000001424 substituent group Chemical group 0.000 claims abstract description 4
- 125000001376 1,2,4-triazolyl group Chemical group N1N=C(N=C1)* 0.000 claims abstract description 3
- 125000004429 atom Chemical group 0.000 claims abstract description 3
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 3
- 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 3
- 125000002883 imidazolyl group Chemical group 0.000 claims abstract description 3
- 125000004433 nitrogen atom Chemical group N* 0.000 claims abstract description 3
- 125000003226 pyrazolyl group Chemical group 0.000 claims abstract description 3
- 125000000168 pyrrolyl group Chemical group 0.000 claims abstract description 3
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 36
- DFULQBDWIYRMDM-UHFFFAOYSA-N 2-methyl-4-[3-[4-(2-methylimidazol-1-yl)phenyl]sulfanylphenyl]oxane-4-carboxamide Chemical compound C1COC(C)CC1(C(N)=O)C1=CC=CC(SC=2C=CC(=CC=2)N2C(=NC=C2)C)=C1 DFULQBDWIYRMDM-UHFFFAOYSA-N 0.000 claims description 8
- 125000000217 alkyl group Chemical group 0.000 claims description 6
- VPTONMHDLLMOOV-UHFFFAOYSA-N 4-[3-[4-(2-methylimidazol-1-yl)phenyl]sulfanylphenyl]oxane-4-carboxamide Chemical compound CC1=NC=CN1C(C=C1)=CC=C1SC1=CC=CC(C2(CCOCC2)C(N)=O)=C1 VPTONMHDLLMOOV-UHFFFAOYSA-N 0.000 claims description 5
- WOTAALFHBLLBGH-UHFFFAOYSA-N 4-[3-fluoro-5-[[4-(2-methylimidazol-1-yl)phenyl]methoxy]phenyl]oxane-4-carboxamide Chemical compound CC1=NC=CN1C(C=C1)=CC=C1COC1=CC(F)=CC(C2(CCOCC2)C(N)=O)=C1 WOTAALFHBLLBGH-UHFFFAOYSA-N 0.000 claims description 5
- 239000000126 substance Substances 0.000 claims description 5
- 125000001153 fluoro group Chemical group F* 0.000 claims description 4
- VIIMIHGRUTXXBD-UHFFFAOYSA-N 4-[3-[4-(pyrrol-1-ylmethyl)phenyl]sulfanylphenyl]oxane-4-carboxamide Chemical compound C=1C=CC(SC=2C=CC(CN3C=CC=C3)=CC=2)=CC=1C1(C(=O)N)CCOCC1 VIIMIHGRUTXXBD-UHFFFAOYSA-N 0.000 claims description 3
- 229910052739 hydrogen Inorganic materials 0.000 claims description 3
- MFDRVJVFAWBQQJ-UHFFFAOYSA-N n-methoxy-1-[4-[3-[4-(2-methylimidazol-1-yl)phenyl]sulfanylphenyl]oxan-4-yl]methanimine Chemical compound C=1C=CC(SC=2C=CC(=CC=2)N2C(=NC=C2)C)=CC=1C1(C=NOC)CCOCC1 MFDRVJVFAWBQQJ-UHFFFAOYSA-N 0.000 claims description 3
- 125000003161 (C1-C6) alkylene group Chemical group 0.000 claims description 2
- 125000001989 1,3-phenylene group Chemical group [H]C1=C([H])C([*:1])=C([H])C([*:2])=C1[H] 0.000 claims description 2
- 125000001140 1,4-phenylene group Chemical group [H]C1=C([H])C([*:2])=C([H])C([H])=C1[*:1] 0.000 claims description 2
- 125000003545 alkoxy group Chemical group 0.000 claims description 2
- 230000000172 allergic effect Effects 0.000 claims description 2
- 208000010668 atopic eczema Diseases 0.000 claims description 2
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- 230000004968 inflammatory condition Effects 0.000 claims description 2
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 claims 1
- 239000005977 Ethylene Substances 0.000 claims 1
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical group O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 claims 1
- 101100295738 Gallus gallus COR3 gene Proteins 0.000 claims 1
- 229910052731 fluorine Inorganic materials 0.000 claims 1
- 239000011737 fluorine Substances 0.000 claims 1
- 235000019256 formaldehyde Nutrition 0.000 claims 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims 1
- 208000027866 inflammatory disease Diseases 0.000 abstract description 5
- 208000024172 Cardiovascular disease Diseases 0.000 abstract description 4
- 125000002947 alkylene group Chemical group 0.000 abstract description 4
- 206010020751 Hypersensitivity Diseases 0.000 abstract description 3
- 239000004480 active ingredient Substances 0.000 abstract description 3
- 230000007815 allergy Effects 0.000 abstract description 3
- 102000001381 Arachidonate 5-Lipoxygenase Human genes 0.000 abstract description 2
- 108010093579 Arachidonate 5-lipoxygenase Proteins 0.000 abstract description 2
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 abstract 4
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 abstract 1
- 125000001399 1,2,3-triazolyl group Chemical group N1N=NC(=C1)* 0.000 abstract 1
- 208000026935 allergic disease Diseases 0.000 abstract 1
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 abstract 1
- 125000005678 ethenylene group Chemical group [H]C([*:1])=C([H])[*:2] 0.000 abstract 1
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 abstract 1
- 125000001041 indolyl group Chemical group 0.000 abstract 1
- 125000005564 oxazolylene group Chemical group 0.000 abstract 1
- 125000005551 pyridylene group Chemical group 0.000 abstract 1
- 125000005557 thiazolylene group Chemical group 0.000 abstract 1
- 125000005556 thienylene group Chemical group 0.000 abstract 1
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 170
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 162
- 238000005481 NMR spectroscopy Methods 0.000 description 120
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 102
- 239000000203 mixture Substances 0.000 description 93
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 86
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 63
- 238000000034 method Methods 0.000 description 60
- 239000000243 solution Substances 0.000 description 57
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 50
- 239000012267 brine Substances 0.000 description 49
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 49
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 48
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 43
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 42
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 34
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 34
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 33
- 239000000284 extract Substances 0.000 description 32
- 239000007787 solid Substances 0.000 description 32
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 30
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 27
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 24
- 235000019341 magnesium sulphate Nutrition 0.000 description 24
- 239000011541 reaction mixture Substances 0.000 description 23
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 21
- 238000004440 column chromatography Methods 0.000 description 21
- 238000002360 preparation method Methods 0.000 description 20
- 238000003756 stirring Methods 0.000 description 20
- 238000006243 chemical reaction Methods 0.000 description 19
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 18
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 17
- 125000003356 phenylsulfanyl group Chemical group [*]SC1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 17
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 15
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 15
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 description 14
- 239000010410 layer Substances 0.000 description 14
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 14
- 238000001704 evaporation Methods 0.000 description 13
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 13
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 13
- 239000003921 oil Substances 0.000 description 13
- 239000000725 suspension Substances 0.000 description 13
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 12
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 12
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 12
- 239000007788 liquid Substances 0.000 description 12
- 238000000746 purification Methods 0.000 description 12
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 12
- 230000008020 evaporation Effects 0.000 description 11
- 239000012044 organic layer Substances 0.000 description 11
- NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 11
- 229920006395 saturated elastomer Polymers 0.000 description 11
- 239000000741 silica gel Substances 0.000 description 11
- 229910002027 silica gel Inorganic materials 0.000 description 11
- 239000002904 solvent Substances 0.000 description 11
- REVPKMONQSPHGF-UHFFFAOYSA-N 1-(4-iodophenyl)-2-methylimidazole Chemical compound CC1=NC=CN1C1=CC=C(I)C=C1 REVPKMONQSPHGF-UHFFFAOYSA-N 0.000 description 10
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 10
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 10
- 239000012312 sodium hydride Substances 0.000 description 10
- 229910000104 sodium hydride Inorganic materials 0.000 description 10
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 9
- 239000002585 base Substances 0.000 description 9
- 239000012043 crude product Substances 0.000 description 9
- 239000012299 nitrogen atmosphere Substances 0.000 description 9
- 239000012074 organic phase Substances 0.000 description 9
- 238000010992 reflux Methods 0.000 description 9
- UGUHPJCDONTQRD-UHFFFAOYSA-N 4-(3-iodophenyl)-2-methyloxane-4-carbonitrile Chemical compound C1COC(C)CC1(C#N)C1=CC=CC(I)=C1 UGUHPJCDONTQRD-UHFFFAOYSA-N 0.000 description 8
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 8
- ZNSMNVMLTJELDZ-UHFFFAOYSA-N Bis(2-chloroethyl)ether Chemical compound ClCCOCCCl ZNSMNVMLTJELDZ-UHFFFAOYSA-N 0.000 description 8
- YZXBAPSDXZZRGB-DOFZRALJSA-N arachidonic acid Chemical compound CCCCC\C=C/C\C=C/C\C=C/C\C=C/CCCC(O)=O YZXBAPSDXZZRGB-DOFZRALJSA-N 0.000 description 8
- 239000006185 dispersion Substances 0.000 description 8
- WHLPQLRCPSXNEZ-UHFFFAOYSA-N ethyl 4-(3-fluoro-5-phenylmethoxyphenyl)oxane-4-carboxylate Chemical compound C=1C(F)=CC(OCC=2C=CC=CC=2)=CC=1C1(C(=O)OCC)CCOCC1 WHLPQLRCPSXNEZ-UHFFFAOYSA-N 0.000 description 8
- 238000001914 filtration Methods 0.000 description 8
- 239000002480 mineral oil Substances 0.000 description 8
- 235000010446 mineral oil Nutrition 0.000 description 8
- CIUMNJWNOIMPHU-UHFFFAOYSA-N 2-methyl-4-[3-[4-(2-methylimidazol-1-yl)phenyl]sulfanylphenyl]oxane-4-carbonitrile Chemical compound C1COC(C)CC1(C#N)C1=CC=CC(SC=2C=CC(=CC=2)N2C(=NC=C2)C)=C1 CIUMNJWNOIMPHU-UHFFFAOYSA-N 0.000 description 7
- GBKXHHZPDLLXCU-UHFFFAOYSA-N 4-[3-fluoro-5-[4-(2-methylimidazol-1-yl)phenyl]sulfanylphenyl]oxane-4-carbonitrile Chemical compound CC1=NC=CN1C(C=C1)=CC=C1SC1=CC(F)=CC(C2(CCOCC2)C#N)=C1 GBKXHHZPDLLXCU-UHFFFAOYSA-N 0.000 description 7
- 239000007864 aqueous solution Substances 0.000 description 7
- 239000012230 colorless oil Substances 0.000 description 7
- 238000007796 conventional method Methods 0.000 description 7
- 238000001816 cooling Methods 0.000 description 7
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 7
- 229910000027 potassium carbonate Inorganic materials 0.000 description 7
- ZWIIPKTYHOPGIG-UHFFFAOYSA-N 1-[4-(chloromethyl)phenyl]-2-methylimidazole;hydrochloride Chemical compound Cl.CC1=NC=CN1C1=CC=C(CCl)C=C1 ZWIIPKTYHOPGIG-UHFFFAOYSA-N 0.000 description 6
- NNKXEAZAONRVJR-UHFFFAOYSA-N 2-methyl-4-[3-tri(propan-2-yl)silylsulfanylphenyl]oxane-4-carbonitrile Chemical compound CC(C)[Si](C(C)C)(C(C)C)SC1=CC=CC(C2(CC(C)OCC2)C#N)=C1 NNKXEAZAONRVJR-UHFFFAOYSA-N 0.000 description 6
- 102000003820 Lipoxygenases Human genes 0.000 description 6
- 108090000128 Lipoxygenases Proteins 0.000 description 6
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
- ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 description 6
- WTOCSHWGOZQZQQ-UHFFFAOYSA-N ethyl 2-(3-fluoro-5-phenylmethoxyphenyl)acetate Chemical compound CCOC(=O)CC1=CC(F)=CC(OCC=2C=CC=CC=2)=C1 WTOCSHWGOZQZQQ-UHFFFAOYSA-N 0.000 description 6
- 239000000047 product Substances 0.000 description 6
- 235000017557 sodium bicarbonate Nutrition 0.000 description 6
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 6
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 6
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 5
- LXKNAUOWEJWGTE-UHFFFAOYSA-N 2-(3-methoxyphenyl)acetonitrile Chemical compound COC1=CC=CC(CC#N)=C1 LXKNAUOWEJWGTE-UHFFFAOYSA-N 0.000 description 5
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 5
- 239000002253 acid Substances 0.000 description 5
- 239000003054 catalyst Substances 0.000 description 5
- WSNKLYIWJLWVDJ-UHFFFAOYSA-N ethyl 4-(3-fluoro-5-hydroxyphenyl)oxane-4-carboxylate Chemical compound C=1C(O)=CC(F)=CC=1C1(C(=O)OCC)CCOCC1 WSNKLYIWJLWVDJ-UHFFFAOYSA-N 0.000 description 5
- SNAQPKWTPCDKQR-UHFFFAOYSA-N ethyl 4-[3-fluoro-5-[[4-(2-methylimidazol-1-yl)phenyl]methoxy]phenyl]oxane-4-carboxylate Chemical compound C=1C(F)=CC(OCC=2C=CC(=CC=2)N2C(=NC=C2)C)=CC=1C1(C(=O)OCC)CCOCC1 SNAQPKWTPCDKQR-UHFFFAOYSA-N 0.000 description 5
- 239000012442 inert solvent Substances 0.000 description 5
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 5
- 239000002244 precipitate Substances 0.000 description 5
- 230000035484 reaction time Effects 0.000 description 5
- 238000001953 recrystallisation Methods 0.000 description 5
- 239000012258 stirred mixture Substances 0.000 description 5
- LXBGSDVWAMZHDD-UHFFFAOYSA-N 2-methyl-1h-imidazole Chemical compound CC1=NC=CN1 LXBGSDVWAMZHDD-UHFFFAOYSA-N 0.000 description 4
- QAXBNRVKZATOSP-UHFFFAOYSA-N 4-(3-hydroxyphenyl)oxane-4-carbonitrile Chemical compound OC1=CC=CC(C2(CCOCC2)C#N)=C1 QAXBNRVKZATOSP-UHFFFAOYSA-N 0.000 description 4
- VQTVCQKDMCRNES-UHFFFAOYSA-N 4-[3-fluoro-5-[[4-(2-methylimidazol-1-yl)phenyl]methoxy]phenyl]oxane-4-carboxylic acid Chemical compound CC1=NC=CN1C(C=C1)=CC=C1COC1=CC(F)=CC(C2(CCOCC2)C(O)=O)=C1 VQTVCQKDMCRNES-UHFFFAOYSA-N 0.000 description 4
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 4
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 4
- 229910004298 SiO 2 Inorganic materials 0.000 description 4
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
- 230000009471 action Effects 0.000 description 4
- 239000008346 aqueous phase Substances 0.000 description 4
- 239000003153 chemical reaction reagent Substances 0.000 description 4
- OAMZXMDZZWGPMH-UHFFFAOYSA-N ethyl acetate;toluene Chemical compound CCOC(C)=O.CC1=CC=CC=C1 OAMZXMDZZWGPMH-UHFFFAOYSA-N 0.000 description 4
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 4
- NROKBHXJSPEDAR-UHFFFAOYSA-M potassium fluoride Chemical compound [F-].[K+] NROKBHXJSPEDAR-UHFFFAOYSA-M 0.000 description 4
- 238000010898 silica gel chromatography Methods 0.000 description 4
- 239000011734 sodium Substances 0.000 description 4
- 235000009518 sodium iodide Nutrition 0.000 description 4
- 229910052938 sodium sulfate Inorganic materials 0.000 description 4
- 235000011152 sodium sulphate Nutrition 0.000 description 4
- MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 description 4
- UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 description 4
- BAPDTHNKTSOIBC-UHFFFAOYSA-N 1-[(4-iodophenyl)methyl]pyrrole Chemical compound C1=CC(I)=CC=C1CN1C=CC=C1 BAPDTHNKTSOIBC-UHFFFAOYSA-N 0.000 description 3
- VFTFKUDGYRBSAL-UHFFFAOYSA-N 15-crown-5 Chemical compound C1COCCOCCOCCOCCO1 VFTFKUDGYRBSAL-UHFFFAOYSA-N 0.000 description 3
- LTMRRSWNXVJMBA-UHFFFAOYSA-L 2,2-diethylpropanedioate Chemical compound CCC(CC)(C([O-])=O)C([O-])=O LTMRRSWNXVJMBA-UHFFFAOYSA-L 0.000 description 3
- LVOKGAHCTHNWIL-UHFFFAOYSA-N 2-(3-iodophenyl)acetonitrile Chemical compound IC1=CC=CC(CC#N)=C1 LVOKGAHCTHNWIL-UHFFFAOYSA-N 0.000 description 3
- JCBLGYQAGGATJS-UHFFFAOYSA-N 4-(3-fluoro-5-phenylmethoxyphenyl)oxane-4-carbaldehyde Chemical compound C=1C(C2(CCOCC2)C=O)=CC(F)=CC=1OCC1=CC=CC=C1 JCBLGYQAGGATJS-UHFFFAOYSA-N 0.000 description 3
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- RYVBINGWVJJDPU-UHFFFAOYSA-M tributyl(hexadecyl)phosphanium;bromide Chemical compound [Br-].CCCCCCCCCCCCCCCC[P+](CCCC)(CCCC)CCCC RYVBINGWVJJDPU-UHFFFAOYSA-M 0.000 description 1
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/12—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/08—Antiallergic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/56—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D309/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings
- C07D309/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
- C07D309/08—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having no 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
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Rheumatology (AREA)
- Cardiology (AREA)
- Pulmonology (AREA)
- Immunology (AREA)
- Pain & Pain Management (AREA)
- Heart & Thoracic Surgery (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Plural Heterocyclic Compounds (AREA)
- Medicines Containing Plant Substances (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP9401747 | 1994-10-18 | ||
| PCT/IB1995/000408 WO1996011911A1 (en) | 1994-10-18 | 1995-05-29 | 5-lipoxygenase inhibitors |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| NO971773D0 NO971773D0 (no) | 1997-04-17 |
| NO971773L NO971773L (no) | 1997-06-17 |
| NO314629B1 true NO314629B1 (no) | 2003-04-22 |
Family
ID=14098722
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO19971773A NO314629B1 (no) | 1994-10-18 | 1997-04-17 | 5-lipoksygenase-inhibitorer |
Country Status (31)
| Country | Link |
|---|---|
| EP (1) | EP0787127B1 (cs) |
| JP (1) | JP3032579B2 (cs) |
| CN (1) | CN1093536C (cs) |
| AT (1) | ATE198474T1 (cs) |
| AU (1) | AU681520B2 (cs) |
| BG (1) | BG61768B1 (cs) |
| CA (1) | CA2202057C (cs) |
| CO (1) | CO4480026A1 (cs) |
| CZ (1) | CZ287350B6 (cs) |
| DE (1) | DE69519804T2 (cs) |
| DK (1) | DK0787127T3 (cs) |
| ES (1) | ES2153033T3 (cs) |
| FI (1) | FI971632A0 (cs) |
| GR (1) | GR3035471T3 (cs) |
| HU (1) | HU221543B (cs) |
| IL (1) | IL115581A (cs) |
| LV (1) | LV11468B (cs) |
| MY (1) | MY114680A (cs) |
| NO (1) | NO314629B1 (cs) |
| NZ (1) | NZ285163A (cs) |
| PE (1) | PE49196A1 (cs) |
| PL (1) | PL180104B1 (cs) |
| RU (1) | RU2136666C1 (cs) |
| SI (1) | SI9500392A (cs) |
| SK (1) | SK281577B6 (cs) |
| TR (1) | TR199501274A2 (cs) |
| TW (1) | TW411339B (cs) |
| UA (1) | UA45312C2 (cs) |
| WO (1) | WO1996011911A1 (cs) |
| YU (1) | YU65995A (cs) |
| ZA (1) | ZA958748B (cs) |
Families Citing this family (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6239285B1 (en) | 1998-02-06 | 2001-05-29 | Pfizer Inc | Process for making 5-lipoxygenase inhibitors having varied heterocyclic ring systems |
| US6194585B1 (en) * | 1998-12-22 | 2001-02-27 | Pfizer Inc. | Process for preparing 5-lipoxygenase inhibitors |
| US6344563B1 (en) | 1999-08-31 | 2002-02-05 | Timothy Norris | Process for making 5-lipoxygenase inhibitors having varied heterocyclic ring systems |
| US6346624B1 (en) * | 1999-08-31 | 2002-02-12 | Pfizer Inc | Process for making 5-lipoxygenase inhibitors having varied heterocyclic ring systems |
| SG87145A1 (en) * | 1999-08-31 | 2002-03-19 | Pfizer Prod Inc | Process for making 5-lipoxygenase inhibitors having varied heterocyclic ring systems |
| CZ303632B6 (cs) * | 2000-03-24 | 2013-01-23 | Euro-Celtique S.A. | Arylem substituované pyrazoly, triazoly a tetrazoly a jejich pouzití |
| EP1383874B1 (en) * | 2001-04-20 | 2009-12-23 | Novozymes A/S | Variants of lipoxygenase and their use |
| GB0302094D0 (en) | 2003-01-29 | 2003-02-26 | Pharmagene Lab Ltd | EP4 receptor antagonists |
| GB0324269D0 (en) | 2003-10-16 | 2003-11-19 | Pharmagene Lab Ltd | EP4 receptor antagonists |
| RS20090211A (sr) * | 2006-11-27 | 2010-10-31 | Pfizer Products Inc. | Analozi pirazola |
| EA201000703A1 (ru) * | 2007-11-26 | 2010-12-30 | Пфайзер Инк. | Производные пиразола в качестве ингибиторов 5-lo |
| MX2014010272A (es) * | 2012-02-28 | 2015-08-14 | Piramal Entpr Ltd | Derivados del acido fenil alcanoico como agonistas gpr. |
| TWI827583B (zh) | 2018-03-08 | 2024-01-01 | 美商英塞特公司 | 作為ＰＩ３Ｋ-γ抑制劑之胺基吡嗪二醇化合物 |
| WO2020010003A1 (en) | 2018-07-02 | 2020-01-09 | Incyte Corporation | AMINOPYRAZINE DERIVATIVES AS PI3K-γ INHIBITORS |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ES2001730A6 (es) * | 1987-01-14 | 1988-06-01 | Ferrer Int | Procedimiento de obtencion del acio 2,3-dihidro-5-(b-(1h-imidazol-1-il) etoxi)-1h-inden-1-carboxilico |
| EP0462830B1 (en) * | 1990-06-21 | 1995-10-18 | Zeneca Limited | Cyclic ether derivatives |
| IE913866A1 (en) * | 1990-11-28 | 1992-06-03 | Ici Plc | Aryl derivatives |
| EP0505122A1 (en) * | 1991-03-21 | 1992-09-23 | Zeneca Limited | Alpha, alpha-dialkylbenzyl derivatives |
| EP0540165A1 (en) * | 1991-10-03 | 1993-05-05 | Zeneca Limited | Alkanoic acid derivatives |
| KR100190728B1 (ko) * | 1993-06-14 | 1999-06-01 | 디. 제이. 우드, 스피겔 알렌 제이 | 이미다졸 리폭시게나제 저해제 |
-
1994
- 1994-10-18 SK SK1287-95A patent/SK281577B6/sk unknown
-
1995
- 1995-05-29 CZ CZ19971177A patent/CZ287350B6/cs not_active IP Right Cessation
- 1995-05-29 PL PL95319727A patent/PL180104B1/pl not_active IP Right Cessation
- 1995-05-29 EP EP95918121A patent/EP0787127B1/en not_active Expired - Lifetime
- 1995-05-29 WO PCT/IB1995/000408 patent/WO1996011911A1/en not_active Ceased
- 1995-05-29 CA CA002202057A patent/CA2202057C/en not_active Expired - Fee Related
- 1995-05-29 NZ NZ285163A patent/NZ285163A/en unknown
- 1995-05-29 DE DE69519804T patent/DE69519804T2/de not_active Expired - Fee Related
- 1995-05-29 HU HU9701853A patent/HU221543B/hu not_active IP Right Cessation
- 1995-05-29 CN CN95195926A patent/CN1093536C/zh not_active Expired - Fee Related
- 1995-05-29 RU RU97106099/04A patent/RU2136666C1/ru not_active IP Right Cessation
- 1995-05-29 JP JP8513058A patent/JP3032579B2/ja not_active Expired - Fee Related
- 1995-05-29 DK DK95918121T patent/DK0787127T3/da active
- 1995-05-29 ES ES95918121T patent/ES2153033T3/es not_active Expired - Lifetime
- 1995-05-29 AU AU24174/95A patent/AU681520B2/en not_active Ceased
- 1995-05-29 AT AT95918121T patent/ATE198474T1/de not_active IP Right Cessation
- 1995-09-12 TW TW084109522A patent/TW411339B/zh not_active IP Right Cessation
- 1995-10-02 CO CO95045652A patent/CO4480026A1/es unknown
- 1995-10-12 IL IL11558195A patent/IL115581A/xx not_active IP Right Cessation
- 1995-10-13 UA UA95104510A patent/UA45312C2/uk unknown
- 1995-10-16 MY MYPI95003103A patent/MY114680A/en unknown
- 1995-10-17 YU YU65995A patent/YU65995A/sh unknown
- 1995-10-17 SI SI9500392A patent/SI9500392A/sl unknown
- 1995-10-17 LV LVP-95-313A patent/LV11468B/en unknown
- 1995-10-17 PE PE1995282113A patent/PE49196A1/es not_active Application Discontinuation
- 1995-10-17 ZA ZA958748A patent/ZA958748B/xx unknown
- 1995-10-18 BG BG100070A patent/BG61768B1/bg unknown
- 1995-10-18 TR TR95/01274A patent/TR199501274A2/xx unknown
-
1997
- 1997-04-17 NO NO19971773A patent/NO314629B1/no unknown
- 1997-04-17 FI FI971632A patent/FI971632A0/fi not_active IP Right Cessation
-
2001
- 2001-02-23 GR GR20010400310T patent/GR3035471T3/el not_active IP Right Cessation
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