NO319612B1 - Benzopyranderivater som har leukotrien-antagonistisk virkning, fremgangsmate for fremstilling og anvendelse derav - Google Patents

Benzopyranderivater som har leukotrien-antagonistisk virkning, fremgangsmate for fremstilling og anvendelse derav Download PDF

Info

Publication number: NO319612B1
Authority: NO; Norway
Prior art keywords: oxo; benzopyran; compound; phenyl; group
Prior art date: 1996-03-21

Application number

NO19984330A

Other languages

English (en)

Norwegian (no)

Other versions

NO984330D0 (no

NO984330L (no

Inventor

David Mauleon Casellas

Ma Luisa Garcia Perez

Germano Carganico

Jaime Pascual Avellana

Albert Palomer Benet

Original Assignee

Menarini Lab

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

1996-03-21

Filing date

1998-09-17

Publication date

2005-08-29

1998-09-17 Application filed by Menarini Lab filed Critical Menarini Lab

1998-09-17 Publication of NO984330D0 publication Critical patent/NO984330D0/no

1998-10-09 Publication of NO984330L publication Critical patent/NO984330L/no

2005-08-29 Publication of NO319612B1 publication Critical patent/NO319612B1/no

Links

238000000034 method Methods 0.000 title claims description 155
238000002360 preparation method Methods 0.000 title claims description 139
150000002617 leukotrienes Chemical class 0.000 title claims description 15
230000003042 antagnostic effect Effects 0.000 title description 5
150000001562 benzopyrans Chemical class 0.000 title description 5
150000001875 compounds Chemical class 0.000 claims abstract description 309
-1 benzyloxymethyl Chemical group 0.000 claims abstract description 29
125000001424 substituent group Chemical group 0.000 claims abstract description 23
239000003814 drug Substances 0.000 claims abstract description 4
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 58
229910052739 hydrogen Inorganic materials 0.000 claims description 36
239000001257 hydrogen Substances 0.000 claims description 36
125000000623 heterocyclic group Chemical group 0.000 claims description 28
229910052760 oxygen Inorganic materials 0.000 claims description 27
239000001301 oxygen Substances 0.000 claims description 27
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 22
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 21
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 19
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 18
229910052801 chlorine Inorganic materials 0.000 claims description 18
125000004106 butoxy group Chemical group [*]OC([H])([H])C([H])([H])C(C([H])([H])[H])([H])[H] 0.000 claims description 17
239000000460 chlorine Substances 0.000 claims description 17
150000002431 hydrogen Chemical class 0.000 claims description 16
229910052717 sulfur Inorganic materials 0.000 claims description 16
239000002585 base Substances 0.000 claims description 15
125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 claims description 12
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 10
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 10
230000007062 hydrolysis Effects 0.000 claims description 10
238000006460 hydrolysis reaction Methods 0.000 claims description 10
MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 claims description 9
125000000217 alkyl group Chemical group 0.000 claims description 9
125000004434 sulfur atom Chemical group 0.000 claims description 9
PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 claims description 8
239000002253 acid Substances 0.000 claims description 8
239000003513 alkali Substances 0.000 claims description 8
150000003839 salts Chemical class 0.000 claims description 8
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 7
201000010099 disease Diseases 0.000 claims description 7
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 7
239000011593 sulfur Substances 0.000 claims description 7
125000004432 carbon atom Chemical group C* 0.000 claims description 6
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 5
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 5
229910052731 fluorine Inorganic materials 0.000 claims description 5
239000011737 fluorine Substances 0.000 claims description 5
125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims description 5
125000005228 aryl sulfonate group Chemical group 0.000 claims description 4
125000001309 chloro group Chemical group Cl* 0.000 claims description 4
NLFBCYMMUAKCPC-KQQUZDAGSA-N ethyl (e)-3-[3-amino-2-cyano-1-[(e)-3-ethoxy-3-oxoprop-1-enyl]sulfanyl-3-oxoprop-1-enyl]sulfanylprop-2-enoate Chemical compound CCOC(=O)\C=C\SC(=C(C#N)C(N)=O)S\C=C\C(=O)OCC NLFBCYMMUAKCPC-KQQUZDAGSA-N 0.000 claims description 4
230000001404 mediated effect Effects 0.000 claims description 4
125000006239 protecting group Chemical group 0.000 claims description 4
230000001225 therapeutic effect Effects 0.000 claims description 4
FMCAFXHLMUOIGG-IWFBPKFRSA-N (2s)-2-[[(2s)-2-[[(2s)-2-[[(2r)-2-formamido-3-sulfanylpropanoyl]amino]-3-methylbutanoyl]amino]-3-(4-hydroxy-2,5-dimethylphenyl)propanoyl]amino]-4-methylsulfanylbutanoic acid Chemical compound O=CN[C@@H](CS)C(=O)N[C@@H](C(C)C)C(=O)N[C@H](C(=O)N[C@@H](CCSC)C(O)=O)CC1=CC(C)=C(O)C=C1C FMCAFXHLMUOIGG-IWFBPKFRSA-N 0.000 claims description 3
206010002198 Anaphylactic reaction Diseases 0.000 claims description 3
206010003225 Arteriospasm coronary Diseases 0.000 claims description 3
206010048962 Brain oedema Diseases 0.000 claims description 3
206010014824 Endotoxic shock Diseases 0.000 claims description 3
201000004681 Psoriasis Diseases 0.000 claims description 3
206010039085 Rhinitis allergic Diseases 0.000 claims description 3
206010040070 Septic Shock Diseases 0.000 claims description 3
239000005864 Sulphur Substances 0.000 claims description 3
201000010105 allergic rhinitis Diseases 0.000 claims description 3
150000001412 amines Chemical class 0.000 claims description 3
230000036783 anaphylactic response Effects 0.000 claims description 3
208000003455 anaphylaxis Diseases 0.000 claims description 3
208000006673 asthma Diseases 0.000 claims description 3
208000010668 atopic eczema Diseases 0.000 claims description 3
208000006752 brain edema Diseases 0.000 claims description 3
230000000747 cardiac effect Effects 0.000 claims description 3
229940079593 drug Drugs 0.000 claims description 3
229910052736 halogen Inorganic materials 0.000 claims description 3
150000002367 halogens Chemical class 0.000 claims description 3
230000002757 inflammatory effect Effects 0.000 claims description 3
208000030603 inherited susceptibility to asthma Diseases 0.000 claims description 3
NBTOZLQBSIZIKS-UHFFFAOYSA-N methoxide Chemical compound [O-]C NBTOZLQBSIZIKS-UHFFFAOYSA-N 0.000 claims description 3
239000012453 solvate Substances 0.000 claims description 3
RAXLNKSLSXRFJD-UHFFFAOYSA-N 4-oxo-8-[[4-(4-phenylbutoxy)phenyl]methoxy]chromene-2-carboxylic acid Chemical compound C=12OC(C(=O)O)=CC(=O)C2=CC=CC=1OCC(C=C1)=CC=C1OCCCCC1=CC=CC=C1 RAXLNKSLSXRFJD-UHFFFAOYSA-N 0.000 claims description 2
206010006811 Bursitis Diseases 0.000 claims description 2
206010010744 Conjunctivitis allergic Diseases 0.000 claims description 2
208000000491 Tendinopathy Diseases 0.000 claims description 2
206010043255 Tendonitis Diseases 0.000 claims description 2
229910052783 alkali metal Inorganic materials 0.000 claims description 2
229910052784 alkaline earth metal Inorganic materials 0.000 claims description 2
208000002205 allergic conjunctivitis Diseases 0.000 claims description 2
230000000172 allergic effect Effects 0.000 claims description 2
150000003863 ammonium salts Chemical class 0.000 claims description 2
208000024998 atopic conjunctivitis Diseases 0.000 claims description 2
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 2
150000001768 cations Chemical class 0.000 claims description 2
238000003776 cleavage reaction Methods 0.000 claims description 2
238000007796 conventional method Methods 0.000 claims description 2
208000027866 inflammatory disease Diseases 0.000 claims description 2
150000002500 ions Chemical class 0.000 claims description 2
AGJSNMGHAVDLRQ-HUUJSLGLSA-N methyl (2s)-2-[[(2r)-2-[[(2s)-2-[[(2r)-2-amino-3-sulfanylpropanoyl]amino]-3-methylbutanoyl]amino]-3-(4-hydroxy-2,3-dimethylphenyl)propanoyl]amino]-4-methylsulfanylbutanoate Chemical compound SC[C@H](N)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C(=O)N[C@@H](CCSC)C(=O)OC)CC1=CC=C(O)C(C)=C1C AGJSNMGHAVDLRQ-HUUJSLGLSA-N 0.000 claims description 2
208000010125 myocardial infarction Diseases 0.000 claims description 2
208000031225 myocardial ischemia Diseases 0.000 claims description 2
201000008482 osteoarthritis Diseases 0.000 claims description 2
125000003884 phenylalkyl group Chemical group 0.000 claims description 2
230000008569 process Effects 0.000 claims description 2
206010039073 rheumatoid arthritis Diseases 0.000 claims description 2
230000007017 scission Effects 0.000 claims description 2
239000011734 sodium Substances 0.000 claims description 2
201000004415 tendinitis Diseases 0.000 claims description 2
GSEJCLTVZPLZKY-UHFFFAOYSA-O triethanolammonium Chemical compound OCC[NH+](CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-O 0.000 claims description 2
DRDCQJADRSJFFD-UHFFFAOYSA-N tris-hydroxymethyl-methyl-ammonium Chemical compound OC[N+](C)(CO)CO DRDCQJADRSJFFD-UHFFFAOYSA-N 0.000 claims description 2
125000000896 monocarboxylic acid group Chemical group 0.000 claims 3
230000002526 effect on cardiovascular system Effects 0.000 claims 2
FCSKOFQQCWLGMV-UHFFFAOYSA-N 5-{5-[2-chloro-4-(4,5-dihydro-1,3-oxazol-2-yl)phenoxy]pentyl}-3-methylisoxazole Chemical compound O1N=C(C)C=C1CCCCCOC1=CC=C(C=2OCCN=2)C=C1Cl FCSKOFQQCWLGMV-UHFFFAOYSA-N 0.000 claims 1
PYUGFOWNYMLROI-KPKJPENVSA-N 8-[(e)-2-[4-[4-(4-fluorophenyl)butoxy]phenyl]ethenyl]-2-(2h-tetrazol-5-yl)chromen-4-one Chemical compound C1=CC(F)=CC=C1CCCCOC(C=C1)=CC=C1\C=C\C1=CC=CC2=C1OC(C=1NN=NN=1)=CC2=O PYUGFOWNYMLROI-KPKJPENVSA-N 0.000 claims 1
FKLJPTJMIBLJAV-UHFFFAOYSA-N Compound IV Chemical compound O1N=C(C)C=C1CCCCCCCOC1=CC=C(C=2OCCN=2)C=C1 FKLJPTJMIBLJAV-UHFFFAOYSA-N 0.000 claims 1
238000010306 acid treatment Methods 0.000 claims 1
208000026935 allergic disease Diseases 0.000 claims 1
AGJSNMGHAVDLRQ-IWFBPKFRSA-N methyl (2s)-2-[[(2s)-2-[[(2s)-2-[[(2r)-2-amino-3-sulfanylpropanoyl]amino]-3-methylbutanoyl]amino]-3-(4-hydroxy-2,3-dimethylphenyl)propanoyl]amino]-4-methylsulfanylbutanoate Chemical compound SC[C@H](N)C(=O)N[C@@H](C(C)C)C(=O)N[C@H](C(=O)N[C@@H](CCSC)C(=O)OC)CC1=CC=C(O)C(C)=C1C AGJSNMGHAVDLRQ-IWFBPKFRSA-N 0.000 claims 1
230000000694 effects Effects 0.000 abstract description 7
208000024172 Cardiovascular disease Diseases 0.000 abstract description 2
230000003266 anti-allergic effect Effects 0.000 abstract description 2
230000003110 anti-inflammatory effect Effects 0.000 abstract description 2
238000001179 sorption measurement Methods 0.000 abstract description 2
125000006201 3-phenylpropyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])C([H])([H])* 0.000 abstract 1
OTAFHZMPRISVEM-UHFFFAOYSA-N chromone Chemical class C1=CC=C2C(=O)C=COC2=C1 OTAFHZMPRISVEM-UHFFFAOYSA-N 0.000 abstract 1
238000005481 NMR spectroscopy Methods 0.000 description 151
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 150
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 123
239000000203 mixture Substances 0.000 description 122
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 111
239000002904 solvent Substances 0.000 description 82
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 81
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 80
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 75
239000000243 solution Substances 0.000 description 70
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 68
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 63
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 63
239000000741 silica gel Substances 0.000 description 61
229910002027 silica gel Inorganic materials 0.000 description 61
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 60
238000004587 chromatography analysis Methods 0.000 description 58
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 56
239000007787 solid Substances 0.000 description 52
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 39
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 36
239000003208 petroleum Substances 0.000 description 34
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 28
239000007858 starting material Substances 0.000 description 24
238000003756 stirring Methods 0.000 description 23
238000006243 chemical reaction Methods 0.000 description 21
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 18
239000012043 crude product Substances 0.000 description 18
238000002425 crystallisation Methods 0.000 description 18
230000008025 crystallization Effects 0.000 description 18
239000012074 organic phase Substances 0.000 description 18
HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Inorganic materials [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 18
WYACBZDAHNBPPB-UHFFFAOYSA-N diethyl oxalate Chemical compound CCOC(=O)C(=O)OCC WYACBZDAHNBPPB-UHFFFAOYSA-N 0.000 description 17
239000000047 product Substances 0.000 description 17
XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 16
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 15
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 15
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 14
238000001308 synthesis method Methods 0.000 description 13
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 12
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 12
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 11
238000010992 reflux Methods 0.000 description 11
238000001035 drying Methods 0.000 description 10
HJLYHXATZHROAL-UHFFFAOYSA-N 3,4-dihydro-2h-chromene-6-carboxamide Chemical compound O1CCCC2=CC(C(=O)N)=CC=C21 HJLYHXATZHROAL-UHFFFAOYSA-N 0.000 description 9
NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 9
239000000126 substance Substances 0.000 description 9
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 8
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical class [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 8
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-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
AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 8
238000001914 filtration Methods 0.000 description 8
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 8
239000000725 suspension Substances 0.000 description 8
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 7
238000001704 evaporation Methods 0.000 description 7
230000008020 evaporation Effects 0.000 description 7
125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 7
229940002520 2'-hydroxyacetophenone Drugs 0.000 description 6
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 6
239000008346 aqueous phase Substances 0.000 description 6
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical compound BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 6
229910052794 bromium Inorganic materials 0.000 description 6
230000003197 catalytic effect Effects 0.000 description 6
238000010828 elution Methods 0.000 description 6
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 6
239000012071 phase Substances 0.000 description 6
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 6
239000011541 reaction mixture Substances 0.000 description 6
238000012360 testing method Methods 0.000 description 6
PLCGAGSBVAGXMP-UHFFFAOYSA-N 2,3-dihydro-1-benzofuran-3-amine Chemical compound C1=CC=C2C(N)COC2=C1 PLCGAGSBVAGXMP-UHFFFAOYSA-N 0.000 description 5
HBEDSQVIWPRPAY-UHFFFAOYSA-N 2,3-dihydrobenzofuran Chemical group C1=CC=C2OCCC2=C1 HBEDSQVIWPRPAY-UHFFFAOYSA-N 0.000 description 5
JECYUBVRTQDVAT-UHFFFAOYSA-N 2-acetylphenol Chemical compound CC(=O)C1=CC=CC=C1O JECYUBVRTQDVAT-UHFFFAOYSA-N 0.000 description 5
125000003836 4-phenylbutoxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])O* 0.000 description 5
KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 description 5
239000000284 extract Substances 0.000 description 5
230000005764 inhibitory process Effects 0.000 description 5
WMFOQBRAJBCJND-UHFFFAOYSA-M lithium hydroxide Inorganic materials [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 5
238000004519 manufacturing process Methods 0.000 description 5
230000008018 melting Effects 0.000 description 5
238000002844 melting Methods 0.000 description 5
239000012528 membrane Substances 0.000 description 5
230000009467 reduction Effects 0.000 description 5
PTPNOHHWWIGMJD-UHFFFAOYSA-N 1-(2-hydroxy-3-iodophenyl)ethanone Chemical compound CC(=O)C1=CC=CC(I)=C1O PTPNOHHWWIGMJD-UHFFFAOYSA-N 0.000 description 4
125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 4
RGHHSNMVTDWUBI-UHFFFAOYSA-N 4-hydroxybenzaldehyde Chemical compound OC1=CC=C(C=O)C=C1 RGHHSNMVTDWUBI-UHFFFAOYSA-N 0.000 description 4
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 4
LELOWRISYMNNSU-UHFFFAOYSA-N Hydrocyanic acid Natural products N#C LELOWRISYMNNSU-UHFFFAOYSA-N 0.000 description 4
206010061218 Inflammation Diseases 0.000 description 4
MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 4
SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 4
SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 4
230000009471 action Effects 0.000 description 4
229940114079 arachidonic acid Drugs 0.000 description 4
235000021342 arachidonic acid Nutrition 0.000 description 4
ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 description 4
PUSKHXMZPOMNTQ-UHFFFAOYSA-N ethyl 2,1,3-benzoselenadiazole-5-carboxylate Chemical compound CCOC(=O)C1=CC=C2N=[Se]=NC2=C1 PUSKHXMZPOMNTQ-UHFFFAOYSA-N 0.000 description 4
125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 4
230000004054 inflammatory process Effects 0.000 description 4
BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-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
229910000027 potassium carbonate Inorganic materials 0.000 description 4
LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 4
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XLSMFKSTNGKWQX-UHFFFAOYSA-N alpha-hydroxyacetone Natural products CC(=O)CO XLSMFKSTNGKWQX-UHFFFAOYSA-N 0.000 description 1
VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 1
229910021529 ammonia Inorganic materials 0.000 description 1
238000004458 analytical method Methods 0.000 description 1
230000002052 anaphylactic effect Effects 0.000 description 1
239000005557 antagonist Substances 0.000 description 1
229940027991 antiseptic and disinfectant quinoline derivative Drugs 0.000 description 1
238000013459 approach Methods 0.000 description 1
150000004982 aromatic amines Chemical class 0.000 description 1
125000004429 atom Chemical group 0.000 description 1
201000008937 atopic dermatitis Diseases 0.000 description 1
JXLHNMVSKXFWAO-UHFFFAOYSA-N azane;7-fluoro-2,1,3-benzoxadiazole-4-sulfonic acid Chemical compound N.OS(=O)(=O)C1=CC=C(F)C2=NON=C12 JXLHNMVSKXFWAO-UHFFFAOYSA-N 0.000 description 1
WZEMSIKSCALWJZ-UHFFFAOYSA-N azane;ethanol Chemical compound N.CCO.CCO WZEMSIKSCALWJZ-UHFFFAOYSA-N 0.000 description 1
ZXVOCOLRQJZVBW-UHFFFAOYSA-N azane;ethanol Chemical compound N.CCO ZXVOCOLRQJZVBW-UHFFFAOYSA-N 0.000 description 1
230000008901 benefit Effects 0.000 description 1
UENWRTRMUIOCKN-UHFFFAOYSA-N benzyl thiol Chemical compound SCC1=CC=CC=C1 UENWRTRMUIOCKN-UHFFFAOYSA-N 0.000 description 1
210000004369 blood Anatomy 0.000 description 1
239000008280 blood Substances 0.000 description 1
238000009835 boiling Methods 0.000 description 1
229910000085 borane Inorganic materials 0.000 description 1
229910052796 boron Inorganic materials 0.000 description 1
PVYPHUYXKVVURH-UHFFFAOYSA-N boron;2-methylpropan-2-amine Chemical compound [B].CC(C)(C)N PVYPHUYXKVVURH-UHFFFAOYSA-N 0.000 description 1
210000000621 bronchi Anatomy 0.000 description 1
206010006451 bronchitis Diseases 0.000 description 1
239000000872 buffer Substances 0.000 description 1
244000309464 bull Species 0.000 description 1
239000011575 calcium Substances 0.000 description 1
AXCZMVOFGPJBDE-UHFFFAOYSA-L calcium dihydroxide Chemical compound [OH-].[OH-].[Ca+2] AXCZMVOFGPJBDE-UHFFFAOYSA-L 0.000 description 1
239000000920 calcium hydroxide Substances 0.000 description 1
229910001861 calcium hydroxide Inorganic materials 0.000 description 1
239000002775 capsule Substances 0.000 description 1
DXHPZXWIPWDXHJ-UHFFFAOYSA-N carbon monosulfide Chemical compound [S+]#[C-] DXHPZXWIPWDXHJ-UHFFFAOYSA-N 0.000 description 1
150000001733 carboxylic acid esters Chemical class 0.000 description 1
210000004027 cell Anatomy 0.000 description 1
210000000170 cell membrane Anatomy 0.000 description 1
239000003795 chemical substances by application Substances 0.000 description 1
NEHMKBQYUWJMIP-NJFSPNSNSA-N chloro(114C)methane Chemical compound [14CH3]Cl NEHMKBQYUWJMIP-NJFSPNSNSA-N 0.000 description 1
208000007451 chronic bronchitis Diseases 0.000 description 1
238000004440 column chromatography Methods 0.000 description 1
230000002517 constrictor effect Effects 0.000 description 1
230000008602 contraction Effects 0.000 description 1
210000004351 coronary vessel Anatomy 0.000 description 1
XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 1
235000018417 cysteine Nutrition 0.000 description 1
238000010908 decantation Methods 0.000 description 1
238000000354 decomposition reaction Methods 0.000 description 1
230000007850 degeneration Effects 0.000 description 1
238000005695 dehalogenation reaction Methods 0.000 description 1
235000014113 dietary fatty acids Nutrition 0.000 description 1
SGDINNZGYDHHKM-UHFFFAOYSA-N dilithium;trimethylsilylazanide Chemical compound [Li+].[Li+].C[Si](C)(C)[NH-].C[Si](C)(C)[NH-] SGDINNZGYDHHKM-UHFFFAOYSA-N 0.000 description 1
238000010790 dilution Methods 0.000 description 1
239000012895 dilution Substances 0.000 description 1
XEYBRNLFEZDVAW-ARSRFYASSA-N dinoprostone Chemical compound CCCCC[C@H](O)\C=C\[C@H]1[C@H](O)CC(=O)[C@@H]1C\C=C/CCCC(O)=O XEYBRNLFEZDVAW-ARSRFYASSA-N 0.000 description 1
229960002986 dinoprostone Drugs 0.000 description 1
238000010494 dissociation reaction Methods 0.000 description 1
230000005593 dissociations Effects 0.000 description 1
238000009826 distribution Methods 0.000 description 1
125000005678 ethenylene group Chemical class [H]C([*:1])=C([H])[*:2] 0.000 description 1
150000002170 ethers Chemical class 0.000 description 1
HHFAWKCIHAUFRX-UHFFFAOYSA-N ethoxide Chemical compound CC[O-] HHFAWKCIHAUFRX-UHFFFAOYSA-N 0.000 description 1
FCZCIXQGZOUIDN-UHFFFAOYSA-N ethyl 2-diethoxyphosphinothioyloxyacetate Chemical compound CCOC(=O)COP(=S)(OCC)OCC FCZCIXQGZOUIDN-UHFFFAOYSA-N 0.000 description 1
PSOZUQKKUGXCEN-UHFFFAOYSA-N ethyl 3,4-dihydro-2h-chromene-2-carboxylate Chemical compound C1=CC=C2OC(C(=O)OCC)CCC2=C1 PSOZUQKKUGXCEN-UHFFFAOYSA-N 0.000 description 1
SVHOXRFBCFZGAD-UHFFFAOYSA-N ethyl 4-hydroxy-3-prop-2-enylbenzoate Chemical compound CCOC(=O)C1=CC=C(O)C(CC=C)=C1 SVHOXRFBCFZGAD-UHFFFAOYSA-N 0.000 description 1
CJVFJZNWXDFXHF-UHFFFAOYSA-N ethyl 4-oxochromene-2-carboxylate Chemical compound C1=CC=C2OC(C(=O)OCC)=CC(=O)C2=C1 CJVFJZNWXDFXHF-UHFFFAOYSA-N 0.000 description 1
DXHQVNGGHNWZEF-UHFFFAOYSA-N ethyl 7-chloro-2-(3-phenylpropyl)-2,3-dihydro-1-benzofuran-5-carboxylate Chemical compound O1C=2C(Cl)=CC(C(=O)OCC)=CC=2CC1CCCC1=CC=CC=C1 DXHQVNGGHNWZEF-UHFFFAOYSA-N 0.000 description 1
LBYAHPDCNXILBM-UHFFFAOYSA-N ethyl 7-chloro-2-(hydroxymethyl)-2,3-dihydro-1-benzofuran-5-carboxylate Chemical compound ClC1=CC(C(=O)OCC)=CC2=C1OC(CO)C2 LBYAHPDCNXILBM-UHFFFAOYSA-N 0.000 description 1
VBOTZRKRCVBLNR-UHFFFAOYSA-N ethyl 7-chloro-2-(trifluoromethylsulfonyloxymethyl)-2,3-dihydro-1-benzofuran-5-carboxylate Chemical compound ClC1=CC(C(=O)OCC)=CC2=C1OC(COS(=O)(=O)C(F)(F)F)C2 VBOTZRKRCVBLNR-UHFFFAOYSA-N 0.000 description 1
RJHHEKZNYOSXOX-NTEUORMPSA-N ethyl 8-[(e)-2-[4-[4-(4-fluorophenyl)butoxy]phenyl]ethenyl]-4-oxochromene-2-carboxylate Chemical compound C=12OC(C(=O)OCC)=CC(=O)C2=CC=CC=1\C=C\C(C=C1)=CC=C1OCCCCC1=CC=C(F)C=C1 RJHHEKZNYOSXOX-NTEUORMPSA-N 0.000 description 1
GECOLABOBGRIGY-UHFFFAOYSA-N ethyl 8-nitro-4-oxochromene-2-carboxylate Chemical compound C1=CC([N+]([O-])=O)=C2OC(C(=O)OCC)=CC(=O)C2=C1 GECOLABOBGRIGY-UHFFFAOYSA-N 0.000 description 1
125000000816 ethylene group Chemical group [H]C([H])([*:1])C([H])([H])[*:2] 0.000 description 1
238000000605 extraction 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
150000004665 fatty acids Chemical class 0.000 description 1
125000001207 fluorophenyl group Chemical group 0.000 description 1
125000000524 functional group Chemical group 0.000 description 1
239000007789 gas Substances 0.000 description 1
239000012362 glacial acetic acid Substances 0.000 description 1
210000005003 heart tissue Anatomy 0.000 description 1
239000012456 homogeneous solution Substances 0.000 description 1
125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
238000007327 hydrogenolysis reaction Methods 0.000 description 1
XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
125000004356 hydroxy functional group Chemical group O* 0.000 description 1
125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
239000005457 ice water Substances 0.000 description 1
238000011534 incubation Methods 0.000 description 1
IENZCGNHSIMFJE-UHFFFAOYSA-N indole-5-carboxylic acid Chemical compound OC(=O)C1=CC=C2NC=CC2=C1 IENZCGNHSIMFJE-UHFFFAOYSA-N 0.000 description 1
230000008595 infiltration Effects 0.000 description 1
238000001764 infiltration Methods 0.000 description 1
230000004968 inflammatory condition Effects 0.000 description 1
230000002401 inhibitory effect Effects 0.000 description 1
238000006713 insertion reaction Methods 0.000 description 1
229910052740 iodine Inorganic materials 0.000 description 1
239000011630 iodine Substances 0.000 description 1
INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
230000000302 ischemic effect Effects 0.000 description 1
150000002576 ketones Chemical class 0.000 description 1
CFHGBZLNZZVTAY-UHFFFAOYSA-N lawesson's reagent Chemical compound C1=CC(OC)=CC=C1P1(=S)SP(=S)(C=2C=CC(OC)=CC=2)S1 CFHGBZLNZZVTAY-UHFFFAOYSA-N 0.000 description 1
210000000265 leukocyte Anatomy 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
239000003446 ligand Substances 0.000 description 1
235000019421 lipase Nutrition 0.000 description 1
150000002632 lipids Chemical class 0.000 description 1
239000007788 liquid Substances 0.000 description 1
230000002132 lysosomal effect Effects 0.000 description 1
NXPHGHWWQRMDIA-UHFFFAOYSA-M magnesium;carbanide;bromide Chemical compound [CH3-].[Mg+2].[Br-] NXPHGHWWQRMDIA-UHFFFAOYSA-M 0.000 description 1
230000002503 metabolic effect Effects 0.000 description 1
229910052751 metal Inorganic materials 0.000 description 1
239000002184 metal Substances 0.000 description 1
VNWKTOKETHGBQD-UHFFFAOYSA-N methane Natural products C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 1
GBMDVOWEEQVZKZ-UHFFFAOYSA-N methanol;hydrate Chemical compound O.OC GBMDVOWEEQVZKZ-UHFFFAOYSA-N 0.000 description 1
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
DRYBMFJLYYEOBZ-UHFFFAOYSA-N methyl 1h-indole-5-carboxylate Chemical compound COC(=O)C1=CC=C2NC=CC2=C1 DRYBMFJLYYEOBZ-UHFFFAOYSA-N 0.000 description 1
BPMLMDIQXMAUAE-UHFFFAOYSA-N methyl 2-fluoro-4-(4-phenylbutoxy)benzoate Chemical compound C1=C(F)C(C(=O)OC)=CC=C1OCCCCC1=CC=CC=C1 BPMLMDIQXMAUAE-UHFFFAOYSA-N 0.000 description 1
ZSBIMTDWIGWJPW-UHFFFAOYSA-N methyl 3-chloro-4-hydroxybenzoate Chemical compound COC(=O)C1=CC=C(O)C(Cl)=C1 ZSBIMTDWIGWJPW-UHFFFAOYSA-N 0.000 description 1
229940050176 methyl chloride Drugs 0.000 description 1
235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
AZFQCTBZOPUVOW-UHFFFAOYSA-N methyl(triphenyl)phosphanium Chemical class C=1C=CC=CC=1[P+](C=1C=CC=CC=1)(C)C1=CC=CC=C1 AZFQCTBZOPUVOW-UHFFFAOYSA-N 0.000 description 1
LSEFCHWGJNHZNT-UHFFFAOYSA-M methyl(triphenyl)phosphanium;bromide Chemical compound [Br-].C=1C=CC=CC=1[P+](C=1C=CC=CC=1)(C)C1=CC=CC=C1 LSEFCHWGJNHZNT-UHFFFAOYSA-M 0.000 description 1
230000011987 methylation Effects 0.000 description 1
238000007069 methylation reaction Methods 0.000 description 1
SAWKFRBJGLMMES-UHFFFAOYSA-N methylphosphine Chemical class PC SAWKFRBJGLMMES-UHFFFAOYSA-N 0.000 description 1
125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 1
230000003843 mucus production Effects 0.000 description 1
HTYPVCKCDGTXGB-UHFFFAOYSA-N n-(3-acetyl-2-hydroxyphenyl)-2-(3-phenylpropyl)-2,3-dihydro-1-benzofuran-5-carboxamide Chemical compound CC(=O)C1=CC=CC(NC(=O)C=2C=C3CC(CCCC=4C=CC=CC=4)OC3=CC=2)=C1O HTYPVCKCDGTXGB-UHFFFAOYSA-N 0.000 description 1
NCDDJSJLKLHIIU-UHFFFAOYSA-N n-(3-acetyl-2-hydroxyphenyl)-2-(3-phenylpropyl)-3,4-dihydro-2h-chromene-6-carboxamide Chemical compound CC(=O)C1=CC=CC(NC(=O)C=2C=C3CCC(CCCC=4C=CC=CC=4)OC3=CC=2)=C1O NCDDJSJLKLHIIU-UHFFFAOYSA-N 0.000 description 1
GZGBWROZWUSXKG-UHFFFAOYSA-N n-(3-acetyl-2-hydroxyphenyl)-2-[(4-fluorophenyl)methoxymethyl]-2,3-dihydro-1-benzofuran-5-carboxamide Chemical compound CC(=O)C1=CC=CC(NC(=O)C=2C=C3CC(COCC=4C=CC(F)=CC=4)OC3=CC=2)=C1O GZGBWROZWUSXKG-UHFFFAOYSA-N 0.000 description 1
YXXUCHQPCFWZNE-UHFFFAOYSA-N n-(3-acetyl-2-hydroxyphenyl)-4-chloro-2-(3-phenylpropyl)-2,3-dihydro-1-benzofuran-5-carboxamide Chemical compound CC(=O)C1=CC=CC(NC(=O)C=2C(=C3CC(CCCC=4C=CC=CC=4)OC3=CC=2)Cl)=C1O YXXUCHQPCFWZNE-UHFFFAOYSA-N 0.000 description 1
BCGGWSQCCFOJCN-UHFFFAOYSA-N n-(3-acetyl-2-hydroxyphenyl)-6-chloro-2-(3-phenylpropyl)-2,3-dihydro-1-benzofuran-5-carboxamide Chemical compound CC(=O)C1=CC=CC(NC(=O)C=2C(=CC=3OC(CCCC=4C=CC=CC=4)CC=3C=2)Cl)=C1O BCGGWSQCCFOJCN-UHFFFAOYSA-N 0.000 description 1
229910017604 nitric acid Inorganic materials 0.000 description 1
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
125000004433 nitrogen atom Chemical group N* 0.000 description 1
230000009871 nonspecific binding Effects 0.000 description 1
150000002901 organomagnesium compounds Chemical class 0.000 description 1
125000004430 oxygen atom Chemical group O* 0.000 description 1
229910052763 palladium Inorganic materials 0.000 description 1
FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 description 1
239000008194 pharmaceutical composition Substances 0.000 description 1
150000004714 phosphonium salts Chemical class 0.000 description 1
TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
230000002265 prevention Effects 0.000 description 1
150000003141 primary amines Chemical class 0.000 description 1
XEYBRNLFEZDVAW-UHFFFAOYSA-N prostaglandin E2 Natural products CCCCCC(O)C=CC1C(O)CC(=O)C1CC=CCCCC(O)=O XEYBRNLFEZDVAW-UHFFFAOYSA-N 0.000 description 1
AOJFQRQNPXYVLM-UHFFFAOYSA-N pyridin-1-ium;chloride Chemical compound [Cl-].C1=CC=[NH+]C=C1 AOJFQRQNPXYVLM-UHFFFAOYSA-N 0.000 description 1
150000003248 quinolines Chemical class 0.000 description 1
238000011160 research Methods 0.000 description 1
230000028327 secretion Effects 0.000 description 1
239000001632 sodium acetate Substances 0.000 description 1
235000017281 sodium acetate Nutrition 0.000 description 1
ODZPKZBBUMBTMG-UHFFFAOYSA-N sodium amide Chemical compound [NH2-].[Na+] ODZPKZBBUMBTMG-UHFFFAOYSA-N 0.000 description 1
AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 1
235000019345 sodium thiosulphate Nutrition 0.000 description 1
239000011343 solid material Substances 0.000 description 1
230000009870 specific binding Effects 0.000 description 1
230000004936 stimulating effect Effects 0.000 description 1
238000006467 substitution reaction Methods 0.000 description 1
150000003457 sulfones Chemical class 0.000 description 1
150000003462 sulfoxides Chemical class 0.000 description 1
235000020357 syrup Nutrition 0.000 description 1
239000006188 syrup Substances 0.000 description 1
239000003826 tablet Substances 0.000 description 1
108010063973 teneurin-1 Proteins 0.000 description 1
150000003536 tetrazoles Chemical class 0.000 description 1
125000001391 thioamide group Chemical group 0.000 description 1
150000003568 thioethers Chemical class 0.000 description 1
230000001732 thrombotic effect Effects 0.000 description 1
150000003595 thromboxanes Chemical class 0.000 description 1
238000000844 transformation Methods 0.000 description 1
125000002827 triflate group Chemical group FC(S(=O)(=O)O*)(F)F 0.000 description 1
LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
230000008728 vascular permeability Effects 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
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- A—HUMAN NECESSITIES
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
- A—HUMAN NECESSITIES
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P27/02—Ophthalmic agents
- A61P27/14—Decongestants or antiallergics
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/08—Antiallergic agents
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C205/00—Compounds containing nitro groups bound to a carbon skeleton
- C07C205/45—Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by at least one doubly—bound oxygen atom, not being part of a —CHO group
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/51—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by pyrolysis, rearrangement or decomposition
- C07C45/54—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by pyrolysis, rearrangement or decomposition of compounds containing doubly bound oxygen atoms, e.g. esters
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
- C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D311/04—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
- C07D311/22—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4
- C07D311/24—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4 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 in position 2
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/04—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups

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Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Life Sciences & Earth Sciences (AREA)
General Health & Medical Sciences (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Bioinformatics & Cheminformatics (AREA)
Pharmacology & Pharmacy (AREA)
Engineering & Computer Science (AREA)
Animal Behavior & Ethology (AREA)
Chemical Kinetics & Catalysis (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Pulmonology (AREA)
Immunology (AREA)
Rheumatology (AREA)
Dermatology (AREA)
Cardiology (AREA)
Heart & Thoracic Surgery (AREA)
Physical Education & Sports Medicine (AREA)
Urology & Nephrology (AREA)
Ophthalmology & Optometry (AREA)
Biomedical Technology (AREA)
Neurology (AREA)
Neurosurgery (AREA)
Orthopedic Medicine & Surgery (AREA)
Pain & Pain Management (AREA)
Vascular Medicine (AREA)
Otolaryngology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Plural Heterocyclic Compounds (AREA)
Pyrane Compounds (AREA)

NO19984330A 1996-03-21 1998-09-17 Benzopyranderivater som har leukotrien-antagonistisk virkning, fremgangsmate for fremstilling og anvendelse derav NO319612B1 (no)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
ES009600682A ES2127106B1 (es)	1996-03-21	1996-03-21	Derivados benzopiranicos con accion antagonista de los leucotrienos, procedimiento para su preparacion y utilizacion de los mismos.
PCT/EP1997/001418 WO1997034885A1 (en)	1996-03-21	1997-03-20	Benzopyran derivatives having leukotriene-antagonistic action

Publications (3)

Publication Number	Publication Date
NO984330D0 NO984330D0 (no)	1998-09-17
NO984330L NO984330L (no)	1998-10-09
NO319612B1 true NO319612B1 (no)	2005-08-29

Family

ID=8294261

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
NO19984330A NO319612B1 (no)	1996-03-21	1998-09-17	Benzopyranderivater som har leukotrien-antagonistisk virkning, fremgangsmate for fremstilling og anvendelse derav

Country Status (30)

Country	Link
US (1)	US5990142A (de)
EP (1)	EP0888327B1 (de)
JP (1)	JP3914575B2 (de)
KR (1)	KR100378892B1 (de)
CN (1)	CN1182129C (de)
AT (1)	ATE219073T1 (de)
AU (1)	AU707282B2 (de)
BG (1)	BG63433B1 (de)
BR (1)	BR9708215A (de)
CA (1)	CA2249402C (de)
CU (1)	CU22777A3 (de)
CZ (1)	CZ296260B6 (de)
DE (1)	DE69713300T2 (de)
DK (1)	DK0888327T3 (de)
EA (1)	EA001680B1 (de)
EE (1)	EE03526B1 (de)
ES (2)	ES2127106B1 (de)
GE (1)	GEP20012416B (de)
HU (1)	HUP9901326A3 (de)
IL (1)	IL126296A (de)
NO (1)	NO319612B1 (de)
NZ (1)	NZ331953A (de)
PL (1)	PL189562B1 (de)
PT (1)	PT888327E (de)
RS (1)	RS49588B (de)
SI (1)	SI0888327T1 (de)
SK (1)	SK282979B6 (de)
TR (1)	TR199801857T2 (de)
UA (1)	UA65535C2 (de)
WO (1)	WO1997034885A1 (de)

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JP4745577B2 (ja)	1999-11-24	2011-08-10	ザリサーチファウンデイションオブステイトユニバーシティーオブニューヨーク	アミノアシル化活性を有した触媒ＲＮＡｓ
WO2003070740A1 (en) *	2002-02-15	2003-08-28	The Research Foundation Of State University Of New York	RIBOZYMES WITH BROAD tRNA AMINOACYLATION ACTIVITY
EP1579010A4 (de) *	2002-10-17	2010-07-21	Decode Genetics Ehf	Myokardinfarkt-suszeptibilitätsgen;behandlungsverfahren
US7851486B2 (en)	2002-10-17	2010-12-14	Decode Genetics Ehf.	Susceptibility gene for myocardial infarction, stroke, and PAOD; methods of treatment
ITTO20030140U1 (it) *	2003-09-16	2005-03-17	Interfila Srl	Matita cosmetica
WO2005033092A1 (en)	2003-09-19	2005-04-14	Galileo Pharmaceuticals, Inc.	Chroman derivatives
CN100475781C (zh) *	2004-02-13	2009-04-08	沃尼尔·朗伯有限责任公司	雄激素受体调节剂
EA009902B1 (ru) *	2004-02-13	2008-04-28	УОРНЕР-ЛАМБЕРТ КОМПАНИ Эл-Эл-Си	Модуляторы рецепторов андрогенов
JP2007532621A (ja)	2004-04-13	2007-11-15	ワーナー−ランバートカンパニーリミテッドライアビリティーカンパニー	アンドロゲンモジュレータ
MXPA06015169A (es)	2004-07-08	2007-08-21	Warner Lambert Co	Moduladores de androgenos.
US20080064745A1 (en) *	2004-08-18	2008-03-13	Warner-Lambert Company Llc	Androgen Modulators
TW200724139A (en)	2005-05-05	2007-07-01	Warner Lambert Co	Androgen modulators
US20090170886A1 (en) *	2005-08-08	2009-07-02	Pfizer Inc	Androgen modulators
EP1964916B1 (de) *	2005-12-06	2012-08-01	The University of Tokyo	Mehrzweck-Acylierungskatalysator und Verwendung davon
ITMI20061606A1 (it) *	2006-08-09	2008-02-10	Dipharma Spa	Procedimento per la preparazione di composti nitrilici
CN102304052A (zh) *	2011-07-28	2012-01-04	浙江大学	一种制备5-溴-2-羟基-3-硝基苯乙酮的方法
CN103980257B (zh) *	2014-05-28	2016-04-27	苏州开元民生科技股份有限公司	8-硝基-2-四氮唑基-4-羰基苯并吡喃的合成方法
CN104402711A (zh) *	2014-11-12	2015-03-11	平湖优康药物研发有限公司	一种抗哮喘药物普伦斯特中间体的合成工艺
CN113651788B (zh) *	2021-09-16	2023-11-21	东华理工大学	一种3-胺烷基色酮化合物及其制备方法

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Publication number	Priority date	Publication date	Assignee	Title
US4977162A (en) *	1989-07-13	1990-12-11	Rorer Pharmaceutical Corporation	Quinolinyl-chromone derivatives and use for treatment of hypersensitive ailments
JPH0395144A (ja) *	1989-08-04	1991-04-19	Ono Pharmaceut Co Ltd	アミノフェノール誘導体の製造方法

1996
- 1996-03-21 ES ES009600682A patent/ES2127106B1/es not_active Expired - Lifetime
1997
- 1997-03-20 JP JP53315997A patent/JP3914575B2/ja not_active Expired - Fee Related
- 1997-03-20 NZ NZ331953A patent/NZ331953A/xx not_active IP Right Cessation
- 1997-03-20 DK DK97914280T patent/DK0888327T3/da active
- 1997-03-20 DE DE69713300T patent/DE69713300T2/de not_active Expired - Fee Related
- 1997-03-20 PL PL97329027A patent/PL189562B1/pl not_active IP Right Cessation
- 1997-03-20 EE EE9800318A patent/EE03526B1/xx not_active IP Right Cessation
- 1997-03-20 TR TR1998/01857T patent/TR199801857T2/xx unknown
- 1997-03-20 WO PCT/EP1997/001418 patent/WO1997034885A1/en not_active Ceased
- 1997-03-20 ES ES97914280T patent/ES2176719T3/es not_active Expired - Lifetime
- 1997-03-20 GE GEAP19974493A patent/GEP20012416B/en unknown
- 1997-03-20 BR BR9708215-5A patent/BR9708215A/pt not_active Application Discontinuation
- 1997-03-20 CA CA002249402A patent/CA2249402C/en not_active Expired - Fee Related
- 1997-03-20 EA EA199800738A patent/EA001680B1/ru unknown
- 1997-03-20 US US09/142,922 patent/US5990142A/en not_active Expired - Fee Related
- 1997-03-20 AU AU21587/97A patent/AU707282B2/en not_active Ceased
- 1997-03-20 UA UA98094930A patent/UA65535C2/uk unknown
- 1997-03-20 SI SI9730340T patent/SI0888327T1/xx unknown
- 1997-03-20 AT AT97914280T patent/ATE219073T1/de not_active IP Right Cessation
- 1997-03-20 IL IL12629697A patent/IL126296A/en not_active IP Right Cessation
- 1997-03-20 HU HU9901326A patent/HUP9901326A3/hu unknown
- 1997-03-20 CN CNB971931933A patent/CN1182129C/zh not_active Expired - Fee Related
- 1997-03-20 EP EP97914280A patent/EP0888327B1/de not_active Expired - Lifetime
- 1997-03-20 KR KR10-1998-0707399A patent/KR100378892B1/ko not_active Expired - Fee Related
- 1997-03-20 PT PT97914280T patent/PT888327E/pt unknown
- 1997-03-20 CZ CZ0299598A patent/CZ296260B6/cs not_active IP Right Cessation
- 1997-03-20 SK SK1272-98A patent/SK282979B6/sk not_active IP Right Cessation
1998
- 1998-09-17 NO NO19984330A patent/NO319612B1/no not_active IP Right Cessation
- 1998-09-17 BG BG102775A patent/BG63433B1/bg unknown
- 1998-09-18 RS YUP-407/98A patent/RS49588B/sr unknown
- 1998-09-18 CU CU1998130A patent/CU22777A3/es not_active IP Right Cessation

Also Published As

Publication number	Publication date
CA2249402C (en)	2006-10-24
AU707282B2 (en)	1999-07-08
BG63433B1 (bg)	2002-01-31
NZ331953A (en)	1999-03-29
SK127298A3 (en)	1999-03-12
CA2249402A1 (en)	1997-09-25
ATE219073T1 (de)	2002-06-15
KR20000064682A (ko)	2000-11-06
TR199801857T2 (xx)	1998-12-21
YU40798A (en)	1999-11-22
AU2158797A (en)	1997-10-10
JP3914575B2 (ja)	2007-05-16
WO1997034885A1 (en)	1997-09-25
HUP9901326A3 (en)	2000-12-28
EP0888327B1 (de)	2002-06-12
RS49588B (sr)	2007-06-04
HUP9901326A2 (hu)	1999-08-30
NO984330D0 (no)	1998-09-17
HK1018701A1 (en)	1999-12-30
PL329027A1 (en)	1999-03-01
UA65535C2 (en)	2004-04-15
EE03526B1 (et)	2001-10-15
US5990142A (en)	1999-11-23
EA001680B1 (ru)	2001-06-25
CU22777A3 (es)	2002-07-24
EA199800738A1 (ru)	1999-06-24
DE69713300D1 (de)	2002-07-18
IL126296A0 (en)	1999-05-09
ES2127106A1 (es)	1999-04-01
ES2127106B1 (es)	1999-11-16
GEP20012416B (en)	2001-04-25
DK0888327T3 (da)	2002-09-16
CZ299598A3 (cs)	1999-03-17
PT888327E (pt)	2002-11-29
CN1214048A (zh)	1999-04-14
SI0888327T1 (en)	2002-10-31
NO984330L (no)	1998-10-09
SK282979B6 (sk)	2003-01-09
CN1182129C (zh)	2004-12-29
EP0888327A1 (de)	1999-01-07
ES2176719T3 (es)	2002-12-01
BR9708215A (pt)	2000-01-04
BG102775A (en)	1999-08-31
CZ296260B6 (cs)	2006-02-15
DE69713300T2 (de)	2002-09-26
PL189562B1 (pl)	2005-08-31
JP2000506878A (ja)	2000-06-06
KR100378892B1 (ko)	2005-11-14
IL126296A (en)	2002-08-14
EE9800318A (et)	1999-04-15

Legal Events

Date	Code	Title	Description
2011-10-24	MM1K	Lapsed by not paying the annual fees

Publication	Publication Date	Title
EP0888327B1 (de)	2002-06-12	Benzopyran derivate mit leukotrien-antagonistischer wirkung
US4474788A (en)	1984-10-02	Anti-SRSA quinoline carboxylic acid derivatives
AU728329B2 (en)	2001-01-04	New substituted biphenyl or phenylpyridine compounds, a process for their preparation and pharmaceutical compositions containing them
US5348962A (en)	1994-09-20	Hydroxyquinolone derivatives compounds which have pharmaceutical utility
EP0233763B1 (de)	1991-01-30	2-Substituierte Chinolindicarbonsäure
IE44879B1 (en)	1982-05-05	N-heterocyclyl-4-hydroxy-quinoline-3-carboxamides
US4851409A (en)	1989-07-25	2-substituted quinoline dioic acids and pharmaceutical compositions
JPH0653736B2 (ja)	1994-07-20	新規な酸性インド−ル化合物
WO1996006822A1 (en)	1996-03-07	Ortho-substituted aromatic ether compounds and their use in pharmaceutical compositions for pain relief
DE3834204A1 (de)	1989-04-20	4h-1-benzopyran-4-on-derivate oder deren salze, verfahren zur herstellung derselben und pharmazeutische mittel mit einem gehalt derselben als wirkstoff
US5175173A (en)	1992-12-29	Carboxamides useful as antiemetic or antipsychotic agents
CA1298838C (en)	1992-04-14	2-substituted quinolines
AU761327B2 (en)	2003-06-05	Fused benzene heterocycle derivatives and utilization thereof
JP2939280B2 (ja)	1999-08-25	フッ素置換メトキシキノロンカルボン酸誘導体
US5597833A (en)	1997-01-28	Substituted quinol-2-yl-methoxy-phenylacetic acid derivatives
KR100497896B1 (ko)	2005-12-12	플라본유도체및이를함유하는의약
JPH07103105B2 (ja)	1995-11-08	インドール誘導体及びその製造方法
US5246966A (en)	1993-09-21	Substituted alkenoic acid and its derivatives
US5428171A (en)	1995-06-27	2-substituted quinoline dioic acids
JPH0250906B2 (de)	1990-11-05
IE43737B1 (en)	1981-05-20	3-hydroxymethylene-6,7-dimethoxy-2-methyl-4-oxo-1,2,3,4-tetrahydro-1-quinoline carboxylic acid esters
SI9300202A (sl)	1994-12-31	Derivati hidroksikinolona
JPWO2000007992A1 (ja)	2001-10-09	ベンゼン縮合ヘテロ環誘導体及びその用途