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
- SYOBOTSCMVRZPR-UHFFFAOYSA-N 4-(3-methoxyphenyl)oxane-4-carbonitrile Chemical compound COC1=CC=CC(C2(CCOCC2)C#N)=C1 SYOBOTSCMVRZPR-UHFFFAOYSA-N 0.000 description 3
- KWOYURNKYINOFS-UHFFFAOYSA-N 4-[3-[4-(2-methylimidazol-1-yl)phenoxy]phenyl]oxane-4-carbonitrile Chemical compound CC1=NC=CN1C(C=C1)=CC=C1OC1=CC=CC(C2(CCOCC2)C#N)=C1 KWOYURNKYINOFS-UHFFFAOYSA-N 0.000 description 3
- QVCJYNZQZXKOCN-UHFFFAOYSA-N 4-[3-[4-(2-methylimidazol-1-yl)phenyl]sulfanylphenyl]oxane-4-carboxylic acid Chemical compound CC1=NC=CN1C(C=C1)=CC=C1SC1=CC=CC(C2(CCOCC2)C(O)=O)=C1 QVCJYNZQZXKOCN-UHFFFAOYSA-N 0.000 description 3
- WTWLJFHCOHBRHP-UHFFFAOYSA-N 4-[3-[4-(pyrrol-1-ylmethyl)phenyl]sulfanylphenyl]oxane-4-carboxylic acid Chemical compound C=1C=CC(SC=2C=CC(CN3C=CC=C3)=CC=2)=CC=1C1(C(=O)O)CCOCC1 WTWLJFHCOHBRHP-UHFFFAOYSA-N 0.000 description 3
- BRUBVOQNTLFQLR-UHFFFAOYSA-N 4-[3-fluoro-5-[4-(2-methylpyrrol-1-yl)phenyl]sulfanylphenyl]oxane-4-carbonitrile Chemical compound CC1=CC=CN1C(C=C1)=CC=C1SC1=CC(F)=CC(C2(CCOCC2)C#N)=C1 BRUBVOQNTLFQLR-UHFFFAOYSA-N 0.000 description 3
- BXCOSJFERUGDDD-UHFFFAOYSA-N 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(CCOCC2)C#N)=C1 BXCOSJFERUGDDD-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 3
- QPLDLSVMHZLSFG-UHFFFAOYSA-N Copper oxide Chemical compound [Cu]=O QPLDLSVMHZLSFG-UHFFFAOYSA-N 0.000 description 3
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 3
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 3
- 229910052783 alkali metal Inorganic materials 0.000 description 3
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 3
- QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 3
- 235000019270 ammonium chloride Nutrition 0.000 description 3
- 235000011114 ammonium hydroxide Nutrition 0.000 description 3
- 229940114079 arachidonic acid Drugs 0.000 description 3
- 235000021342 arachidonic acid Nutrition 0.000 description 3
- 208000006673 asthma Diseases 0.000 description 3
- 238000009835 boiling Methods 0.000 description 3
- 150000001768 cations Chemical class 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 239000003480 eluent Substances 0.000 description 3
- KMIXQRTUEYLWJW-UHFFFAOYSA-N ethyl 4-[3-[4-(2-methylimidazol-1-yl)phenyl]sulfanylphenyl]oxane-4-carboxylate Chemical compound C=1C=CC(SC=2C=CC(=CC=2)N2C(=NC=C2)C)=CC=1C1(C(=O)OCC)CCOCC1 KMIXQRTUEYLWJW-UHFFFAOYSA-N 0.000 description 3
- 239000000706 filtrate Substances 0.000 description 3
- 229910052736 halogen Inorganic materials 0.000 description 3
- 150000002367 halogens Chemical class 0.000 description 3
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 3
- 150000002617 leukotrienes Chemical class 0.000 description 3
- XOOLAAFGXNPXTM-UHFFFAOYSA-N methyl 1-(3-fluoro-5-hydroxyphenyl)cyclopent-3-ene-1-carboxylate Chemical compound C=1C(O)=CC(F)=CC=1C1(C(=O)OC)CC=CC1 XOOLAAFGXNPXTM-UHFFFAOYSA-N 0.000 description 3
- KTJFGMKBXRSHFX-UHFFFAOYSA-N methyl 2-(3-fluoro-5-methoxyphenyl)acetate Chemical compound COC(=O)CC1=CC(F)=CC(OC)=C1 KTJFGMKBXRSHFX-UHFFFAOYSA-N 0.000 description 3
- 231100000252 nontoxic Toxicity 0.000 description 3
- 230000003000 nontoxic effect Effects 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 3
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 3
- 239000007858 starting material Substances 0.000 description 3
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 description 3
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 3
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 3
- 239000003039 volatile agent Substances 0.000 description 3
- VEFLKXRACNJHOV-UHFFFAOYSA-N 1,3-dibromopropane Chemical compound BrCCCBr VEFLKXRACNJHOV-UHFFFAOYSA-N 0.000 description 2
- MAHOXXDXOABQRA-UHFFFAOYSA-N 1-(3-hydroxyphenyl)cyclobutane-1-carbonitrile Chemical compound OC1=CC=CC(C2(CCC2)C#N)=C1 MAHOXXDXOABQRA-UHFFFAOYSA-N 0.000 description 2
- QYTPZHFPGSBJJU-UHFFFAOYSA-N 1-(3-hydroxyphenyl)cyclopentane-1-carboxamide Chemical compound C=1C=CC(O)=CC=1C1(C(=O)N)CCCC1 QYTPZHFPGSBJJU-UHFFFAOYSA-N 0.000 description 2
- MFGRIOOSDBSHEH-UHFFFAOYSA-N 1-(3-methoxyphenyl)cyclobutane-1-carbonitrile Chemical compound COC1=CC=CC(C2(CCC2)C#N)=C1 MFGRIOOSDBSHEH-UHFFFAOYSA-N 0.000 description 2
- DRFXZRYABQRQKL-UHFFFAOYSA-N 1-(3-phenylmethoxyphenyl)cyclopentane-1-carboxamide Chemical compound C=1C=CC(OCC=2C=CC=CC=2)=CC=1C1(C(=O)N)CCCC1 DRFXZRYABQRQKL-UHFFFAOYSA-N 0.000 description 2
- AJKXUHOXMDFHMT-UHFFFAOYSA-N 1-(3-phenylmethoxyphenyl)cyclopentane-1-carboxylic acid Chemical compound C=1C=CC(OCC=2C=CC=CC=2)=CC=1C1(C(=O)O)CCCC1 AJKXUHOXMDFHMT-UHFFFAOYSA-N 0.000 description 2
- QDTRSEIQLUCHCN-UHFFFAOYSA-N 1-(4-iodophenyl)-2-methylpyrrole Chemical compound CC1=CC=CN1C1=CC=C(I)C=C1 QDTRSEIQLUCHCN-UHFFFAOYSA-N 0.000 description 2
- PIYNWAKVTXLSIM-UHFFFAOYSA-N 1-(4-iodophenyl)-3,5-dimethylpyrazole Chemical compound N1=C(C)C=C(C)N1C1=CC=C(I)C=C1 PIYNWAKVTXLSIM-UHFFFAOYSA-N 0.000 description 2
- HQDZXJSMZTUUMY-UHFFFAOYSA-N 1-[(4-iodophenyl)methyl]-2-methylimidazole Chemical compound CC1=NC=CN1CC1=CC=C(I)C=C1 HQDZXJSMZTUUMY-UHFFFAOYSA-N 0.000 description 2
- CGMGCLQMWGVXRV-UHFFFAOYSA-N 1-[(4-iodophenyl)methyl]-2-methylpyrrole Chemical compound CC1=CC=CN1CC1=CC=C(I)C=C1 CGMGCLQMWGVXRV-UHFFFAOYSA-N 0.000 description 2
- ZORFWHWGGZCSMT-UHFFFAOYSA-N 1-[3-[[4-(2-methylimidazol-1-yl)phenyl]methoxy]phenyl]cyclobutane-1-carboxamide Chemical compound CC1=NC=CN1C(C=C1)=CC=C1COC1=CC=CC(C2(CCC2)C(N)=O)=C1 ZORFWHWGGZCSMT-UHFFFAOYSA-N 0.000 description 2
- UCWPELULWQUIRP-UHFFFAOYSA-N 1-[3-[[4-(2-methylimidazol-1-yl)phenyl]methoxy]phenyl]cyclopentane-1-carboxamide Chemical compound CC1=NC=CN1C(C=C1)=CC=C1COC1=CC=CC(C2(CCCC2)C(N)=O)=C1 UCWPELULWQUIRP-UHFFFAOYSA-N 0.000 description 2
- FSGROFVDIGSDHY-UHFFFAOYSA-N 1-[3-fluoro-5-[[4-(2-methylimidazol-1-yl)phenyl]methoxy]phenyl]cyclohexane-1-carboxamide Chemical compound CC1=NC=CN1C(C=C1)=CC=C1COC1=CC(F)=CC(C2(CCCCC2)C(N)=O)=C1 FSGROFVDIGSDHY-UHFFFAOYSA-N 0.000 description 2
- AWLNONQBBBMXRT-UHFFFAOYSA-N 1-[3-fluoro-5-[[4-(2-methylimidazol-1-yl)phenyl]methoxy]phenyl]cyclopent-3-ene-1-carboxamide Chemical compound CC1=NC=CN1C(C=C1)=CC=C1COC1=CC(F)=CC(C2(CC=CC2)C(N)=O)=C1 AWLNONQBBBMXRT-UHFFFAOYSA-N 0.000 description 2
- VIWJWEIHVQGHIC-UHFFFAOYSA-N 1-[3-fluoro-5-[[4-(2-methylimidazol-1-yl)phenyl]methoxy]phenyl]cyclopentane-1-carboxamide Chemical compound CC1=NC=CN1C(C=C1)=CC=C1COC1=CC(F)=CC(C2(CCCC2)C(N)=O)=C1 VIWJWEIHVQGHIC-UHFFFAOYSA-N 0.000 description 2
- MLFZAFYTJLYHHQ-UHFFFAOYSA-N 1-[4-(3-fluoro-5-phenylmethoxyphenyl)oxan-4-yl]ethanol Chemical compound C=1C(F)=CC(OCC=2C=CC=CC=2)=CC=1C1(C(O)C)CCOCC1 MLFZAFYTJLYHHQ-UHFFFAOYSA-N 0.000 description 2
- FMWGYNCAGXLKEQ-UHFFFAOYSA-N 1-iodo-2-(2-iodoethoxy)propane Chemical compound ICC(C)OCCI FMWGYNCAGXLKEQ-UHFFFAOYSA-N 0.000 description 2
- MNPCCOVNFXDRDA-UHFFFAOYSA-N 2,5-difluoro-3-methoxybenzaldehyde Chemical compound COC1=CC(F)=CC(C=O)=C1F MNPCCOVNFXDRDA-UHFFFAOYSA-N 0.000 description 2
- PXSHJLGMSITNOP-UHFFFAOYSA-N 2-(2,5-difluoro-3-methoxyphenyl)acetonitrile Chemical compound COC1=CC(F)=CC(CC#N)=C1F PXSHJLGMSITNOP-UHFFFAOYSA-N 0.000 description 2
- OBMYMTSBABEPIB-UHFFFAOYSA-N 2-(3,5-difluorophenyl)acetonitrile Chemical compound FC1=CC(F)=CC(CC#N)=C1 OBMYMTSBABEPIB-UHFFFAOYSA-N 0.000 description 2
- TVCXVUHHCUYLGX-UHFFFAOYSA-N 2-Methylpyrrole Chemical compound CC1=CC=CN1 TVCXVUHHCUYLGX-UHFFFAOYSA-N 0.000 description 2
- KPPATEAUQLUXHN-UHFFFAOYSA-N 3-[tert-butyl(dimethyl)silyl]oxy-2,5-difluorobenzaldehyde Chemical compound CC(C)(C)[Si](C)(C)OC1=CC(F)=CC(C=O)=C1F KPPATEAUQLUXHN-UHFFFAOYSA-N 0.000 description 2
- QQHCLIPWQURSGS-UHFFFAOYSA-N 4-(3-bromophenyl)oxane-4-carboxylic acid Chemical compound C=1C=CC(Br)=CC=1C1(C(=O)O)CCOCC1 QQHCLIPWQURSGS-UHFFFAOYSA-N 0.000 description 2
- XVUHZMRCDFIRJV-UHFFFAOYSA-N 4-(3-fluoro-5-methylsulfanylphenyl)oxane-4-carbonitrile Chemical compound CSC1=CC(F)=CC(C2(CCOCC2)C#N)=C1 XVUHZMRCDFIRJV-UHFFFAOYSA-N 0.000 description 2
- ABDLRLCWOZATLF-UHFFFAOYSA-N 4-(3-fluoro-5-methylsulfinylphenyl)oxane-4-carbonitrile Chemical compound CS(=O)C1=CC(F)=CC(C2(CCOCC2)C#N)=C1 ABDLRLCWOZATLF-UHFFFAOYSA-N 0.000 description 2
- HKRGUUAJQFPEDH-UHFFFAOYSA-N 4-(3-fluoro-5-phenylmethoxyphenyl)oxane-4-carboxamide Chemical compound C=1C(F)=CC(OCC=2C=CC=CC=2)=CC=1C1(C(=O)N)CCOCC1 HKRGUUAJQFPEDH-UHFFFAOYSA-N 0.000 description 2
- UCWJMGRCIUDDBT-UHFFFAOYSA-N 4-(3-fluoro-5-phenylmethoxyphenyl)oxane-4-carboxylic acid Chemical compound C=1C(F)=CC(OCC=2C=CC=CC=2)=CC=1C1(C(=O)O)CCOCC1 UCWJMGRCIUDDBT-UHFFFAOYSA-N 0.000 description 2
- AEAROSKQKPMLJX-UHFFFAOYSA-N 4-(3-fluoro-5-sulfanylphenyl)oxane-4-carbonitrile Chemical compound FC1=CC(S)=CC(C2(CCOCC2)C#N)=C1 AEAROSKQKPMLJX-UHFFFAOYSA-N 0.000 description 2
- LKJKLBODADCQDY-UHFFFAOYSA-N 4-(3-hydroxyphenyl)oxane-4-carboxamide Chemical compound C=1C=CC(O)=CC=1C1(C(=O)N)CCOCC1 LKJKLBODADCQDY-UHFFFAOYSA-N 0.000 description 2
- YLCJJYUTPRPDJR-UHFFFAOYSA-N 4-(3-iodophenyl)oxane-4-carbaldehyde Chemical compound IC1=CC=CC(C2(CCOCC2)C=O)=C1 YLCJJYUTPRPDJR-UHFFFAOYSA-N 0.000 description 2
- TTZTXRNGOWNAAP-UHFFFAOYSA-N 4-(3-iodophenyl)oxane-4-carbonitrile Chemical compound IC1=CC=CC(C2(CCOCC2)C#N)=C1 TTZTXRNGOWNAAP-UHFFFAOYSA-N 0.000 description 2
- KGRAWYBGLDBUQE-UHFFFAOYSA-N 4-(3-phenylmethoxyphenyl)oxane-4-carboxamide Chemical compound C=1C=CC(OCC=2C=CC=CC=2)=CC=1C1(C(=O)N)CCOCC1 KGRAWYBGLDBUQE-UHFFFAOYSA-N 0.000 description 2
- HZDKZWNXXVGKOW-UHFFFAOYSA-N 4-(3-phenylmethoxyphenyl)oxane-4-carboxylic acid Chemical compound C=1C=CC(OCC=2C=CC=CC=2)=CC=1C1(C(=O)O)CCOCC1 HZDKZWNXXVGKOW-UHFFFAOYSA-N 0.000 description 2
- USKHQKJGAANGAK-UHFFFAOYSA-N 4-[3-[4-(2-methylimidazol-1-yl)phenyl]sulfanylphenyl]oxane-4-carbaldehyde Chemical compound CC1=NC=CN1C(C=C1)=CC=C1SC1=CC=CC(C2(CCOCC2)C=O)=C1 USKHQKJGAANGAK-UHFFFAOYSA-N 0.000 description 2
- FIRKTYRTLHGFBQ-UHFFFAOYSA-N 4-[3-[4-(3,5-dimethylpyrazol-1-yl)phenyl]sulfanylphenyl]oxane-4-carbonitrile Chemical compound N1=C(C)C=C(C)N1C(C=C1)=CC=C1SC1=CC=CC(C2(CCOCC2)C#N)=C1 FIRKTYRTLHGFBQ-UHFFFAOYSA-N 0.000 description 2
- DOMDKPPHGFELDC-UHFFFAOYSA-N 4-[3-[4-[(2-methylimidazol-1-yl)methyl]phenyl]sulfanylphenyl]oxane-4-carboxylic acid Chemical compound CC1=NC=CN1CC(C=C1)=CC=C1SC1=CC=CC(C2(CCOCC2)C(O)=O)=C1 DOMDKPPHGFELDC-UHFFFAOYSA-N 0.000 description 2
- OQCDQZLOWCSWEU-UHFFFAOYSA-N 4-[3-[[4-(2-methylimidazol-1-yl)phenyl]methoxy]phenyl]oxane-4-carbonitrile Chemical compound CC1=NC=CN1C(C=C1)=CC=C1COC1=CC=CC(C2(CCOCC2)C#N)=C1 OQCDQZLOWCSWEU-UHFFFAOYSA-N 0.000 description 2
- ATNLHINNMQULHQ-UHFFFAOYSA-N 4-[3-fluoro-5-[4-[(2-methylpyrrol-1-yl)methyl]phenyl]sulfanylphenyl]oxane-4-carbonitrile Chemical compound CC1=CC=CN1CC(C=C1)=CC=C1SC1=CC(F)=CC(C2(CCOCC2)C#N)=C1 ATNLHINNMQULHQ-UHFFFAOYSA-N 0.000 description 2
- YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 2
- 206010001052 Acute respiratory distress syndrome Diseases 0.000 description 2
- ATRRKUHOCOJYRX-UHFFFAOYSA-N Ammonium bicarbonate Chemical compound [NH4+].OC([O-])=O ATRRKUHOCOJYRX-UHFFFAOYSA-N 0.000 description 2
- 229910000013 Ammonium bicarbonate Inorganic materials 0.000 description 2
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- 229920002261 Corn starch Polymers 0.000 description 2
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 2
- GKQLYSROISKDLL-UHFFFAOYSA-N EEDQ Chemical compound C1=CC=C2N(C(=O)OCC)C(OCC)C=CC2=C1 GKQLYSROISKDLL-UHFFFAOYSA-N 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 2
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
- 206010061218 Inflammation Diseases 0.000 description 2
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 2
- LSDPWZHWYPCBBB-UHFFFAOYSA-N Methanethiol Chemical compound SC LSDPWZHWYPCBBB-UHFFFAOYSA-N 0.000 description 2
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 2
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 2
- LFTLOKWAGJYHHR-UHFFFAOYSA-N N-methylmorpholine N-oxide Chemical compound CN1(=O)CCOCC1 LFTLOKWAGJYHHR-UHFFFAOYSA-N 0.000 description 2
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
- KFSLWBXXFJQRDL-UHFFFAOYSA-N Peracetic acid Chemical compound CC(=O)OO KFSLWBXXFJQRDL-UHFFFAOYSA-N 0.000 description 2
- 208000013616 Respiratory Distress Syndrome Diseases 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 2
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Natural products NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 2
- XOEGKOWEHCVONH-UHFFFAOYSA-N [4-(2-methylimidazol-1-yl)phenyl]methanol Chemical compound CC1=NC=CN1C1=CC=C(CO)C=C1 XOEGKOWEHCVONH-UHFFFAOYSA-N 0.000 description 2
- AVPGJIYVDXBRBG-UHFFFAOYSA-N [4-(3-fluoro-5-phenylmethoxyphenyl)oxan-4-yl]methanol Chemical compound C=1C(F)=CC(OCC=2C=CC=CC=2)=CC=1C1(CO)CCOCC1 AVPGJIYVDXBRBG-UHFFFAOYSA-N 0.000 description 2
- FWHSWBYSLVKDHL-UHFFFAOYSA-N [4-[3-[4-(2-methylimidazol-1-yl)phenyl]sulfanylphenyl]oxan-4-yl]methanol Chemical compound CC1=NC=CN1C(C=C1)=CC=C1SC1=CC=CC(C2(CO)CCOCC2)=C1 FWHSWBYSLVKDHL-UHFFFAOYSA-N 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 208000011341 adult acute respiratory distress syndrome Diseases 0.000 description 2
- 201000000028 adult respiratory distress syndrome Diseases 0.000 description 2
- 239000003513 alkali Substances 0.000 description 2
- 235000012538 ammonium bicarbonate Nutrition 0.000 description 2
- 239000001099 ammonium carbonate Substances 0.000 description 2
- 239000006286 aqueous extract Substances 0.000 description 2
- 239000007900 aqueous suspension Substances 0.000 description 2
- SIPUZPBQZHNSDW-UHFFFAOYSA-N bis(2-methylpropyl)aluminum Chemical compound CC(C)C[Al]CC(C)C SIPUZPBQZHNSDW-UHFFFAOYSA-N 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- XJHCXCQVJFPJIK-UHFFFAOYSA-M caesium fluoride Chemical compound [F-].[Cs+] XJHCXCQVJFPJIK-UHFFFAOYSA-M 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 238000004587 chromatography analysis Methods 0.000 description 2
- BERDEBHAJNAUOM-UHFFFAOYSA-N copper(i) oxide Chemical compound [Cu]O[Cu] BERDEBHAJNAUOM-UHFFFAOYSA-N 0.000 description 2
- 239000008120 corn starch Substances 0.000 description 2
- 238000005859 coupling reaction Methods 0.000 description 2
- WGLUMOCWFMKWIL-UHFFFAOYSA-N dichloromethane;methanol Chemical compound OC.ClCCl WGLUMOCWFMKWIL-UHFFFAOYSA-N 0.000 description 2
- RZHIALGQQJESEK-UHFFFAOYSA-L dichloronickel;triethylphosphane Chemical compound Cl[Ni]Cl.CCP(CC)CC.CCP(CC)CC RZHIALGQQJESEK-UHFFFAOYSA-L 0.000 description 2
- VDWVLGVIVRGWRG-UHFFFAOYSA-N diethyl 2-(3-fluoro-5-phenylmethoxyphenyl)propanedioate Chemical compound CCOC(=O)C(C(=O)OCC)C1=CC(F)=CC(OCC=2C=CC=CC=2)=C1 VDWVLGVIVRGWRG-UHFFFAOYSA-N 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- WQOXQRCZOLPYPM-UHFFFAOYSA-N dimethyl disulfide Chemical compound CSSC WQOXQRCZOLPYPM-UHFFFAOYSA-N 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- MQYLUDBSQXWNMH-UHFFFAOYSA-N ethyl 1-(3-fluoro-5-hydroxyphenyl)cyclohexane-1-carboxylate Chemical compound C=1C(O)=CC(F)=CC=1C1(C(=O)OCC)CCCCC1 MQYLUDBSQXWNMH-UHFFFAOYSA-N 0.000 description 2
- YIPDINRIKTXIMB-UHFFFAOYSA-N ethyl 1-(3-fluoro-5-hydroxyphenyl)cyclopentane-1-carboxylate Chemical compound C=1C(O)=CC(F)=CC=1C1(C(=O)OCC)CCCC1 YIPDINRIKTXIMB-UHFFFAOYSA-N 0.000 description 2
- IMVIXFGJVUOOSK-UHFFFAOYSA-N ethyl 1-(3-fluoro-5-phenylmethoxyphenyl)cyclohexane-1-carboxylate Chemical compound C=1C(F)=CC(OCC=2C=CC=CC=2)=CC=1C1(C(=O)OCC)CCCCC1 IMVIXFGJVUOOSK-UHFFFAOYSA-N 0.000 description 2
- UYOJGWFINORKMP-UHFFFAOYSA-N ethyl 1-(3-fluoro-5-phenylmethoxyphenyl)cyclopentane-1-carboxylate Chemical compound C=1C(F)=CC(OCC=2C=CC=CC=2)=CC=1C1(C(=O)OCC)CCCC1 UYOJGWFINORKMP-UHFFFAOYSA-N 0.000 description 2
- XALCCHGPVXMSKU-UHFFFAOYSA-N ethyl 1-(3-phenylmethoxyphenyl)cyclopentane-1-carboxylate Chemical compound C=1C=CC(OCC=2C=CC=CC=2)=CC=1C1(C(=O)OCC)CCCC1 XALCCHGPVXMSKU-UHFFFAOYSA-N 0.000 description 2
- FWDLBXKGCBSVNE-UHFFFAOYSA-N ethyl 1-[3-fluoro-5-[[4-(2-methylimidazol-1-yl)phenyl]methoxy]phenyl]cyclohexane-1-carboxylate Chemical compound C=1C(F)=CC(OCC=2C=CC(=CC=2)N2C(=NC=C2)C)=CC=1C1(C(=O)OCC)CCCCC1 FWDLBXKGCBSVNE-UHFFFAOYSA-N 0.000 description 2
- NPAZIHXCKJHCDT-UHFFFAOYSA-N ethyl 1-[3-fluoro-5-[[4-(2-methylimidazol-1-yl)phenyl]methoxy]phenyl]cyclopentane-1-carboxylate Chemical compound C=1C(F)=CC(OCC=2C=CC(=CC=2)N2C(=NC=C2)C)=CC=1C1(C(=O)OCC)CCCC1 NPAZIHXCKJHCDT-UHFFFAOYSA-N 0.000 description 2
- DGYUNNISKYKIDM-UHFFFAOYSA-N ethyl 4-(2-methylimidazol-1-yl)benzoate Chemical compound C1=CC(C(=O)OCC)=CC=C1N1C(C)=NC=C1 DGYUNNISKYKIDM-UHFFFAOYSA-N 0.000 description 2
- GVKOGJQHZDQALH-UHFFFAOYSA-N ethyl 4-(3-bromophenyl)oxane-4-carboxylate Chemical compound C=1C=CC(Br)=CC=1C1(C(=O)OCC)CCOCC1 GVKOGJQHZDQALH-UHFFFAOYSA-N 0.000 description 2
- WPMVFVYUNGUBAD-UHFFFAOYSA-N ethyl 4-[3-[4-[(2-methylimidazol-1-yl)methyl]phenyl]sulfanylphenyl]oxane-4-carboxylate Chemical compound C=1C=CC(SC=2C=CC(CN3C(=NC=C3)C)=CC=2)=CC=1C1(C(=O)OCC)CCOCC1 WPMVFVYUNGUBAD-UHFFFAOYSA-N 0.000 description 2
- OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 2
- 150000004678 hydrides Chemical class 0.000 description 2
- FUKUFMFMCZIRNT-UHFFFAOYSA-N hydron;methanol;chloride Chemical compound Cl.OC FUKUFMFMCZIRNT-UHFFFAOYSA-N 0.000 description 2
- 230000004054 inflammatory process Effects 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 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
- 230000004060 metabolic process Effects 0.000 description 2
- SEZGTMZGDDDWKN-UHFFFAOYSA-N methyl 1-(3-fluoro-5-methoxyphenyl)cyclopent-3-ene-1-carboxylate Chemical compound C=1C(F)=CC(OC)=CC=1C1(C(=O)OC)CC=CC1 SEZGTMZGDDDWKN-UHFFFAOYSA-N 0.000 description 2
- FCPAFOJGUNQYHJ-UHFFFAOYSA-N methyl 2-(2,5-difluoro-3-methoxyphenyl)acetate Chemical compound COC(=O)CC1=CC(F)=CC(OC)=C1F FCPAFOJGUNQYHJ-UHFFFAOYSA-N 0.000 description 2
- ADGPKZYEZJLVTD-UHFFFAOYSA-N methyl 4-(2,5-difluoro-3-hydroxyphenyl)oxane-4-carboxylate Chemical compound C=1C(F)=CC(O)=C(F)C=1C1(C(=O)OC)CCOCC1 ADGPKZYEZJLVTD-UHFFFAOYSA-N 0.000 description 2
- DVGMXFZOOFINNF-UHFFFAOYSA-N methyl 4-(2,5-difluoro-3-methoxyphenyl)oxane-4-carboxylate Chemical compound C=1C(F)=CC(OC)=C(F)C=1C1(C(=O)OC)CCOCC1 DVGMXFZOOFINNF-UHFFFAOYSA-N 0.000 description 2
- MLGOTCRZMIJBMO-UHFFFAOYSA-N methyl 4-(3-sulfanylphenyl)oxane-4-carboxylate Chemical compound C=1C=CC(S)=CC=1C1(C(=O)OC)CCOCC1 MLGOTCRZMIJBMO-UHFFFAOYSA-N 0.000 description 2
- 150000007522 mineralic acids Chemical class 0.000 description 2
- 150000007524 organic acids Chemical class 0.000 description 2
- 239000011698 potassium fluoride Substances 0.000 description 2
- 235000003270 potassium fluoride Nutrition 0.000 description 2
- 230000003389 potentiating effect Effects 0.000 description 2
- 230000002265 prevention Effects 0.000 description 2
- 206010039073 rheumatoid arthritis Diseases 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 229910052710 silicon Inorganic materials 0.000 description 2
- 239000010703 silicon Substances 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 2
- PUZPDOWCWNUUKD-UHFFFAOYSA-M sodium fluoride Chemical compound [F-].[Na+] PUZPDOWCWNUUKD-UHFFFAOYSA-M 0.000 description 2
- JQWHASGSAFIOCM-UHFFFAOYSA-M sodium periodate Chemical compound [Na+].[O-]I(=O)(=O)=O JQWHASGSAFIOCM-UHFFFAOYSA-M 0.000 description 2
- 238000010561 standard procedure Methods 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 239000003826 tablet Substances 0.000 description 2
- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 2
- 125000001544 thienyl group Chemical group 0.000 description 2
- AMIGYDGSJCJWSD-UHFFFAOYSA-N thiocane Chemical group C1CCCSCCC1 AMIGYDGSJCJWSD-UHFFFAOYSA-N 0.000 description 2
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 2
- QAEDZJGFFMLHHQ-UHFFFAOYSA-N trifluoroacetic anhydride Chemical compound FC(F)(F)C(=O)OC(=O)C(F)(F)F QAEDZJGFFMLHHQ-UHFFFAOYSA-N 0.000 description 2
- 125000000025 triisopropylsilyl group Chemical group C(C)(C)[Si](C(C)C)(C(C)C)* 0.000 description 2
- ONDSBJMLAHVLMI-UHFFFAOYSA-N trimethylsilyldiazomethane Chemical compound C[Si](C)(C)[CH-][N+]#N ONDSBJMLAHVLMI-UHFFFAOYSA-N 0.000 description 2
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 2
- BEULXPIHPUYQCO-UHFFFAOYSA-N (3-phenylmethoxyphenyl) acetate Chemical compound CC(=O)OC1=CC=CC(OCC=2C=CC=CC=2)=C1 BEULXPIHPUYQCO-UHFFFAOYSA-N 0.000 description 1
- IRSLBPNEXYONIQ-WXXKFALUSA-N (E)-but-2-enedioic acid 4-[3-[4-(2-methylimidazol-1-yl)phenyl]sulfanylphenyl]oxane-4-carboxamide Chemical compound OC(=O)\C=C\C(O)=O.Cc1nccn1-c1ccc(Sc2cccc(c2)C2(CCOCC2)C(N)=O)cc1.Cc1nccn1-c1ccc(Sc2cccc(c2)C2(CCOCC2)C(N)=O)cc1 IRSLBPNEXYONIQ-WXXKFALUSA-N 0.000 description 1
- FQDIANVAWVHZIR-UPHRSURJSA-N (z)-1,4-dichlorobut-2-ene Chemical compound ClC\C=C/CCl FQDIANVAWVHZIR-UPHRSURJSA-N 0.000 description 1
- PAAZPARNPHGIKF-UHFFFAOYSA-N 1,2-dibromoethane Chemical compound BrCCBr PAAZPARNPHGIKF-UHFFFAOYSA-N 0.000 description 1
- ULTHEAFYOOPTTB-UHFFFAOYSA-N 1,4-dibromobutane Chemical compound BrCCCCBr ULTHEAFYOOPTTB-UHFFFAOYSA-N 0.000 description 1
- PZPWGUJTIZXBKR-UHFFFAOYSA-N 1,4-dibromohexane Chemical compound CCC(Br)CCCBr PZPWGUJTIZXBKR-UHFFFAOYSA-N 0.000 description 1
- IBODDUNKEPPBKW-UHFFFAOYSA-N 1,5-dibromopentane Chemical compound BrCCCCCBr IBODDUNKEPPBKW-UHFFFAOYSA-N 0.000 description 1
- BQTRMYJYYNQQGK-UHFFFAOYSA-N 1-(bromomethyl)-4-iodobenzene Chemical compound BrCC1=CC=C(I)C=C1 BQTRMYJYYNQQGK-UHFFFAOYSA-N 0.000 description 1
- HUVIWCSDBMZVNQ-UHFFFAOYSA-N 1-[3-[[4-(2-methylimidazol-1-yl)phenyl]methoxy]phenyl]cyclobutane-1-carbonitrile Chemical compound CC1=NC=CN1C(C=C1)=CC=C1COC1=CC=CC(C2(CCC2)C#N)=C1 HUVIWCSDBMZVNQ-UHFFFAOYSA-N 0.000 description 1
- RQCARZNHWVYMPB-UHFFFAOYSA-N 1-[3-[[4-(2-methylimidazol-1-yl)phenyl]methoxy]phenyl]cyclopropane-1-carboxamide Chemical compound CC1=NC=CN1C(C=C1)=CC=C1COC1=CC=CC(C2(CC2)C(N)=O)=C1 RQCARZNHWVYMPB-UHFFFAOYSA-N 0.000 description 1
- YEATUYGBRMGLAA-UHFFFAOYSA-N 1-[4-(3-fluoro-5-hydroxyphenyl)oxan-4-yl]ethanone Chemical compound C=1C(O)=CC(F)=CC=1C1(C(=O)C)CCOCC1 YEATUYGBRMGLAA-UHFFFAOYSA-N 0.000 description 1
- ZSFCHLYYIVAMTH-UHFFFAOYSA-N 1-[4-(3-iodophenyl)oxan-4-yl]-n-methoxymethanimine Chemical compound C=1C=CC(I)=CC=1C1(C=NOC)CCOCC1 ZSFCHLYYIVAMTH-UHFFFAOYSA-N 0.000 description 1
- DSLJUDBXGLZDFU-UHFFFAOYSA-N 1-[4-(chloromethyl)-3-fluorophenyl]-2-methylimidazole;hydrochloride Chemical compound Cl.CC1=NC=CN1C1=CC=C(CCl)C(F)=C1 DSLJUDBXGLZDFU-UHFFFAOYSA-N 0.000 description 1
- ATUJZGJQIULKKC-UHFFFAOYSA-N 1-[4-(chloromethyl)phenyl]-2-methylimidazole Chemical compound CC1=NC=CN1C1=CC=C(CCl)C=C1 ATUJZGJQIULKKC-UHFFFAOYSA-N 0.000 description 1
- STXVJXDZKPQFSK-UHFFFAOYSA-N 1-[4-[3-fluoro-5-[[4-(2-methylimidazol-1-yl)phenyl]methoxy]phenyl]oxan-4-yl]ethanone Chemical compound C=1C(F)=CC(OCC=2C=CC(=CC=2)N2C(=NC=C2)C)=CC=1C1(C(=O)C)CCOCC1 STXVJXDZKPQFSK-UHFFFAOYSA-N 0.000 description 1
- GNKNCAKNJIQBSX-UHFFFAOYSA-N 1-bromo-3-fluoro-5-phenylmethoxybenzene Chemical compound FC1=CC(Br)=CC(OCC=2C=CC=CC=2)=C1 GNKNCAKNJIQBSX-UHFFFAOYSA-N 0.000 description 1
- KGNQDBQYEBMPFZ-UHFFFAOYSA-N 1-fluoro-4-iodobenzene Chemical compound FC1=CC=C(I)C=C1 KGNQDBQYEBMPFZ-UHFFFAOYSA-N 0.000 description 1
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- INXKVYFOWNAVMU-UHFFFAOYSA-N 2,5-difluorophenol Chemical compound OC1=CC(F)=CC=C1F INXKVYFOWNAVMU-UHFFFAOYSA-N 0.000 description 1
- SEMQRDALJZRUCH-UHFFFAOYSA-N 2-[1-(4-methylphenyl)sulfonyloxypropan-2-yloxy]ethyl 4-methylbenzenesulfonate Chemical compound C=1C=C(C)C=CC=1S(=O)(=O)OCCOC(C)COS(=O)(=O)C1=CC=C(C)C=C1 SEMQRDALJZRUCH-UHFFFAOYSA-N 0.000 description 1
- PBFLRUWJYRJLHN-UHFFFAOYSA-N 2-ethyl-2-[3-[4-(2-methylimidazol-1-yl)phenyl]sulfanylphenyl]oxane-4-carboxylic acid Chemical compound C=1C=CC(SC=2C=CC(=CC=2)N2C(=NC=C2)C)=CC=1C1(CC)CC(C(O)=O)CCO1 PBFLRUWJYRJLHN-UHFFFAOYSA-N 0.000 description 1
- HUPNQNOWXCVQSW-UHFFFAOYSA-N 2h-pyran-4-carboxamide Chemical compound NC(=O)C1=CCOC=C1 HUPNQNOWXCVQSW-UHFFFAOYSA-N 0.000 description 1
- SDXAWLJRERMRKF-UHFFFAOYSA-N 3,5-dimethyl-1h-pyrazole Chemical compound CC=1C=C(C)NN=1 SDXAWLJRERMRKF-UHFFFAOYSA-N 0.000 description 1
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 1
- YQDNBVODWMMCMI-UHFFFAOYSA-N 3-fluoro-5-[4-(1-hydroxyethyl)oxan-4-yl]phenol Chemical compound C=1C(O)=CC(F)=CC=1C1(C(O)C)CCOCC1 YQDNBVODWMMCMI-UHFFFAOYSA-N 0.000 description 1
- MCSXGCZMEPXKIW-UHFFFAOYSA-N 3-hydroxy-4-[(4-methyl-2-nitrophenyl)diazenyl]-N-(3-nitrophenyl)naphthalene-2-carboxamide Chemical compound Cc1ccc(N=Nc2c(O)c(cc3ccccc23)C(=O)Nc2cccc(c2)[N+]([O-])=O)c(c1)[N+]([O-])=O MCSXGCZMEPXKIW-UHFFFAOYSA-N 0.000 description 1
- ZJPVGPYUEMYAHG-UHFFFAOYSA-N 4-(3,5-difluorophenyl)oxane-4-carbonitrile Chemical compound FC1=CC(F)=CC(C2(CCOCC2)C#N)=C1 ZJPVGPYUEMYAHG-UHFFFAOYSA-N 0.000 description 1
- XTZCPUGFQPLPOR-UHFFFAOYSA-N 4-(3-fluoro-5-hydroxyphenyl)oxane-2-carboxamide Chemical compound C1COC(C(=O)N)CC1C1=CC(O)=CC(F)=C1 XTZCPUGFQPLPOR-UHFFFAOYSA-N 0.000 description 1
- LYRGWCOJVRMVCH-UHFFFAOYSA-N 4-(3-fluoro-5-hydroxyphenyl)oxane-4-carboxamide Chemical compound C=1C(O)=CC(F)=CC=1C1(C(=O)N)CCOCC1 LYRGWCOJVRMVCH-UHFFFAOYSA-N 0.000 description 1
- WNBOCZRVUIQNKN-UHFFFAOYSA-N 4-(3-methylsulfanylphenyl)oxane-4-carbonitrile Chemical compound CSC1=CC=CC(C2(CCOCC2)C#N)=C1 WNBOCZRVUIQNKN-UHFFFAOYSA-N 0.000 description 1
- OTJKGPSREXOYGA-UHFFFAOYSA-N 4-(3-methylsulfinylphenyl)oxane-4-carbonitrile Chemical compound CS(=O)C1=CC=CC(C2(CCOCC2)C#N)=C1 OTJKGPSREXOYGA-UHFFFAOYSA-N 0.000 description 1
- YTIZWSPMOQMQEV-UHFFFAOYSA-N 4-(3-sulfanylphenyl)oxane-4-carbonitrile Chemical compound SC1=CC=CC(C2(CCOCC2)C#N)=C1 YTIZWSPMOQMQEV-UHFFFAOYSA-N 0.000 description 1
- QOZRMBBTTGJVHA-UHFFFAOYSA-N 4-(4-iodophenyl)-2h-triazole Chemical compound C1=CC(I)=CC=C1C1=CNN=N1 QOZRMBBTTGJVHA-UHFFFAOYSA-N 0.000 description 1
- BSXGFEQKOSBDJJ-UHFFFAOYSA-N 4-[2,5-difluoro-3-[[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)=C1F BSXGFEQKOSBDJJ-UHFFFAOYSA-N 0.000 description 1
- MZQKAIVCVPFFJT-UHFFFAOYSA-N 4-[3-[4-(1,2,4-triazol-4-yl)phenyl]sulfanylphenyl]oxane-4-carbonitrile Chemical compound C=1C=CC(SC=2C=CC(=CC=2)N2C=NN=C2)=CC=1C1(C#N)CCOCC1 MZQKAIVCVPFFJT-UHFFFAOYSA-N 0.000 description 1
- OAENAOUSLZQJLJ-UHFFFAOYSA-N 4-[3-[4-(2-methylimidazol-1-yl)phenoxy]phenyl]oxane-4-carboxamide Chemical compound CC1=NC=CN1C(C=C1)=CC=C1OC1=CC=CC(C2(CCOCC2)C(N)=O)=C1 OAENAOUSLZQJLJ-UHFFFAOYSA-N 0.000 description 1
- BYIYZITWHPGRRV-UHFFFAOYSA-N 4-[3-[4-(2-methylimidazol-1-yl)phenyl]sulfanylphenyl]oxane-4-carboxamide;hydrochloride Chemical compound Cl.CC1=NC=CN1C(C=C1)=CC=C1SC1=CC=CC(C2(CCOCC2)C(N)=O)=C1 BYIYZITWHPGRRV-UHFFFAOYSA-N 0.000 description 1
- DMDCAXAXTXVEND-UHFFFAOYSA-N 4-[3-[4-(2-methylimidazol-1-yl)phenyl]sulfonylphenyl]oxane-4-carboxamide Chemical compound CC1=NC=CN1C1=CC=C(S(=O)(=O)C=2C=C(C=CC=2)C2(CCOCC2)C(N)=O)C=C1 DMDCAXAXTXVEND-UHFFFAOYSA-N 0.000 description 1
- DWBSFAAOBMSGSX-UHFFFAOYSA-N 4-[3-[[4-(2-methylimidazol-1-yl)phenyl]methoxy]phenyl]oxane-4-carboxamide Chemical compound CC1=NC=CN1C(C=C1)=CC=C1COC1=CC=CC(C2(CCOCC2)C(N)=O)=C1 DWBSFAAOBMSGSX-UHFFFAOYSA-N 0.000 description 1
- NPACJMNKWJSIJU-UHFFFAOYSA-N 4-[3-fluoro-5-[4-(2-methylimidazol-1-yl)phenyl]sulfanylphenyl]oxane-4-carboxamide Chemical compound CC1=NC=CN1C(C=C1)=CC=C1SC1=CC(F)=CC(C2(CCOCC2)C(N)=O)=C1 NPACJMNKWJSIJU-UHFFFAOYSA-N 0.000 description 1
- MNRBMMDXHFZNCM-UHFFFAOYSA-N 4-[3-fluoro-5-[4-(2-methylpyrrol-1-yl)phenyl]sulfanylphenyl]oxane-4-carboxamide Chemical compound CC1=CC=CN1C(C=C1)=CC=C1SC1=CC(F)=CC(C2(CCOCC2)C(N)=O)=C1 MNRBMMDXHFZNCM-UHFFFAOYSA-N 0.000 description 1
- YINFRIIHQLEFSC-UHFFFAOYSA-N 4-[3-fluoro-5-[4-[(2-methylpyrrol-1-yl)methyl]phenyl]sulfanylphenyl]oxane-4-carboxamide Chemical compound CC1=CC=CN1CC(C=C1)=CC=C1SC1=CC(F)=CC(C2(CCOCC2)C(N)=O)=C1 YINFRIIHQLEFSC-UHFFFAOYSA-N 0.000 description 1
- IPCQBIDHAOVNPK-UHFFFAOYSA-N 4-[3-fluoro-5-[[4-(2-methylimidazol-1-yl)phenyl]methoxy]phenyl]-n,n-dimethyloxane-4-carboxamide Chemical compound C=1C(F)=CC(OCC=2C=CC(=CC=2)N2C(=NC=C2)C)=CC=1C1(C(=O)N(C)C)CCOCC1 IPCQBIDHAOVNPK-UHFFFAOYSA-N 0.000 description 1
- FSJLPZWUQPVFLZ-UHFFFAOYSA-N 4-[3-fluoro-5-[[4-(2-methylimidazol-1-yl)phenyl]methoxy]phenyl]-n-methyloxane-4-carboxamide Chemical compound C=1C(F)=CC(OCC=2C=CC(=CC=2)N2C(=NC=C2)C)=CC=1C1(C(=O)NC)CCOCC1 FSJLPZWUQPVFLZ-UHFFFAOYSA-N 0.000 description 1
- NWHQLIJWPMSAKB-UHFFFAOYSA-N 4-[3-fluoro-5-[[4-(2-methylimidazol-1-yl)phenyl]methoxy]phenyl]oxane-4-carbothioamide Chemical compound CC1=NC=CN1C(C=C1)=CC=C1COC1=CC(F)=CC(C2(CCOCC2)C(N)=S)=C1 NWHQLIJWPMSAKB-UHFFFAOYSA-N 0.000 description 1
- VLVCDUSVTXIWGW-UHFFFAOYSA-N 4-iodoaniline Chemical compound NC1=CC=C(I)C=C1 VLVCDUSVTXIWGW-UHFFFAOYSA-N 0.000 description 1
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 201000001320 Atherosclerosis Diseases 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- 229910021589 Copper(I) bromide Inorganic materials 0.000 description 1
- 229910021591 Copper(I) chloride Inorganic materials 0.000 description 1
- 229910021595 Copper(I) iodide Inorganic materials 0.000 description 1
- 208000011231 Crohn disease Diseases 0.000 description 1
- DSLZVSRJTYRBFB-LLEIAEIESA-N D-glucaric acid Chemical compound OC(=O)[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O DSLZVSRJTYRBFB-LLEIAEIESA-N 0.000 description 1
- RGHNJXZEOKUKBD-SQOUGZDYSA-M D-gluconate Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O RGHNJXZEOKUKBD-SQOUGZDYSA-M 0.000 description 1
- 206010012438 Dermatitis atopic Diseases 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- 244000166102 Eucalyptus leucoxylon Species 0.000 description 1
- 235000004694 Eucalyptus leucoxylon Nutrition 0.000 description 1
- 206010015866 Extravasation Diseases 0.000 description 1
- 206010018364 Glomerulonephritis Diseases 0.000 description 1
- 201000005569 Gout Diseases 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
- 208000022559 Inflammatory bowel disease Diseases 0.000 description 1
- 102100037611 Lysophospholipase Human genes 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
- 229910002651 NO3 Inorganic materials 0.000 description 1
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 1
- VEQPNABPJHWNSG-UHFFFAOYSA-N Nickel(2+) Chemical compound [Ni+2] VEQPNABPJHWNSG-UHFFFAOYSA-N 0.000 description 1
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
- 108010058864 Phospholipases A2 Proteins 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 102000004005 Prostaglandin-endoperoxide synthases Human genes 0.000 description 1
- 108090000459 Prostaglandin-endoperoxide synthases Proteins 0.000 description 1
- 201000004681 Psoriasis Diseases 0.000 description 1
- 206010039085 Rhinitis allergic Diseases 0.000 description 1
- 229910006124 SOCl2 Inorganic materials 0.000 description 1
- 101100545004 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) YSP2 gene Proteins 0.000 description 1
- 206010040070 Septic Shock Diseases 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- OKJPEAGHQZHRQV-UHFFFAOYSA-N Triiodomethane Natural products IC(I)I OKJPEAGHQZHRQV-UHFFFAOYSA-N 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 150000001335 aliphatic alkanes Chemical class 0.000 description 1
- 229910001854 alkali hydroxide Inorganic materials 0.000 description 1
- 150000001340 alkali metals Chemical class 0.000 description 1
- 229910001860 alkaline earth metal hydroxide Inorganic materials 0.000 description 1
- 150000004703 alkoxides Chemical class 0.000 description 1
- 201000010105 allergic rhinitis Diseases 0.000 description 1
- YNQLUTRBYVCPMQ-UHFFFAOYSA-N alpha-methyl toluene Natural products CCC1=CC=CC=C1 YNQLUTRBYVCPMQ-UHFFFAOYSA-N 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 239000011260 aqueous acid Substances 0.000 description 1
- 239000003125 aqueous solvent Substances 0.000 description 1
- 229910052786 argon Inorganic materials 0.000 description 1
- 239000012300 argon atmosphere Substances 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- 201000008937 atopic dermatitis Diseases 0.000 description 1
- SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 description 1
- 229940077388 benzenesulfonate Drugs 0.000 description 1
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- YNHIGQDRGKUECZ-UHFFFAOYSA-L bis(triphenylphosphine)palladium(ii) dichloride Chemical compound [Cl-].[Cl-].[Pd+2].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 YNHIGQDRGKUECZ-UHFFFAOYSA-L 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 239000004044 bronchoconstricting agent Substances 0.000 description 1
- 230000003435 bronchoconstrictive effect Effects 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- BRPQOXSCLDDYGP-UHFFFAOYSA-N calcium oxide Chemical compound [O-2].[Ca+2] BRPQOXSCLDDYGP-UHFFFAOYSA-N 0.000 description 1
- 239000000292 calcium oxide Substances 0.000 description 1
- ODINCKMPIJJUCX-UHFFFAOYSA-N calcium oxide Inorganic materials [Ca]=O ODINCKMPIJJUCX-UHFFFAOYSA-N 0.000 description 1
- 230000004856 capillary permeability Effects 0.000 description 1
- 150000003857 carboxamides Chemical class 0.000 description 1
- 150000007942 carboxylates Chemical class 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- KXZJHVJKXJLBKO-UHFFFAOYSA-N chembl1408157 Chemical compound N=1C2=CC=CC=C2C(C(=O)O)=CC=1C1=CC=C(O)C=C1 KXZJHVJKXJLBKO-UHFFFAOYSA-N 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 239000003638 chemical reducing agent Substances 0.000 description 1
- 230000003399 chemotactic effect Effects 0.000 description 1
- 238000010568 chiral column chromatography Methods 0.000 description 1
- 238000011097 chromatography purification Methods 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 239000010949 copper Substances 0.000 description 1
- OXBLHERUFWYNTN-UHFFFAOYSA-M copper(I) chloride Chemical compound [Cu]Cl OXBLHERUFWYNTN-UHFFFAOYSA-M 0.000 description 1
- NKNDPYCGAZPOFS-UHFFFAOYSA-M copper(i) bromide Chemical compound Br[Cu] NKNDPYCGAZPOFS-UHFFFAOYSA-M 0.000 description 1
- LSXDOTMGLUJQCM-UHFFFAOYSA-M copper(i) iodide Chemical compound I[Cu] LSXDOTMGLUJQCM-UHFFFAOYSA-M 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- XVSYDLITVYBCBD-UHFFFAOYSA-M cyclopent-3-ene-1-carboxylate Chemical compound [O-]C(=O)C1CC=CC1 XVSYDLITVYBCBD-UHFFFAOYSA-M 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- ZWWWLCMDTZFSOO-UHFFFAOYSA-N diethoxyphosphorylformonitrile Chemical compound CCOP(=O)(C#N)OCC ZWWWLCMDTZFSOO-UHFFFAOYSA-N 0.000 description 1
- FAMRKDQNMBBFBR-BQYQJAHWSA-N diethyl azodicarboxylate Substances CCOC(=O)\N=N\C(=O)OCC FAMRKDQNMBBFBR-BQYQJAHWSA-N 0.000 description 1
- XHFGWHUWQXTGAT-UHFFFAOYSA-N dimethylamine hydrochloride Natural products CNC(C)C XHFGWHUWQXTGAT-UHFFFAOYSA-N 0.000 description 1
- IQDGSYLLQPDQDV-UHFFFAOYSA-N dimethylazanium;chloride Chemical compound Cl.CNC IQDGSYLLQPDQDV-UHFFFAOYSA-N 0.000 description 1
- JZBWUTVDIDNCMW-UHFFFAOYSA-L dipotassium;oxido sulfate Chemical compound [K+].[K+].[O-]OS([O-])(=O)=O JZBWUTVDIDNCMW-UHFFFAOYSA-L 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 230000001804 emulsifying effect Effects 0.000 description 1
- KAQKFAOMNZTLHT-VVUHWYTRSA-N epoprostenol Chemical compound O1C(=CCCCC(O)=O)C[C@@H]2[C@@H](/C=C/[C@@H](O)CCCCC)[C@H](O)C[C@@H]21 KAQKFAOMNZTLHT-VVUHWYTRSA-N 0.000 description 1
- 229960001123 epoprostenol Drugs 0.000 description 1
- CAERSDJFKGMKLY-UHFFFAOYSA-N ethyl 2-(3-bromophenyl)acetate Chemical compound CCOC(=O)CC1=CC=CC(Br)=C1 CAERSDJFKGMKLY-UHFFFAOYSA-N 0.000 description 1
- AJQLFAIAETWMBR-UHFFFAOYSA-N ethyl 4-[3-[4-(pyrrol-1-ylmethyl)phenyl]sulfanylphenyl]oxane-4-carboxylate Chemical compound C=1C=CC(SC=2C=CC(CN3C=CC=C3)=CC=2)=CC=1C1(C(=O)OCC)CCOCC1 AJQLFAIAETWMBR-UHFFFAOYSA-N 0.000 description 1
- UMPRJGKLMUDRHL-UHFFFAOYSA-N ethyl 4-fluorobenzoate Chemical compound CCOC(=O)C1=CC=C(F)C=C1 UMPRJGKLMUDRHL-UHFFFAOYSA-N 0.000 description 1
- WDCDAAMJNUHOIY-UHFFFAOYSA-N ethyl acetate;2-propan-2-yloxypropane Chemical compound CCOC(C)=O.CC(C)OC(C)C WDCDAAMJNUHOIY-UHFFFAOYSA-N 0.000 description 1
- FAMRKDQNMBBFBR-UHFFFAOYSA-N ethyl n-ethoxycarbonyliminocarbamate Chemical compound CCOC(=O)N=NC(=O)OCC FAMRKDQNMBBFBR-UHFFFAOYSA-N 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 230000036251 extravasation Effects 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 239000006260 foam Substances 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 238000001640 fractional crystallisation Methods 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 229940050410 gluconate Drugs 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- XNXVOSBNFZWHBV-UHFFFAOYSA-N hydron;o-methylhydroxylamine;chloride Chemical compound Cl.CON XNXVOSBNFZWHBV-UHFFFAOYSA-N 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 230000004941 influx Effects 0.000 description 1
- 208000030603 inherited susceptibility to asthma Diseases 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 239000002198 insoluble material Substances 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 208000028867 ischemia Diseases 0.000 description 1
- 210000000265 leukocyte Anatomy 0.000 description 1
- VNYSSYRCGWBHLG-AMOLWHMGSA-N leukotriene B4 Chemical compound CCCCC\C=C/C[C@@H](O)\C=C\C=C\C=C/[C@@H](O)CCCC(O)=O VNYSSYRCGWBHLG-AMOLWHMGSA-N 0.000 description 1
- GWNVDXQDILPJIG-NXOLIXFESA-N leukotriene C4 Chemical compound CCCCC\C=C/C\C=C/C=C/C=C/[C@H]([C@@H](O)CCCC(O)=O)SC[C@@H](C(=O)NCC(O)=O)NC(=O)CC[C@H](N)C(O)=O GWNVDXQDILPJIG-NXOLIXFESA-N 0.000 description 1
- YEESKJGWJFYOOK-IJHYULJSSA-N leukotriene D4 Chemical compound CCCCC\C=C/C\C=C/C=C/C=C/[C@H]([C@@H](O)CCCC(O)=O)SC[C@H](N)C(=O)NCC(O)=O YEESKJGWJFYOOK-IJHYULJSSA-N 0.000 description 1
- OTZRAYGBFWZKMX-JUDRUQEKSA-N leukotriene E4 Chemical compound CCCCCC=CCC=C\C=C\C=C\[C@@H](SC[C@H](N)C(O)=O)[C@@H](O)CCCC(O)=O OTZRAYGBFWZKMX-JUDRUQEKSA-N 0.000 description 1
- 239000012280 lithium aluminium hydride Substances 0.000 description 1
- WGOPGODQLGJZGL-UHFFFAOYSA-N lithium;butane Chemical compound [Li+].CC[CH-]C WGOPGODQLGJZGL-UHFFFAOYSA-N 0.000 description 1
- 239000007937 lozenge Substances 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- NXPHGHWWQRMDIA-UHFFFAOYSA-M magnesium;carbanide;bromide Chemical compound [CH3-].[Mg+2].[Br-] NXPHGHWWQRMDIA-UHFFFAOYSA-M 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
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 210000004379 membrane Anatomy 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- RODPSTFPVANRNN-UHFFFAOYSA-N methyl 1-(5-fluoro-5-methoxycyclohexa-1,3-dien-1-yl)cyclopent-3-ene-1-carboxylate Chemical compound C=1C=CC(F)(OC)CC=1C1(C(=O)OC)CC=CC1 RODPSTFPVANRNN-UHFFFAOYSA-N 0.000 description 1
- PKMDIVSLKFUBIS-UHFFFAOYSA-N methyl 2-(3-fluoro-5-hydroxyphenyl)acetate Chemical compound COC(=O)CC1=CC(O)=CC(F)=C1 PKMDIVSLKFUBIS-UHFFFAOYSA-N 0.000 description 1
- ZILWQRRUPKPOIL-UHFFFAOYSA-N methyl 4-(3-methylsulfinylphenyl)oxane-4-carboxylate Chemical compound C=1C=CC(S(C)=O)=CC=1C1(C(=O)OC)CCOCC1 ZILWQRRUPKPOIL-UHFFFAOYSA-N 0.000 description 1
- FMYXUDPFYJZPFZ-UHFFFAOYSA-N methyl 4-[3-[4-(2-methylimidazol-1-yl)phenyl]sulfanylphenyl]oxane-4-carboxylate Chemical compound C=1C=CC(SC=2C=CC(=CC=2)N2C(=NC=C2)C)=CC=1C1(C(=O)OC)CCOCC1 FMYXUDPFYJZPFZ-UHFFFAOYSA-N 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 239000003595 mist Substances 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 239000002808 molecular sieve Substances 0.000 description 1
- 230000003680 myocardial damage Effects 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
- AWKVILIXLHVCCH-UHFFFAOYSA-N n-[[4-[3-[4-(2-methylimidazol-1-yl)phenyl]sulfanylphenyl]oxan-4-yl]methylidene]hydroxylamine Chemical compound CC1=NC=CN1C(C=C1)=CC=C1SC1=CC=CC(C2(CCOCC2)C=NO)=C1 AWKVILIXLHVCCH-UHFFFAOYSA-N 0.000 description 1
- 230000000414 obstructive effect Effects 0.000 description 1
- 239000004533 oil dispersion Substances 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 201000008482 osteoarthritis Diseases 0.000 description 1
- 239000007800 oxidant agent Substances 0.000 description 1
- 229940094443 oxytocics prostaglandins Drugs 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- WLJNZVDCPSBLRP-UHFFFAOYSA-N pamoic acid Chemical class C1=CC=C2C(CC=3C4=CC=CC=C4C=C(C=3O)C(=O)O)=C(O)C(C(O)=O)=CC2=C1 WLJNZVDCPSBLRP-UHFFFAOYSA-N 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 230000001991 pathophysiological effect Effects 0.000 description 1
- 210000003200 peritoneal cavity Anatomy 0.000 description 1
- 150000004965 peroxy acids Chemical class 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- 150000003904 phospholipids Chemical class 0.000 description 1
- CYQAYERJWZKYML-UHFFFAOYSA-N phosphorus pentasulfide Chemical compound S1P(S2)(=S)SP3(=S)SP1(=S)SP2(=S)S3 CYQAYERJWZKYML-UHFFFAOYSA-N 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 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
- 159000000001 potassium salts Chemical class 0.000 description 1
- LJCNRYVRMXRIQR-OLXYHTOASA-L potassium sodium L-tartrate Chemical compound [Na+].[K+].[O-]C(=O)[C@H](O)[C@@H](O)C([O-])=O LJCNRYVRMXRIQR-OLXYHTOASA-L 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 150000003180 prostaglandins Chemical class 0.000 description 1
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
- 150000003242 quaternary ammonium salts Chemical class 0.000 description 1
- 208000023504 respiratory system disease Diseases 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 208000017520 skin disease Diseases 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
- 239000012279 sodium borohydride Substances 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 239000011775 sodium fluoride Substances 0.000 description 1
- 235000013024 sodium fluoride Nutrition 0.000 description 1
- 235000011006 sodium potassium tartrate Nutrition 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 230000000707 stereoselective effect Effects 0.000 description 1
- 239000008174 sterile solution Substances 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- SCLRYYDLDQIZJH-UHFFFAOYSA-N tert-butyl-(2,5-difluorophenoxy)-dimethylsilane Chemical compound CC(C)(C)[Si](C)(C)OC1=CC(F)=CC=C1F SCLRYYDLDQIZJH-UHFFFAOYSA-N 0.000 description 1
- BCNZYOJHNLTNEZ-UHFFFAOYSA-N tert-butyldimethylsilyl chloride Chemical compound CC(C)(C)[Si](C)(C)Cl BCNZYOJHNLTNEZ-UHFFFAOYSA-N 0.000 description 1
- 125000001981 tert-butyldimethylsilyl group Chemical group [H]C([H])([H])[Si]([H])(C([H])([H])[H])[*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000000037 tert-butyldiphenylsilyl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1[Si]([H])([*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 150000003595 thromboxanes Chemical class 0.000 description 1
- SYRHIZPPCHMRIT-UHFFFAOYSA-N tin(4+) Chemical group [Sn+4] SYRHIZPPCHMRIT-UHFFFAOYSA-N 0.000 description 1
- CPKHFNMJTBLKLK-UHFFFAOYSA-N tri(propan-2-yl)-sulfanylsilane Chemical compound CC(C)[Si](S)(C(C)C)C(C)C CPKHFNMJTBLKLK-UHFFFAOYSA-N 0.000 description 1
- RYVBINGWVJJDPU-UHFFFAOYSA-M tributyl(hexadecyl)phosphanium;bromide Chemical compound [Br-].CCCCCCCCCCCCCCCC[P+](CCCC)(CCCC)CCCC RYVBINGWVJJDPU-UHFFFAOYSA-M 0.000 description 1
- RXJKFRMDXUJTEX-UHFFFAOYSA-N triethylphosphine Chemical compound CCP(CC)CC RXJKFRMDXUJTEX-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
- 239000005526 vasoconstrictor agent Substances 0.000 description 1
Classifications
-
- 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]
-
- 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
-
- 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
Landscapes
- 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)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Rheumatology (AREA)
- Immunology (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Pain & Pain Management (AREA)
- Pulmonology (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)
- Plural Heterocyclic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (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 (bg) |
JP (1) | JP3032579B2 (bg) |
CN (1) | CN1093536C (bg) |
AT (1) | ATE198474T1 (bg) |
AU (1) | AU681520B2 (bg) |
BG (1) | BG61768B1 (bg) |
CA (1) | CA2202057C (bg) |
CO (1) | CO4480026A1 (bg) |
CZ (1) | CZ287350B6 (bg) |
DE (1) | DE69519804T2 (bg) |
DK (1) | DK0787127T3 (bg) |
ES (1) | ES2153033T3 (bg) |
FI (1) | FI971632A (bg) |
GR (1) | GR3035471T3 (bg) |
HU (1) | HU221543B (bg) |
IL (1) | IL115581A (bg) |
LV (1) | LV11468B (bg) |
MY (1) | MY114680A (bg) |
NO (1) | NO314629B1 (bg) |
NZ (1) | NZ285163A (bg) |
PE (1) | PE49196A1 (bg) |
PL (1) | PL180104B1 (bg) |
RU (1) | RU2136666C1 (bg) |
SI (1) | SI9500392A (bg) |
SK (1) | SK281577B6 (bg) |
TR (1) | TR199501274A2 (bg) |
TW (1) | TW411339B (bg) |
UA (1) | UA45312C2 (bg) |
WO (1) | WO1996011911A1 (bg) |
YU (1) | YU65995A (bg) |
ZA (1) | ZA958748B (bg) |
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 |
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 |
US6344563B1 (en) * | 1999-08-31 | 2002-02-05 | Timothy Norris | Process for making 5-lipoxygenase inhibitors having varied heterocyclic ring systems |
CN1321112C (zh) * | 2000-03-24 | 2007-06-13 | 欧洲凯尔特股份有限公司 | 作为钠通道阻滞剂的芳基取代的吡唑、三唑和四唑化合物 |
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 |
MX2009005526A (es) | 2006-11-27 | 2009-06-05 | Pfizer Prod Inc | Analogos de pirazol. |
WO2009069044A1 (en) | 2007-11-26 | 2009-06-04 | Pfizer Inc. | Pyrazole derivatives as 5-lo inhibitors |
TW201341356A (zh) * | 2012-02-28 | 2013-10-16 | 皮拉馬爾企業有限公司 | 作為gpr促效劑之苯基烷酸衍生物 |
EP3762368B1 (en) | 2018-03-08 | 2022-01-26 | Incyte Corporation | Aminopyrazine diol compounds as pi3k-y inhibitors |
US11046658B2 (en) | 2018-07-02 | 2021-06-29 | Incyte Corporation | Aminopyrazine derivatives as PI3K-γ inhibitors |
Family Cites Families (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
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 |
RU2126004C1 (ru) * | 1993-06-14 | 1999-02-10 | Пфайзер, Инк. | Производные имидазола или их фармацевтически приемлемые соли |
-
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 CA CA002202057A patent/CA2202057C/en not_active Expired - Fee Related
- 1995-05-29 CN CN95195926A patent/CN1093536C/zh not_active Expired - Fee Related
- 1995-05-29 DK DK95918121T patent/DK0787127T3/da active
- 1995-05-29 JP JP8513058A patent/JP3032579B2/ja not_active Expired - Fee Related
- 1995-05-29 PL PL95319727A patent/PL180104B1/pl not_active IP Right Cessation
- 1995-05-29 ES ES95918121T patent/ES2153033T3/es not_active Expired - Lifetime
- 1995-05-29 WO PCT/IB1995/000408 patent/WO1996011911A1/en active IP Right Grant
- 1995-05-29 DE DE69519804T patent/DE69519804T2/de not_active Expired - Fee Related
- 1995-05-29 AU AU24174/95A patent/AU681520B2/en not_active Ceased
- 1995-05-29 HU HU9701853A patent/HU221543B/hu not_active IP Right Cessation
- 1995-05-29 EP EP95918121A patent/EP0787127B1/en not_active Expired - Lifetime
- 1995-05-29 RU RU97106099/04A patent/RU2136666C1/ru not_active IP Right Cessation
- 1995-05-29 AT AT95918121T patent/ATE198474T1/de not_active IP Right Cessation
- 1995-05-29 NZ NZ285163A patent/NZ285163A/en unknown
- 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 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
- 1995-10-17 SI SI9500392A patent/SI9500392A/sl unknown
- 1995-10-17 YU YU65995A patent/YU65995A/sh unknown
- 1995-10-18 TR TR95/01274A patent/TR199501274A2/xx unknown
- 1995-10-18 BG BG100070A patent/BG61768B1/bg unknown
-
1997
- 1997-04-17 FI FI971632A patent/FI971632A/fi not_active IP Right Cessation
- 1997-04-17 NO NO19971773A patent/NO314629B1/no unknown
-
2001
- 2001-02-23 GR GR20010400310T patent/GR3035471T3/el not_active IP Right Cessation
Also Published As
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US5883106A (en) | 5-lipoxygenase inhibitors | |
US5225438A (en) | Aryl derivatives | |
NO314629B1 (no) | 5-lipoksygenase-inhibitorer | |
NO155884B (no) | Analogifremgangsmaate for fremstilling av terapeutisk aktive imidazol-derivater. | |
US6063928A (en) | 5-lipoxygenase inhibitors | |
US5753682A (en) | Imidazole lipoxygenase inhibitors | |
JP3400392B2 (ja) | 5−リポキシゲナーゼ阻害剤及び新規医薬組成物 | |
JP3622882B2 (ja) | トリアゾール誘導体を含有する医薬 | |
KR100239930B1 (ko) | 5-리폭시게나제 저해제 | |
PT787127E (pt) | Inibidores de 5-lipoxigenase | |
JP2843920B2 (ja) | イミダゾールリポキシゲナーゼ阻害剤 | |
JPH05230069A (ja) | 新規なピロロチアゾ−ル誘導体 |