CA1210770A - Leukotriene antagonists - Google Patents
Leukotriene antagonistsInfo
- Publication number
- CA1210770A CA1210770A CA000437216A CA437216A CA1210770A CA 1210770 A CA1210770 A CA 1210770A CA 000437216 A CA000437216 A CA 000437216A CA 437216 A CA437216 A CA 437216A CA 1210770 A CA1210770 A CA 1210770A
- Authority
- CA
- Canada
- Prior art keywords
- hydroxy
- gamma
- carbon atoms
- beta
- alkyl
- Prior art date
- Legal status (The legal status 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 status listed.)
- Expired
Links
- 239000003199 leukotriene receptor blocking agent Substances 0.000 title abstract description 4
- 150000001875 compounds Chemical class 0.000 claims abstract description 273
- 239000000126 substance Substances 0.000 claims abstract description 13
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 90
- 238000000034 method Methods 0.000 claims description 84
- 125000004432 carbon atom Chemical group C* 0.000 claims description 69
- 125000000217 alkyl group Chemical group 0.000 claims description 46
- -1 monocyclic heterocyclic radical Chemical class 0.000 claims description 46
- 239000002253 acid Substances 0.000 claims description 41
- KWOLFJPFCHCOCG-UHFFFAOYSA-N Acetophenone Chemical compound CC(=O)C1=CC=CC=C1 KWOLFJPFCHCOCG-UHFFFAOYSA-N 0.000 claims description 40
- 239000000047 product Substances 0.000 claims description 24
- 125000003545 alkoxy group Chemical group 0.000 claims description 15
- 238000010992 reflux Methods 0.000 claims description 14
- 229910052760 oxygen Inorganic materials 0.000 claims description 13
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 12
- 229910052717 sulfur Inorganic materials 0.000 claims description 12
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 11
- 238000007127 saponification reaction Methods 0.000 claims description 11
- 229910052736 halogen Inorganic materials 0.000 claims description 10
- 150000002367 halogens Chemical class 0.000 claims description 10
- 125000003342 alkenyl group Chemical group 0.000 claims description 9
- QGGRBWUQXAFYEC-UHFFFAOYSA-N 1-(2,4-dihydroxy-3-propylphenyl)ethanone Chemical compound CCCC1=C(O)C=CC(C(C)=O)=C1O QGGRBWUQXAFYEC-UHFFFAOYSA-N 0.000 claims description 7
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 7
- 239000001301 oxygen Substances 0.000 claims description 7
- 125000005842 heteroatom Chemical group 0.000 claims description 6
- 150000003839 salts Chemical class 0.000 claims description 6
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 5
- 125000000457 gamma-lactone group Chemical group 0.000 claims description 5
- NXDRSDPPZCVYBX-UHFFFAOYSA-N methyl 4-oxo-4-(4-sulfanylphenyl)butanoate Chemical compound COC(=O)CCC(=O)C1=CC=C(S)C=C1 NXDRSDPPZCVYBX-UHFFFAOYSA-N 0.000 claims description 5
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 5
- 150000003457 sulfones Chemical group 0.000 claims description 5
- 150000003462 sulfoxides Chemical group 0.000 claims description 5
- 239000011593 sulfur Chemical group 0.000 claims description 5
- 229910052739 hydrogen Inorganic materials 0.000 claims description 4
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 4
- 125000000896 monocarboxylic acid group Chemical group 0.000 claims description 4
- 159000000000 sodium salts Chemical class 0.000 claims description 4
- 125000000446 sulfanediyl group Chemical group *S* 0.000 claims description 4
- 150000003536 tetrazoles Chemical class 0.000 claims description 4
- 238000011282 treatment Methods 0.000 claims description 4
- AMUGZLWRHPCZJU-UHFFFAOYSA-N 4-[4-[3-(4-acetyl-3-hydroxy-2-propylphenoxy)propylsulfanyl]phenyl]-4-oxobutanoic acid Chemical compound CCCC1=C(O)C(C(C)=O)=CC=C1OCCCSC1=CC=C(C(=O)CCC(O)=O)C=C1 AMUGZLWRHPCZJU-UHFFFAOYSA-N 0.000 claims description 3
- 239000004215 Carbon black (E152) Substances 0.000 claims description 3
- 125000002015 acyclic group Chemical group 0.000 claims description 3
- 125000002252 acyl group Chemical group 0.000 claims description 3
- 125000004429 atom Chemical group 0.000 claims description 3
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 3
- RXKJFZQQPQGTFL-UHFFFAOYSA-N dihydroxyacetone Chemical compound OCC(=O)CO RXKJFZQQPQGTFL-UHFFFAOYSA-N 0.000 claims description 3
- 125000001188 haloalkyl group Chemical group 0.000 claims description 3
- 229930195733 hydrocarbon Natural products 0.000 claims description 3
- 239000001257 hydrogen Substances 0.000 claims description 3
- CBOIHMRHGLHBPB-UHFFFAOYSA-N hydroxymethyl Chemical compound O[CH2] CBOIHMRHGLHBPB-UHFFFAOYSA-N 0.000 claims description 3
- 125000000468 ketone group Chemical group 0.000 claims description 3
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 3
- 150000003254 radicals Chemical class 0.000 claims description 3
- 125000004001 thioalkyl group Chemical group 0.000 claims description 3
- 125000005034 trifluormethylthio group Chemical group FC(S*)(F)F 0.000 claims description 3
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 3
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 2
- 230000000875 corresponding effect Effects 0.000 claims 7
- ZAKKEARLDPTRLX-UHFFFAOYSA-N 4-[4-[3-(4-acetyl-3-hydroxy-2-propylphenoxy)propylsulfonyl]phenyl]-4-oxobutanoic acid Chemical compound CCCC1=C(O)C(C(C)=O)=CC=C1OCCCS(=O)(=O)C1=CC=C(C(=O)CCC(O)=O)C=C1 ZAKKEARLDPTRLX-UHFFFAOYSA-N 0.000 claims 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims 2
- 239000012442 inert solvent Substances 0.000 claims 2
- 150000001451 organic peroxides Chemical class 0.000 claims 2
- KEWWHJFWHZEDDE-UHFFFAOYSA-M sodium;4-[4-[3-(4-acetyl-3-hydroxy-2-propylphenoxy)propoxy]phenyl]-4-hydroxy-3-methylbutanoate Chemical compound [Na+].CCCC1=C(O)C(C(C)=O)=CC=C1OCCCOC1=CC=C(C(O)C(C)CC([O-])=O)C=C1 KEWWHJFWHZEDDE-UHFFFAOYSA-M 0.000 claims 2
- HYMFDMFIXDCBBD-UHFFFAOYSA-M sodium;4-[4-[3-(4-acetyl-3-hydroxy-2-propylphenoxy)propylsulfanyl]phenyl]-4-hydroxy-3-methylbutanoate Chemical compound [Na+].CCCC1=C(O)C(C(C)=O)=CC=C1OCCCSC1=CC=C(C(O)C(C)CC([O-])=O)C=C1 HYMFDMFIXDCBBD-UHFFFAOYSA-M 0.000 claims 2
- 239000007858 starting material Substances 0.000 claims 2
- 239000007859 condensation product Substances 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- 125000002950 monocyclic group Chemical group 0.000 claims 1
- 150000002617 leukotrienes Chemical class 0.000 abstract description 14
- 239000005557 antagonist Substances 0.000 abstract description 2
- 206010002198 Anaphylactic reaction Diseases 0.000 abstract 1
- 230000036783 anaphylactic response Effects 0.000 abstract 1
- 208000003455 anaphylaxis Diseases 0.000 abstract 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 123
- 239000000203 mixture Substances 0.000 description 114
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 87
- 238000002360 preparation method Methods 0.000 description 85
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 80
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 66
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 66
- 239000000243 solution Substances 0.000 description 64
- 238000004458 analytical method Methods 0.000 description 60
- 239000011541 reaction mixture Substances 0.000 description 52
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 43
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 40
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 35
- VLKZOEOYAKHREP-UHFFFAOYSA-N hexane Substances CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 35
- 150000002148 esters Chemical class 0.000 description 33
- 239000000741 silica gel Substances 0.000 description 33
- 229910002027 silica gel Inorganic materials 0.000 description 33
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 32
- 239000012267 brine Substances 0.000 description 31
- 238000004587 chromatography analysis Methods 0.000 description 31
- 235000019439 ethyl acetate Nutrition 0.000 description 28
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 27
- 239000011734 sodium Substances 0.000 description 27
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 26
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 26
- 229910052708 sodium Inorganic materials 0.000 description 26
- 239000007832 Na2SO4 Substances 0.000 description 25
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 25
- 229910052938 sodium sulfate Inorganic materials 0.000 description 25
- 235000011152 sodium sulphate Nutrition 0.000 description 25
- 150000004702 methyl esters Chemical class 0.000 description 24
- 238000005481 NMR spectroscopy Methods 0.000 description 23
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 23
- 150000002596 lactones Chemical class 0.000 description 22
- 239000007787 solid Substances 0.000 description 22
- 101150041968 CDC13 gene Proteins 0.000 description 21
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 21
- 239000000284 extract Substances 0.000 description 20
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 18
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 16
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 16
- 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 15
- 238000006243 chemical reaction Methods 0.000 description 15
- 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 15
- 239000012044 organic layer Substances 0.000 description 13
- 229910000027 potassium carbonate Inorganic materials 0.000 description 13
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 12
- 239000004480 active ingredient Substances 0.000 description 11
- 239000000725 suspension Substances 0.000 description 11
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 10
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 9
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 9
- 239000006260 foam Substances 0.000 description 9
- 238000004128 high performance liquid chromatography Methods 0.000 description 9
- 238000003756 stirring Methods 0.000 description 9
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 8
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 8
- RDOXTESZEPMUJZ-UHFFFAOYSA-N anisole Chemical compound COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 description 8
- 238000001704 evaporation Methods 0.000 description 8
- 230000008020 evaporation Effects 0.000 description 8
- 239000010410 layer Substances 0.000 description 8
- 239000012299 nitrogen atmosphere Substances 0.000 description 7
- 235000011181 potassium carbonates Nutrition 0.000 description 7
- 229910000033 sodium borohydride Inorganic materials 0.000 description 7
- 239000012279 sodium borohydride Substances 0.000 description 7
- 239000002904 solvent Substances 0.000 description 7
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 6
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- 241001465754 Metazoa Species 0.000 description 6
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 6
- AXCZMVOFGPJBDE-UHFFFAOYSA-L calcium dihydroxide Chemical compound [OH-].[OH-].[Ca+2] AXCZMVOFGPJBDE-UHFFFAOYSA-L 0.000 description 6
- 239000000920 calcium hydroxide Substances 0.000 description 6
- 229910001861 calcium hydroxide Inorganic materials 0.000 description 6
- 235000011116 calcium hydroxide Nutrition 0.000 description 6
- 239000008194 pharmaceutical composition Substances 0.000 description 6
- 235000015320 potassium carbonate Nutrition 0.000 description 6
- 238000000746 purification Methods 0.000 description 6
- 239000011347 resin Substances 0.000 description 6
- 229920005989 resin Polymers 0.000 description 6
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 5
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- 239000000706 filtrate Substances 0.000 description 5
- 238000001914 filtration Methods 0.000 description 5
- 239000007788 liquid Substances 0.000 description 5
- 239000000843 powder Substances 0.000 description 5
- 125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 5
- 229940014800 succinic anhydride Drugs 0.000 description 5
- JIXDOBAQOWOUPA-UHFFFAOYSA-N 1-fluoro-2-methoxybenzene Chemical compound COC1=CC=CC=C1F JIXDOBAQOWOUPA-UHFFFAOYSA-N 0.000 description 4
- FALRKNHUBBKYCC-UHFFFAOYSA-N 2-(chloromethyl)pyridine-3-carbonitrile Chemical compound ClCC1=NC=CC=C1C#N FALRKNHUBBKYCC-UHFFFAOYSA-N 0.000 description 4
- YXHKONLOYHBTNS-UHFFFAOYSA-N Diazomethane Chemical compound C=[N+]=[N-] YXHKONLOYHBTNS-UHFFFAOYSA-N 0.000 description 4
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 4
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- 231100000673 dose–response relationship Toxicity 0.000 description 4
- 230000005764 inhibitory process Effects 0.000 description 4
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 4
- ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 4
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 4
- 235000019341 magnesium sulphate Nutrition 0.000 description 4
- UZKWTJUDCOPSNM-UHFFFAOYSA-N methoxybenzene Substances CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 description 4
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 description 4
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 4
- 150000002825 nitriles Chemical class 0.000 description 4
- 239000000651 prodrug Substances 0.000 description 4
- 229940002612 prodrug Drugs 0.000 description 4
- 235000017557 sodium bicarbonate Nutrition 0.000 description 4
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 4
- 239000011780 sodium chloride Substances 0.000 description 4
- 239000003826 tablet Substances 0.000 description 4
- QAEDZJGFFMLHHQ-UHFFFAOYSA-N trifluoroacetic anhydride Chemical compound FC(F)(F)C(=O)OC(=O)C(F)(F)F QAEDZJGFFMLHHQ-UHFFFAOYSA-N 0.000 description 4
- HFEASCCDHUVYKU-UHFFFAOYSA-N 1,2-dichloro-3-methoxybenzene Chemical group COC1=CC=CC(Cl)=C1Cl HFEASCCDHUVYKU-UHFFFAOYSA-N 0.000 description 3
- VEFLKXRACNJHOV-UHFFFAOYSA-N 1,3-dibromopropane Chemical compound BrCCCBr VEFLKXRACNJHOV-UHFFFAOYSA-N 0.000 description 3
- PPKAIMDMNWBOKN-UHFFFAOYSA-N 2-Oxo-4-phenylbutyric acid Chemical compound OC(=O)C(=O)CCC1=CC=CC=C1 PPKAIMDMNWBOKN-UHFFFAOYSA-N 0.000 description 3
- HFHFGHLXUCOHLN-UHFFFAOYSA-N 2-fluorophenol Chemical compound OC1=CC=CC=C1F HFHFGHLXUCOHLN-UHFFFAOYSA-N 0.000 description 3
- YOETUEMZNOLGDB-UHFFFAOYSA-N 2-methylpropyl carbonochloridate Chemical compound CC(C)COC(Cl)=O YOETUEMZNOLGDB-UHFFFAOYSA-N 0.000 description 3
- XJFZOSUFGSANIF-UHFFFAOYSA-N 3-chloro-2-(chloromethyl)prop-1-ene Chemical compound ClCC(=C)CCl XJFZOSUFGSANIF-UHFFFAOYSA-N 0.000 description 3
- OMTDIBZSUZNVJK-UHFFFAOYSA-N 4-(4-methoxyphenyl)-4-oxobutanoic acid Chemical compound COC1=CC=C(C(=O)CCC(O)=O)C=C1 OMTDIBZSUZNVJK-UHFFFAOYSA-N 0.000 description 3
- AWSADCRNHSUEMT-UHFFFAOYSA-N 4-[4-[3-(4-acetyl-3-hydroxy-2-propylphenoxy)propoxy]phenyl]-4-hydroxy-3,3-dimethylbutanoic acid Chemical compound C1=CC(C(C)=O)=C(O)C(CCC)=C1OCCCOC1=CC=C(C(O)C(C)(C)CC(O)=O)C=C1 AWSADCRNHSUEMT-UHFFFAOYSA-N 0.000 description 3
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- 241000700198 Cavia Species 0.000 description 3
- 241000700199 Cavia porcellus Species 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- ZTHYODDOHIVTJV-UHFFFAOYSA-N Propyl gallate Chemical compound CCCOC(=O)C1=CC(O)=C(O)C(O)=C1 ZTHYODDOHIVTJV-UHFFFAOYSA-N 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 239000008346 aqueous phase Substances 0.000 description 3
- 230000037396 body weight Effects 0.000 description 3
- UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 3
- 238000010438 heat treatment Methods 0.000 description 3
- 239000005457 ice water Substances 0.000 description 3
- 239000004615 ingredient Substances 0.000 description 3
- 239000003112 inhibitor Substances 0.000 description 3
- 150000002500 ions Chemical class 0.000 description 3
- 238000001819 mass spectrum Methods 0.000 description 3
- MYWUZJCMWCOHBA-VIFPVBQESA-N methamphetamine Chemical compound CN[C@@H](C)CC1=CC=CC=C1 MYWUZJCMWCOHBA-VIFPVBQESA-N 0.000 description 3
- ZVWCLYJTJQFOEZ-UHFFFAOYSA-N methyl 4-(3-fluoro-4-hydroxyphenyl)-4-oxobutanoate Chemical compound COC(=O)CCC(=O)C1=CC=C(O)C(F)=C1 ZVWCLYJTJQFOEZ-UHFFFAOYSA-N 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- LDMFITQBHOPZHQ-UHFFFAOYSA-N 1-[4-[3-(4-acetyl-3-hydroxy-2-propylphenoxy)propylsulfanyl]phenyl]-4-hydroxybutan-1-one Chemical compound CCCC1=C(O)C(C(C)=O)=CC=C1OCCCSC1=CC=C(C(=O)CCCO)C=C1 LDMFITQBHOPZHQ-UHFFFAOYSA-N 0.000 description 2
- SULYEHHGGXARJS-UHFFFAOYSA-N 2',4'-dihydroxyacetophenone Chemical class CC(=O)C1=CC=C(O)C=C1O SULYEHHGGXARJS-UHFFFAOYSA-N 0.000 description 2
- DTFKRVXLBCAIOZ-UHFFFAOYSA-N 2-methylanisole Chemical group COC1=CC=CC=C1C DTFKRVXLBCAIOZ-UHFFFAOYSA-N 0.000 description 2
- JGMLVCAXEIUFBW-UHFFFAOYSA-N 4-(2-methoxy-4-sulfanylphenyl)-4-oxobutanoic acid Chemical compound COC1=CC(S)=CC=C1C(=O)CCC(O)=O JGMLVCAXEIUFBW-UHFFFAOYSA-N 0.000 description 2
- KODRIPJJUNOTOQ-UHFFFAOYSA-N 4-(3-fluoro-2-hydroxyphenyl)-4-oxobutanoic acid Chemical compound OC(=O)CCC(=O)C1=CC=CC(F)=C1O KODRIPJJUNOTOQ-UHFFFAOYSA-N 0.000 description 2
- QKDLXQWEBIYZSS-UHFFFAOYSA-N 4-(4-hydroxyphenyl)-4-oxobutanoic acid Chemical compound OC(=O)CCC(=O)C1=CC=C(O)C=C1 QKDLXQWEBIYZSS-UHFFFAOYSA-N 0.000 description 2
- YNHQJUJPBNEXHQ-UHFFFAOYSA-N 4-[4-[3-(4-acetyl-3-hydroxy-2-propylphenoxy)propylsulfanyl]phenyl]-4-hydroxy-3-methylbutanoic acid Chemical compound C1=CC(C(C)=O)=C(O)C(CCC)=C1OCCCSC1=CC=C(C(O)C(C)CC(O)=O)C=C1 YNHQJUJPBNEXHQ-UHFFFAOYSA-N 0.000 description 2
- AKHAMPCKINXCDB-UHFFFAOYSA-N 4-[4-[3-(4-acetyl-3-hydroxy-2-propylphenoxy)propylsulfonyl]phenyl]-4-hydroxy-3-methylbutanoic acid Chemical compound C1=CC(C(C)=O)=C(O)C(CCC)=C1OCCCS(=O)(=O)C1=CC=C(C(O)C(C)CC(O)=O)C=C1 AKHAMPCKINXCDB-UHFFFAOYSA-N 0.000 description 2
- OFJAABUKTKNXTI-UHFFFAOYSA-N 4-[4-[3-(4-acetyl-3-hydroxy-2-propylphenyl)sulfanylpropoxy]-3-fluorophenyl]-4-oxobutanoic acid Chemical compound CCCC1=C(O)C(C(C)=O)=CC=C1SCCCOC1=CC=C(C(=O)CCC(O)=O)C=C1F OFJAABUKTKNXTI-UHFFFAOYSA-N 0.000 description 2
- NRJOGXQAYPTPJI-UHFFFAOYSA-N 4-oxo-4-(4-sulfanylphenyl)butanoic acid Chemical compound OC(=O)CCC(=O)C1=CC=C(S)C=C1 NRJOGXQAYPTPJI-UHFFFAOYSA-N 0.000 description 2
- WWOOCKNQNKQSAI-UHFFFAOYSA-N 5-[4-[3-(4-acetyl-3-hydroxy-2-propylphenoxy)propylsulfanyl]-3-fluorophenyl]-4-methyloxolan-2-one Chemical compound CCCC1=C(O)C(C(C)=O)=CC=C1OCCCSC1=CC=C(C2C(CC(=O)O2)C)C=C1F WWOOCKNQNKQSAI-UHFFFAOYSA-N 0.000 description 2
- 241000428352 Amma Species 0.000 description 2
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 206010006482 Bronchospasm Diseases 0.000 description 2
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical compound CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 2
- NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 description 2
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
- QQONPFPTGQHPMA-UHFFFAOYSA-N Propene Chemical compound CC=C QQONPFPTGQHPMA-UHFFFAOYSA-N 0.000 description 2
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
- KQNKJJBFUFKYFX-UHFFFAOYSA-N acetic acid;trihydrate Chemical compound O.O.O.CC(O)=O KQNKJJBFUFKYFX-UHFFFAOYSA-N 0.000 description 2
- 239000000443 aerosol Substances 0.000 description 2
- 150000001335 aliphatic alkanes Chemical group 0.000 description 2
- YXOPSXVJUJPPFD-UHFFFAOYSA-N anisole 4-(4-methoxyphenyl)-4-oxobutanoic acid Chemical compound C1(=CC=CC=C1)OC.O=C(CCC(=O)O)C1=CC=C(C=C1)OC YXOPSXVJUJPPFD-UHFFFAOYSA-N 0.000 description 2
- 238000009835 boiling Methods 0.000 description 2
- ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 description 2
- 230000007885 bronchoconstriction Effects 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- 210000004027 cell Anatomy 0.000 description 2
- 235000019441 ethanol Nutrition 0.000 description 2
- MDKXBBPLEGPIRI-UHFFFAOYSA-N ethoxyethane;methanol Chemical compound OC.CCOCC MDKXBBPLEGPIRI-UHFFFAOYSA-N 0.000 description 2
- 238000011156 evaluation Methods 0.000 description 2
- 239000007789 gas Substances 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- 150000001261 hydroxy acids Chemical class 0.000 description 2
- CGIGDMFJXJATDK-UHFFFAOYSA-N indomethacin Chemical compound CC1=C(CC(O)=O)C2=CC(OC)=CC=C2N1C(=O)C1=CC=C(Cl)C=C1 CGIGDMFJXJATDK-UHFFFAOYSA-N 0.000 description 2
- 239000000543 intermediate Substances 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- 150000002576 ketones Chemical class 0.000 description 2
- 229940046892 lead acetate Drugs 0.000 description 2
- 239000000314 lubricant Substances 0.000 description 2
- YDCHPLOFQATIDS-UHFFFAOYSA-N methyl 2-bromoacetate Chemical compound COC(=O)CBr YDCHPLOFQATIDS-UHFFFAOYSA-N 0.000 description 2
- 238000000465 moulding Methods 0.000 description 2
- 239000012074 organic phase Substances 0.000 description 2
- KJIFKLIQANRMOU-UHFFFAOYSA-N oxidanium;4-methylbenzenesulfonate Chemical compound O.CC1=CC=C(S(O)(=O)=O)C=C1 KJIFKLIQANRMOU-UHFFFAOYSA-N 0.000 description 2
- 230000002093 peripheral effect Effects 0.000 description 2
- NTTOTNSKUYCDAV-UHFFFAOYSA-N potassium hydride Chemical compound [KH] NTTOTNSKUYCDAV-UHFFFAOYSA-N 0.000 description 2
- 229910000105 potassium hydride Inorganic materials 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 230000002441 reversible effect Effects 0.000 description 2
- 229920006395 saturated elastomer Polymers 0.000 description 2
- 235000017550 sodium carbonate Nutrition 0.000 description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 description 2
- 239000012258 stirred mixture Substances 0.000 description 2
- 238000007920 subcutaneous administration Methods 0.000 description 2
- 125000001424 substituent group Chemical group 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- 210000003437 trachea Anatomy 0.000 description 2
- 238000001665 trituration Methods 0.000 description 2
- 239000003039 volatile agent Substances 0.000 description 2
- BHMLFPOTZYRDKA-IRXDYDNUSA-N (2s)-2-[(s)-(2-iodophenoxy)-phenylmethyl]morpholine Chemical compound IC1=CC=CC=C1O[C@@H](C=1C=CC=CC=1)[C@H]1OCCNC1 BHMLFPOTZYRDKA-IRXDYDNUSA-N 0.000 description 1
- RMXLHIUHKIVPAB-OWOJBTEDSA-N (e)-1,4-dibromobut-2-ene Chemical group BrC\C=C\CBr RMXLHIUHKIVPAB-OWOJBTEDSA-N 0.000 description 1
- DYLIWHYUXAJDOJ-OWOJBTEDSA-N (e)-4-(6-aminopurin-9-yl)but-2-en-1-ol Chemical compound NC1=NC=NC2=C1N=CN2C\C=C\CO DYLIWHYUXAJDOJ-OWOJBTEDSA-N 0.000 description 1
- ATWLRNODAYAMQS-UHFFFAOYSA-N 1,1-dibromopropane Chemical compound CCC(Br)Br ATWLRNODAYAMQS-UHFFFAOYSA-N 0.000 description 1
- ZJJATABWMGVVRZ-UHFFFAOYSA-N 1,12-dibromododecane Chemical compound BrCCCCCCCCCCCCBr ZJJATABWMGVVRZ-UHFFFAOYSA-N 0.000 description 1
- UXAFLFGXSIWWMY-UHFFFAOYSA-N 1,3-dibromo-2,2-dimethylpropane Chemical compound BrCC(C)(C)CBr UXAFLFGXSIWWMY-UHFFFAOYSA-N 0.000 description 1
- SMGXHVWYXQYMNN-UHFFFAOYSA-N 1,3-dibromo-2-methylpropane Chemical compound BrCC(C)CBr SMGXHVWYXQYMNN-UHFFFAOYSA-N 0.000 description 1
- XZNGUVQDFJHPLU-UHFFFAOYSA-N 1,3-dibromobutane Chemical compound CC(Br)CCBr XZNGUVQDFJHPLU-UHFFFAOYSA-N 0.000 description 1
- VENSUTAUIFXSRD-UHFFFAOYSA-N 1,3-dichloro-2-methylpropane Chemical group ClCC(C)CCl VENSUTAUIFXSRD-UHFFFAOYSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- ULTHEAFYOOPTTB-UHFFFAOYSA-N 1,4-dibromobutane Chemical compound BrCCCCBr ULTHEAFYOOPTTB-UHFFFAOYSA-N 0.000 description 1
- OCJBOOLMMGQPQU-UHFFFAOYSA-N 1,4-dichlorobenzene Chemical compound ClC1=CC=C(Cl)C=C1 OCJBOOLMMGQPQU-UHFFFAOYSA-N 0.000 description 1
- IBODDUNKEPPBKW-UHFFFAOYSA-N 1,5-dibromopentane Chemical compound BrCCCCCBr IBODDUNKEPPBKW-UHFFFAOYSA-N 0.000 description 1
- LVWSZGCVEZRFBT-UHFFFAOYSA-N 1,7-dibromoheptane Chemical compound BrCCCCCCCBr LVWSZGCVEZRFBT-UHFFFAOYSA-N 0.000 description 1
- DKEGCUDAFWNSSO-UHFFFAOYSA-N 1,8-dibromooctane Chemical compound BrCCCCCCCCBr DKEGCUDAFWNSSO-UHFFFAOYSA-N 0.000 description 1
- WGAXVZXBFBHLMC-UHFFFAOYSA-N 1,9-dibromononane Chemical compound BrCCCCCCCCCBr WGAXVZXBFBHLMC-UHFFFAOYSA-N 0.000 description 1
- YUKILTJWFRTXGB-UHFFFAOYSA-N 1-chloro-3-methoxybenzene Chemical group COC1=CC=CC(Cl)=C1 YUKILTJWFRTXGB-UHFFFAOYSA-N 0.000 description 1
- MFJNOXOAIFNSBX-UHFFFAOYSA-N 1-fluoro-3-methoxybenzene Chemical compound COC1=CC=CC(F)=C1 MFJNOXOAIFNSBX-UHFFFAOYSA-N 0.000 description 1
- RQUBLQRVLBWBLZ-UHFFFAOYSA-N 1-methoxy-2-propylbenzene Chemical group CCCC1=CC=CC=C1OC RQUBLQRVLBWBLZ-UHFFFAOYSA-N 0.000 description 1
- VXRDAMSNTXUHFX-UHFFFAOYSA-N 2,3-dihydroxybutanedioic acid;n,n-dimethyl-2-[6-methyl-2-(4-methylphenyl)imidazo[1,2-a]pyridin-3-yl]acetamide Chemical compound OC(=O)C(O)C(O)C(O)=O.N1=C2C=CC(C)=CN2C(CC(=O)N(C)C)=C1C1=CC=C(C)C=C1.N1=C2C=CC(C)=CN2C(CC(=O)N(C)C)=C1C1=CC=C(C)C=C1 VXRDAMSNTXUHFX-UHFFFAOYSA-N 0.000 description 1
- TXIPVVLKTCCGPA-UHFFFAOYSA-N 2-[3-[2-[[1-(cyclopropanecarbonyl)piperidin-3-yl]amino]pyrimidin-4-yl]-2-quinolin-2-ylimidazol-4-yl]acetonitrile Chemical compound C1(CC1)C(=O)N1CC(CCC1)NC1=NC=CC(=N1)N1C(=NC=C1CC#N)C1=NC2=CC=CC=C2C=C1 TXIPVVLKTCCGPA-UHFFFAOYSA-N 0.000 description 1
- ISPYQTSUDJAMAB-UHFFFAOYSA-N 2-chlorophenol Chemical compound OC1=CC=CC=C1Cl ISPYQTSUDJAMAB-UHFFFAOYSA-N 0.000 description 1
- SMFBODMWKWBFOK-UHFFFAOYSA-N 3-(3-nitrophenyl)-1-phenylprop-2-en-1-one Chemical compound [O-][N+](=O)C1=CC=CC(C=CC(=O)C=2C=CC=CC=2)=C1 SMFBODMWKWBFOK-UHFFFAOYSA-N 0.000 description 1
- SJTBRFHBXDZMPS-UHFFFAOYSA-N 3-fluorophenol Chemical compound OC1=CC=CC(F)=C1 SJTBRFHBXDZMPS-UHFFFAOYSA-N 0.000 description 1
- QMVAZEHZOPDGHA-UHFFFAOYSA-N 3-methoxybenzenethiol Chemical compound COC1=CC=CC(S)=C1 QMVAZEHZOPDGHA-UHFFFAOYSA-N 0.000 description 1
- HPSBBRRZOMSMMY-UHFFFAOYSA-N 3-methyl-4-(4-methylsulfanylphenyl)-4-oxobutanoic acid Chemical compound CSC1=CC=C(C(=O)C(C)CC(O)=O)C=C1 HPSBBRRZOMSMMY-UHFFFAOYSA-N 0.000 description 1
- ZTGIHSPNBGGQOI-UHFFFAOYSA-N 4-(2,3-dimethylphenyl)butanoic acid Chemical compound CC1=CC=CC(CCCC(O)=O)=C1C ZTGIHSPNBGGQOI-UHFFFAOYSA-N 0.000 description 1
- XOFFAQUWHDDYKP-UHFFFAOYSA-N 4-(2-chloro-4-hydroxyphenyl)-4-oxobutanoic acid Chemical compound OC(=O)CCC(=O)C1=CC=C(O)C=C1Cl XOFFAQUWHDDYKP-UHFFFAOYSA-N 0.000 description 1
- XSWHYNUDBHPCLT-UHFFFAOYSA-N 4-(2-hydroxy-4-sulfanylphenyl)-4-oxobutanoic acid Chemical compound OC(=O)CCC(=O)C1=CC=C(S)C=C1O XSWHYNUDBHPCLT-UHFFFAOYSA-N 0.000 description 1
- RVDWUHPNGCQYRK-UHFFFAOYSA-N 4-(4-hydroxy-3-methylphenyl)-4-oxobutanoic acid Chemical compound CC1=CC(C(=O)CCC(O)=O)=CC=C1O RVDWUHPNGCQYRK-UHFFFAOYSA-N 0.000 description 1
- QUZSKACADDWSNJ-UHFFFAOYSA-N 4-(4-hydroxyphenyl)-2,2-dimethyl-4-oxobutanoic acid Chemical compound OC(=O)C(C)(C)CC(=O)C1=CC=C(O)C=C1 QUZSKACADDWSNJ-UHFFFAOYSA-N 0.000 description 1
- WQLMRGSDYFGYBS-UHFFFAOYSA-N 4-[2-hydroxy-4-[1-(3-nitrophenyl)-3-oxo-3-phenylpropyl]sulfanylphenyl]-4-oxobutanoic acid Chemical compound C1=C(O)C(C(=O)CCC(=O)O)=CC=C1SC(C=1C=C(C=CC=1)[N+]([O-])=O)CC(=O)C1=CC=CC=C1 WQLMRGSDYFGYBS-UHFFFAOYSA-N 0.000 description 1
- GUNURDHYYXLLJI-UHFFFAOYSA-N 4-[2-methoxy-4-[1-(3-nitrophenyl)-3-oxo-3-phenylpropyl]sulfanylphenyl]-4-oxobutanoic acid Chemical compound C1=C(C(=O)CCC(O)=O)C(OC)=CC(SC(CC(=O)C=2C=CC=CC=2)C=2C=C(C=CC=2)[N+]([O-])=O)=C1 GUNURDHYYXLLJI-UHFFFAOYSA-N 0.000 description 1
- RHONWRXFSOSQOY-UHFFFAOYSA-N 4-[3-[3-(4-acetyl-3-hydroxy-2-propylphenoxy)propylsulfanyl]phenyl]-4-hydroxy-3,3-dimethylbutanoic acid Chemical compound C1=CC(C(C)=O)=C(O)C(CCC)=C1OCCCSC1=CC=CC(C(O)C(C)(C)CC(O)=O)=C1 RHONWRXFSOSQOY-UHFFFAOYSA-N 0.000 description 1
- PBGAQNBHGWSYHY-UHFFFAOYSA-N 4-[4-(3-bromopropylsulfanyl)phenyl]-4-hydroxy-3,3-dimethylbutanoic acid Chemical compound OC(=O)CC(C)(C)C(O)C1=CC=C(SCCCBr)C=C1 PBGAQNBHGWSYHY-UHFFFAOYSA-N 0.000 description 1
- GJJSNBJZBQCIAH-UHFFFAOYSA-N 4-[4-(3-bromopropylsulfanyl)phenyl]-4-oxobutanoic acid Chemical compound OC(=O)CCC(=O)C1=CC=C(SCCCBr)C=C1 GJJSNBJZBQCIAH-UHFFFAOYSA-N 0.000 description 1
- HLENBODXFWCADN-UHFFFAOYSA-N 4-[4-(dimethylcarbamothioyloxy)phenyl]-4-oxobutanoic acid Chemical compound CN(C)C(=S)OC1=CC=C(C(=O)CCC(O)=O)C=C1 HLENBODXFWCADN-UHFFFAOYSA-N 0.000 description 1
- MJWMWZFELIIXTM-UHFFFAOYSA-N 4-[4-[3-(4-acetyl-3-hydroxy-2-propylphenoxy)-2-hydroxypropyl]sulfonyl-3-fluorophenyl]-4-oxobutanoic acid Chemical compound CCCC1=C(O)C(C(C)=O)=CC=C1OCC(O)CS(=O)(=O)C1=CC=C(C(=O)CCC(O)=O)C=C1F MJWMWZFELIIXTM-UHFFFAOYSA-N 0.000 description 1
- GHCZBPNCHLQEBT-UHFFFAOYSA-N 4-[4-[3-(4-acetyl-3-hydroxy-2-propylphenoxy)-2-methylpropoxy]phenyl]-4-oxobutanoic acid Chemical compound C1=CC(C(C)=O)=C(O)C(CCC)=C1OCC(C)COC1=CC=C(C(=O)CCC(O)=O)C=C1 GHCZBPNCHLQEBT-UHFFFAOYSA-N 0.000 description 1
- XFRWXILXSBRRHM-UHFFFAOYSA-N 4-[4-[3-(4-acetyl-3-hydroxy-2-propylphenoxy)propoxy]-2-fluorophenyl]-4-oxobutanoic acid Chemical compound CCCC1=C(O)C(C(C)=O)=CC=C1OCCCOC1=CC=C(C(=O)CCC(O)=O)C(F)=C1 XFRWXILXSBRRHM-UHFFFAOYSA-N 0.000 description 1
- OFECPAKEKRXOOP-UHFFFAOYSA-N 4-[4-[3-(4-acetyl-3-hydroxy-2-propylphenoxy)propoxy]-3-bromophenyl]-4-hydroxy-3,3-dimethylbutanoic acid Chemical compound CCCC1=C(O)C(C(C)=O)=CC=C1OCCCOC1=CC=C(C(O)C(C)(C)CC(O)=O)C=C1Br OFECPAKEKRXOOP-UHFFFAOYSA-N 0.000 description 1
- WKPYGLGIHMYYIS-UHFFFAOYSA-N 4-[4-[3-(4-acetyl-3-hydroxy-2-propylphenoxy)propoxy]-3-propylphenyl]-3,3-dimethyl-4-oxobutanoic acid Chemical compound CCCC1=CC(C(=O)C(C)(C)CC(O)=O)=CC=C1OCCCOC1=CC=C(C(C)=O)C(O)=C1CCC WKPYGLGIHMYYIS-UHFFFAOYSA-N 0.000 description 1
- ADEDDGIQPCEJFG-UHFFFAOYSA-N 4-[4-[3-(4-acetyl-3-hydroxy-2-propylphenoxy)propoxy]phenyl]-2,2-dimethyl-4-oxobutanoic acid Chemical compound CCCC1=C(O)C(C(C)=O)=CC=C1OCCCOC1=CC=C(C(=O)CC(C)(C)C(O)=O)C=C1 ADEDDGIQPCEJFG-UHFFFAOYSA-N 0.000 description 1
- ANYWTEZVZHEUFD-UHFFFAOYSA-N 4-[4-[3-(4-acetyl-3-hydroxy-2-propylphenoxy)propoxy]phenyl]-4-hydroxy-3-methylbutanoic acid Chemical compound C1=CC(C(C)=O)=C(O)C(CCC)=C1OCCCOC1=CC=C(C(O)C(C)CC(O)=O)C=C1 ANYWTEZVZHEUFD-UHFFFAOYSA-N 0.000 description 1
- QHKNHNZJOXJSCQ-UHFFFAOYSA-N 4-[4-[3-(4-acetyl-3-hydroxy-2-propylphenoxy)propylsulfanyl]-2-hydroxyphenyl]-4-oxobutanoic acid Chemical compound CCCC1=C(O)C(C(C)=O)=CC=C1OCCCSC1=CC=C(C(=O)CCC(O)=O)C(O)=C1 QHKNHNZJOXJSCQ-UHFFFAOYSA-N 0.000 description 1
- FCHBOBFEEOMZHB-UHFFFAOYSA-N 4-[4-[3-(4-acetyl-3-hydroxy-2-propylphenoxy)propylsulfanyl]-3-bromophenyl]-4-hydroxy-3,3-dimethylbutanoic acid Chemical compound CCCC1=C(O)C(C(C)=O)=CC=C1OCCCSC1=CC=C(C(O)C(C)(C)CC(O)=O)C=C1Br FCHBOBFEEOMZHB-UHFFFAOYSA-N 0.000 description 1
- BNBOPNLZEQZLEH-UHFFFAOYSA-N 4-[4-[3-(4-acetyl-3-hydroxy-2-propylphenoxy)propylsulfanyl]-3-chlorophenyl]-3,3-dimethyl-4-oxobutanoic acid Chemical compound CCCC1=C(O)C(C(C)=O)=CC=C1OCCCSC1=CC=C(C(=O)C(C)(C)CC(O)=O)C=C1Cl BNBOPNLZEQZLEH-UHFFFAOYSA-N 0.000 description 1
- OLGFKYLFKQMOQW-UHFFFAOYSA-N 4-[4-[3-(4-acetyl-3-hydroxy-2-propylphenoxy)propylsulfanyl]-3-chlorophenyl]-4-hydroxy-3,3-dimethylbutanoic acid Chemical compound CCCC1=C(O)C(C(C)=O)=CC=C1OCCCSC1=CC=C(C(O)C(C)(C)CC(O)=O)C=C1Cl OLGFKYLFKQMOQW-UHFFFAOYSA-N 0.000 description 1
- RSIVGXXZMJRPBP-UHFFFAOYSA-N 4-[4-[3-(4-acetyl-3-hydroxy-2-propylphenoxy)propylsulfanyl]-3-propylphenyl]-3,3-dimethyl-4-oxobutanoic acid Chemical compound CCCC1=CC(C(=O)C(C)(C)CC(O)=O)=CC=C1SCCCOC1=CC=C(C(C)=O)C(O)=C1CCC RSIVGXXZMJRPBP-UHFFFAOYSA-N 0.000 description 1
- ZWCDJYCFCBIKPR-UHFFFAOYSA-N 4-[4-[3-(4-acetyl-3-hydroxy-2-propylphenoxy)propylsulfanyl]-3-propylphenyl]-4-hydroxy-3,3-dimethylbutanoic acid Chemical compound CCCC1=CC(C(O)C(C)(C)CC(O)=O)=CC=C1SCCCOC1=CC=C(C(C)=O)C(O)=C1CCC ZWCDJYCFCBIKPR-UHFFFAOYSA-N 0.000 description 1
- ARAJRJPBUXNRGT-UHFFFAOYSA-N 4-[4-[3-(4-acetyl-3-hydroxy-2-propylphenoxy)propylsulfanyl]-3-propylphenyl]-4-hydroxy-3-methylbutanoic acid Chemical compound CCCC1=CC(C(O)C(C)CC(O)=O)=CC=C1SCCCOC1=CC=C(C(C)=O)C(O)=C1CCC ARAJRJPBUXNRGT-UHFFFAOYSA-N 0.000 description 1
- QCKZVTHRYSFVFF-UHFFFAOYSA-N 4-[4-[3-(4-acetyl-3-hydroxy-2-propylphenoxy)propylsulfanyl]-3-propylphenyl]-4-oxobutanoic acid Chemical compound CCCC1=CC(C(=O)CCC(O)=O)=CC=C1SCCCOC1=CC=C(C(C)=O)C(O)=C1CCC QCKZVTHRYSFVFF-UHFFFAOYSA-N 0.000 description 1
- LMBDCXGLLVVBLT-UHFFFAOYSA-N 4-[4-[3-(4-acetyl-3-hydroxy-2-propylphenoxy)propylsulfanyl]phenyl]-3,3-dimethyl-4-oxobutanoic acid Chemical compound CCCC1=C(O)C(C(C)=O)=CC=C1OCCCSC1=CC=C(C(=O)C(C)(C)CC(O)=O)C=C1 LMBDCXGLLVVBLT-UHFFFAOYSA-N 0.000 description 1
- GYDFMAMTFPETLY-UHFFFAOYSA-N 4-[4-[3-(4-acetyl-3-hydroxy-2-propylphenoxy)propylsulfonyl]-3-fluorophenyl]-4-oxobutanoic acid Chemical compound CCCC1=C(O)C(C(C)=O)=CC=C1OCCCS(=O)(=O)C1=CC=C(C(=O)CCC(O)=O)C=C1F GYDFMAMTFPETLY-UHFFFAOYSA-N 0.000 description 1
- SGDMHGYVVOYUIC-UHFFFAOYSA-N 4-[4-[3-(4-acetyl-3-hydroxy-2-propylphenoxy)propylsulfonyl]phenyl]-3,3-dimethyl-4-oxobutanoic acid Chemical compound CCCC1=C(O)C(C(C)=O)=CC=C1OCCCS(=O)(=O)C1=CC=C(C(=O)C(C)(C)CC(O)=O)C=C1 SGDMHGYVVOYUIC-UHFFFAOYSA-N 0.000 description 1
- CJBPMONPOUZGRY-UHFFFAOYSA-N 4-[4-[3-(4-acetyl-3-hydroxy-6-methyl-2-propylphenoxy)propylsulfanyl]phenyl]-4-hydroxy-3-methylbutanoic acid Chemical compound CCCC1=C(O)C(C(C)=O)=CC(C)=C1OCCCSC1=CC=C(C(O)C(C)CC(O)=O)C=C1 CJBPMONPOUZGRY-UHFFFAOYSA-N 0.000 description 1
- VYEPXHLYTYTPHX-UHFFFAOYSA-N 4-[4-[3-(4-acetyl-5-chloro-3-hydroxy-2-propylphenoxy)propylsulfanyl]phenyl]-4-hydroxy-3,3-dimethylbutanoic acid Chemical compound CCCC1=C(O)C(C(C)=O)=C(Cl)C=C1OCCCSC1=CC=C(C(O)C(C)(C)CC(O)=O)C=C1 VYEPXHLYTYTPHX-UHFFFAOYSA-N 0.000 description 1
- MKWFMKPENMVZMT-UHFFFAOYSA-N 4-[4-[3-(4-acetyl-5-chloro-3-hydroxy-2-propylphenoxy)propylsulfanyl]phenyl]-4-hydroxy-3-methylbutanoic acid Chemical compound CCCC1=C(O)C(C(C)=O)=C(Cl)C=C1OCCCSC1=CC=C(C(O)C(C)CC(O)=O)C=C1 MKWFMKPENMVZMT-UHFFFAOYSA-N 0.000 description 1
- SXEIGTRAWBUCBE-UHFFFAOYSA-N 4-[4-[3-(4-acetyl-6-chloro-3-hydroxy-2-propylphenoxy)propoxy]phenyl]-4-hydroxy-3,3-dimethylbutanoic acid Chemical compound CCCC1=C(O)C(C(C)=O)=CC(Cl)=C1OCCCOC1=CC=C(C(O)C(C)(C)CC(O)=O)C=C1 SXEIGTRAWBUCBE-UHFFFAOYSA-N 0.000 description 1
- IJJBWKVISPQRRY-UHFFFAOYSA-N 4-[4-[3-(4-acetyl-6-chloro-3-hydroxy-2-propylphenoxy)propylsulfonyl]phenyl]-4-oxobutanoic acid Chemical compound CCCC1=C(O)C(C(C)=O)=CC(Cl)=C1OCCCS(=O)(=O)C1=CC=C(C(=O)CCC(O)=O)C=C1 IJJBWKVISPQRRY-UHFFFAOYSA-N 0.000 description 1
- YCNNUIVTVCRQRQ-UHFFFAOYSA-N 4-[4-[3-(4-acetyl-6-fluoro-3-hydroxy-2-propylphenoxy)propoxy]phenyl]-4-hydroxy-3,3-dimethylbutanoic acid Chemical compound CCCC1=C(O)C(C(C)=O)=CC(F)=C1OCCCOC1=CC=C(C(O)C(C)(C)CC(O)=O)C=C1 YCNNUIVTVCRQRQ-UHFFFAOYSA-N 0.000 description 1
- IYHFIJACTBAUDK-UHFFFAOYSA-N 4-[4-[3-(4-acetyl-6-hydroxy-6-propylcyclohexa-2,4-dien-1-yl)oxypropoxy]-3-chlorophenyl]-3,3-dimethyl-4-oxobutanoic acid Chemical compound CCCC1(O)C=C(C(C)=O)C=CC1OCCCOC1=CC=C(C(=O)C(C)(C)CC(O)=O)C=C1Cl IYHFIJACTBAUDK-UHFFFAOYSA-N 0.000 description 1
- BFPGHQLMXCDMGY-UHFFFAOYSA-N 4-hydroxy-1-phenylpentan-1-one Chemical compound CC(O)CCC(=O)C1=CC=CC=C1 BFPGHQLMXCDMGY-UHFFFAOYSA-N 0.000 description 1
- UZFMOKQJFYMBGY-UHFFFAOYSA-N 4-hydroxy-TEMPO Chemical compound CC1(C)CC(O)CC(C)(C)N1[O] UZFMOKQJFYMBGY-UHFFFAOYSA-N 0.000 description 1
- PIMQQGJMDMAZGT-UHFFFAOYSA-N 4-methylthiobenzaldehyde Chemical compound CC1=CC=C(C=S)C=C1 PIMQQGJMDMAZGT-UHFFFAOYSA-N 0.000 description 1
- KPQOOCVEKWNQOR-UHFFFAOYSA-N 5-[4-[3-(4-acetyl-3-hydroxy-2-propylphenoxy)propylsulfonyl]phenyl]-3H-furan-2-one Chemical compound CCCC1=C(O)C(C(C)=O)=CC=C1OCCCS(=O)(=O)C1=CC=C(C=2OC(=O)CC=2)C=C1 KPQOOCVEKWNQOR-UHFFFAOYSA-N 0.000 description 1
- GMZXLEQWVKCMHF-UHFFFAOYSA-N 6-(3-fluoro-2-hydroxyphenyl)-6-oxohexanoic acid Chemical compound OC(=O)CCCCC(=O)C1=CC=CC(F)=C1O GMZXLEQWVKCMHF-UHFFFAOYSA-N 0.000 description 1
- NPGMAUHZZYLWBJ-UHFFFAOYSA-N 6-(3-fluoro-4-hydroxyphenyl)-6-oxohexanoic acid Chemical compound OC(=O)CCCCC(=O)C1=CC=C(O)C(F)=C1 NPGMAUHZZYLWBJ-UHFFFAOYSA-N 0.000 description 1
- DCOKMRYMESLCSI-UHFFFAOYSA-N 6-[4-[3-(4-acetyl-3-hydroxy-2-propylphenoxy)propoxy]-3-fluorophenyl]-6-oxohexanoic acid Chemical compound CCCC1=C(O)C(C(C)=O)=CC=C1OCCCOC1=CC=C(C(=O)CCCCC(O)=O)C=C1F DCOKMRYMESLCSI-UHFFFAOYSA-N 0.000 description 1
- UMXGAMFWVVRONR-UHFFFAOYSA-N 6-[4-[3-(4-acetyl-3-hydroxy-2-propylphenoxy)propylsulfanyl]phenyl]-6-oxohexanoic acid Chemical compound CCCC1=C(O)C(C(C)=O)=CC=C1OCCCSC1=CC=C(C(=O)CCCCC(O)=O)C=C1 UMXGAMFWVVRONR-UHFFFAOYSA-N 0.000 description 1
- RZHLPXCWZXRTEC-UHFFFAOYSA-N 6-[4-[3-(4-acetyl-3-hydroxy-2-propylphenoxy)propylsulfonyl]phenyl]-6-oxohexanoic acid Chemical compound CCCC1=C(O)C(C(C)=O)=CC=C1OCCCS(=O)(=O)C1=CC=C(C(=O)CCCCC(O)=O)C=C1 RZHLPXCWZXRTEC-UHFFFAOYSA-N 0.000 description 1
- NFLLKCVHYJRNRH-UHFFFAOYSA-N 8-chloro-1,3-dimethyl-7H-purine-2,6-dione 2-(diphenylmethyl)oxy-N,N-dimethylethanamine Chemical compound O=C1N(C)C(=O)N(C)C2=C1NC(Cl)=N2.C=1C=CC=CC=1C(OCCN(C)C)C1=CC=CC=C1 NFLLKCVHYJRNRH-UHFFFAOYSA-N 0.000 description 1
- NLHHRLWOUZZQLW-UHFFFAOYSA-N Acrylonitrile Chemical compound C=CC#N NLHHRLWOUZZQLW-UHFFFAOYSA-N 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 1
- 206010003645 Atopy Diseases 0.000 description 1
- 206010006458 Bronchitis chronic Diseases 0.000 description 1
- FERIUCNNQQJTOY-UHFFFAOYSA-M Butyrate Chemical compound CCCC([O-])=O FERIUCNNQQJTOY-UHFFFAOYSA-M 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- 238000005821 Claisen rearrangement reaction Methods 0.000 description 1
- 229940126062 Compound A Drugs 0.000 description 1
- BUDQDWGNQVEFAC-UHFFFAOYSA-N Dihydropyran Chemical compound C1COC=CC1 BUDQDWGNQVEFAC-UHFFFAOYSA-N 0.000 description 1
- 208000000059 Dyspnea Diseases 0.000 description 1
- 206010013975 Dyspnoeas Diseases 0.000 description 1
- BRLQWZUYTZBJKN-UHFFFAOYSA-N Epichlorohydrin Chemical compound ClCC1CO1 BRLQWZUYTZBJKN-UHFFFAOYSA-N 0.000 description 1
- JOYRKODLDBILNP-UHFFFAOYSA-N Ethyl urethane Chemical compound CCOC(N)=O JOYRKODLDBILNP-UHFFFAOYSA-N 0.000 description 1
- 238000005727 Friedel-Crafts reaction Methods 0.000 description 1
- NLDMNSXOCDLTTB-UHFFFAOYSA-N Heterophylliin A Natural products O1C2COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC2C(OC(=O)C=2C=C(O)C(O)=C(O)C=2)C(O)C1OC(=O)C1=CC(O)=C(O)C(O)=C1 NLDMNSXOCDLTTB-UHFFFAOYSA-N 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- PWWVAXIEGOYWEE-UHFFFAOYSA-N Isophenergan Chemical compound C1=CC=C2N(CC(C)N(C)C)C3=CC=CC=C3SC2=C1 PWWVAXIEGOYWEE-UHFFFAOYSA-N 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 201000004681 Psoriasis Diseases 0.000 description 1
- 206010039085 Rhinitis allergic Diseases 0.000 description 1
- 241000282887 Suidae Species 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
- 229910010066 TiC14 Inorganic materials 0.000 description 1
- CIUQDSCDWFSTQR-UHFFFAOYSA-N [C]1=CC=CC=C1 Chemical compound [C]1=CC=CC=C1 CIUQDSCDWFSTQR-UHFFFAOYSA-N 0.000 description 1
- DKIJPGQZVALBIU-UHFFFAOYSA-N [Cl].[Cs] Chemical compound [Cl].[Cs] DKIJPGQZVALBIU-UHFFFAOYSA-N 0.000 description 1
- 150000008065 acid anhydrides Chemical class 0.000 description 1
- 150000001266 acyl halides Chemical class 0.000 description 1
- PWAXUOGZOSVGBO-UHFFFAOYSA-N adipoyl chloride Chemical compound ClC(=O)CCCCC(Cl)=O PWAXUOGZOSVGBO-UHFFFAOYSA-N 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- 229910000288 alkali metal carbonate Inorganic materials 0.000 description 1
- 150000008041 alkali metal carbonates Chemical class 0.000 description 1
- 208000026935 allergic disease Diseases 0.000 description 1
- 201000010105 allergic rhinitis Diseases 0.000 description 1
- 230000007815 allergy Effects 0.000 description 1
- 229940094070 ambien Drugs 0.000 description 1
- 239000000730 antalgic agent Substances 0.000 description 1
- 230000003266 anti-allergic effect Effects 0.000 description 1
- 230000001088 anti-asthma Effects 0.000 description 1
- 239000002260 anti-inflammatory agent Substances 0.000 description 1
- 229940121363 anti-inflammatory agent Drugs 0.000 description 1
- 239000000043 antiallergic agent Substances 0.000 description 1
- 239000000924 antiasthmatic agent Substances 0.000 description 1
- 239000000739 antihistaminic agent Substances 0.000 description 1
- 229940125715 antihistaminic agent Drugs 0.000 description 1
- 229910052786 argon Inorganic materials 0.000 description 1
- 210000001367 artery Anatomy 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 208000006673 asthma Diseases 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- 229940088007 benadryl Drugs 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 230000036772 blood pressure Effects 0.000 description 1
- UWTDFICHZKXYAC-UHFFFAOYSA-N boron;oxolane Chemical compound [B].C1CCOC1 UWTDFICHZKXYAC-UHFFFAOYSA-N 0.000 description 1
- 210000000621 bronchi Anatomy 0.000 description 1
- 206010006451 bronchitis Diseases 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 210000001715 carotid artery Anatomy 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- LQHZJDPVVDQIFQ-UHFFFAOYSA-M cesium;chloride;hydrate Chemical compound O.[Cl-].[Cs+] LQHZJDPVVDQIFQ-UHFFFAOYSA-M 0.000 description 1
- 238000012512 characterization method Methods 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
- OQNGCCWBHLEQFN-UHFFFAOYSA-N chloroform;hexane Chemical compound ClC(Cl)Cl.CCCCCC OQNGCCWBHLEQFN-UHFFFAOYSA-N 0.000 description 1
- 101150040681 cho1 gene Proteins 0.000 description 1
- 238000011210 chromatographic step Methods 0.000 description 1
- 208000007451 chronic bronchitis Diseases 0.000 description 1
- 229910052681 coesite Inorganic materials 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 239000007891 compressed tablet Substances 0.000 description 1
- 238000007906 compression Methods 0.000 description 1
- 230000006835 compression Effects 0.000 description 1
- 230000008602 contraction Effects 0.000 description 1
- 229910052906 cristobalite Inorganic materials 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 229940117389 dichlorobenzene Drugs 0.000 description 1
- HUPFGZXOMWLGNK-UHFFFAOYSA-N diflunisal Chemical compound C1=C(O)C(C(=O)O)=CC(C=2C(=CC(F)=CC=2)F)=C1 HUPFGZXOMWLGNK-UHFFFAOYSA-N 0.000 description 1
- 229960000616 diflunisal Drugs 0.000 description 1
- 229940043279 diisopropylamine Drugs 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- PCHPORCSPXIHLZ-UHFFFAOYSA-N diphenhydramine hydrochloride Chemical compound [Cl-].C=1C=CC=CC=1C(OCC[NH+](C)C)C1=CC=CC=C1 PCHPORCSPXIHLZ-UHFFFAOYSA-N 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 150000004252 dithioacetals Chemical class 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 229940099182 dramamine Drugs 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 239000000428 dust Substances 0.000 description 1
- 230000002526 effect on cardiovascular system Effects 0.000 description 1
- 230000002500 effect on skin Effects 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 239000002532 enzyme inhibitor Substances 0.000 description 1
- ZRSDQBKGDNPFLT-UHFFFAOYSA-N ethanol;oxolane Chemical compound CCO.C1CCOC1 ZRSDQBKGDNPFLT-UHFFFAOYSA-N 0.000 description 1
- OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- ZPAKPRAICRBAOD-UHFFFAOYSA-N fenbufen Chemical compound C1=CC(C(=O)CCC(=O)O)=CC=C1C1=CC=CC=C1 ZPAKPRAICRBAOD-UHFFFAOYSA-N 0.000 description 1
- 229960001395 fenbufen Drugs 0.000 description 1
- 150000008282 halocarbons Chemical class 0.000 description 1
- 229960001340 histamine Drugs 0.000 description 1
- DKAGJZJALZXOOV-UHFFFAOYSA-N hydrate;hydrochloride Chemical compound O.Cl DKAGJZJALZXOOV-UHFFFAOYSA-N 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- RCCPEORTSYDPMB-UHFFFAOYSA-N hydroxy benzenecarboximidothioate Chemical compound OSC(=N)C1=CC=CC=C1 RCCPEORTSYDPMB-UHFFFAOYSA-N 0.000 description 1
- 229960000905 indomethacin Drugs 0.000 description 1
- 239000003701 inert diluent Substances 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 210000004731 jugular vein Anatomy 0.000 description 1
- 210000000265 leukocyte Anatomy 0.000 description 1
- 238000012417 linear regression Methods 0.000 description 1
- XGZVUEUWXADBQD-UHFFFAOYSA-L lithium carbonate Chemical compound [Li+].[Li+].[O-]C([O-])=O XGZVUEUWXADBQD-UHFFFAOYSA-L 0.000 description 1
- 229910052808 lithium carbonate Inorganic materials 0.000 description 1
- 230000001050 lubricating effect Effects 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- HNQIVZYLYMDVSB-UHFFFAOYSA-N methanesulfonimidic acid Chemical compound CS(N)(=O)=O HNQIVZYLYMDVSB-UHFFFAOYSA-N 0.000 description 1
- HNJJXZKZRAWDPF-UHFFFAOYSA-N methapyrilene Chemical group C=1C=CC=NC=1N(CCN(C)C)CC1=CC=CS1 HNJJXZKZRAWDPF-UHFFFAOYSA-N 0.000 description 1
- BPFPBBXSOXNDDP-UHFFFAOYSA-N methyl 4-(4-hydroxyphenyl)-3,3-dimethyl-4-oxobutanoate Chemical compound COC(=O)CC(C)(C)C(=O)C1=CC=C(O)C=C1 BPFPBBXSOXNDDP-UHFFFAOYSA-N 0.000 description 1
- YJSCLHUKWOGHFF-UHFFFAOYSA-N methyl 4-(4-hydroxyphenyl)-3-methyl-4-oxobutanoate Chemical compound COC(=O)CC(C)C(=O)C1=CC=C(O)C=C1 YJSCLHUKWOGHFF-UHFFFAOYSA-N 0.000 description 1
- PVDDSSCYJCLGOD-UHFFFAOYSA-N methyl 4-(4-hydroxyphenyl)-4-oxobutanoate Chemical group COC(=O)CCC(=O)C1=CC=C(O)C=C1 PVDDSSCYJCLGOD-UHFFFAOYSA-N 0.000 description 1
- HOANBPILMOMINR-UHFFFAOYSA-N methyl 4-(4-methoxyphenyl)-3,3-dimethyl-4-oxobutanoate Chemical compound COC(=O)CC(C)(C)C(=O)C1=CC=C(OC)C=C1 HOANBPILMOMINR-UHFFFAOYSA-N 0.000 description 1
- MATCFOJMMMWYDB-UHFFFAOYSA-N methyl 4-[4-[2-[(4-acetyl-3-hydroxy-2-propylphenoxy)methyl]prop-2-enoxy]phenyl]-4-oxobutanoate Chemical compound CCCC1=C(O)C(C(C)=O)=CC=C1OCC(=C)COC1=CC=C(C(=O)CCC(=O)OC)C=C1 MATCFOJMMMWYDB-UHFFFAOYSA-N 0.000 description 1
- DWBWBDUJADDJQD-UHFFFAOYSA-N methyl 4-[4-[3-(4-acetyl-3-hydroxy-2-propylphenoxy)propoxy]phenyl]-3,3-dimethyl-4-oxobutanoate Chemical compound CCCC1=C(O)C(C(C)=O)=CC=C1OCCCOC1=CC=C(C(=O)C(C)(C)CC(=O)OC)C=C1 DWBWBDUJADDJQD-UHFFFAOYSA-N 0.000 description 1
- BWHXIWKQOLGPMS-UHFFFAOYSA-N methyl 5-chloro-2-formylpentanoate Chemical group COC(=O)C(C=O)CCCCl BWHXIWKQOLGPMS-UHFFFAOYSA-N 0.000 description 1
- UUWVBHZDYFQMBU-UHFFFAOYSA-N methyl 6-[4-(3-bromopropylsulfanyl)phenyl]-6-oxohexanoate Chemical compound COC(=O)CCCCC(=O)C1=CC=C(SCCCBr)C=C1 UUWVBHZDYFQMBU-UHFFFAOYSA-N 0.000 description 1
- UDXADPVZZAZJJR-UHFFFAOYSA-N methyl 6-[4-[3-(4-acetyl-3-hydroxy-2-propylphenoxy)propylsulfanyl]phenyl]-6-oxohexanoate Chemical compound CCCC1=C(O)C(C(C)=O)=CC=C1OCCCSC1=CC=C(C(=O)CCCCC(=O)OC)C=C1 UDXADPVZZAZJJR-UHFFFAOYSA-N 0.000 description 1
- PHWISQNXPLXQRU-UHFFFAOYSA-N n,n-dimethylcarbamothioyl chloride Chemical compound CN(C)C(Cl)=S PHWISQNXPLXQRU-UHFFFAOYSA-N 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 239000000041 non-steroidal anti-inflammatory agent Substances 0.000 description 1
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 1
- 239000007764 o/w emulsion Substances 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 150000004967 organic peroxy acids Chemical class 0.000 description 1
- 229940094443 oxytocics prostaglandins Drugs 0.000 description 1
- ZJVAWPKTWVFKHG-UHFFFAOYSA-N p-Methoxypropiophenone Chemical compound CCC(=O)C1=CC=C(OC)C=C1 ZJVAWPKTWVFKHG-UHFFFAOYSA-N 0.000 description 1
- KLAKIAVEMQMVBT-UHFFFAOYSA-N p-hydroxy-phenacyl alcohol Natural products OCC(=O)C1=CC=C(O)C=C1 KLAKIAVEMQMVBT-UHFFFAOYSA-N 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 229940107333 phenergan Drugs 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- RZWZRACFZGVKFM-UHFFFAOYSA-N propanoyl chloride Chemical compound CCC(Cl)=O RZWZRACFZGVKFM-UHFFFAOYSA-N 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 239000002599 prostaglandin synthase inhibitor Substances 0.000 description 1
- 150000003180 prostaglandins Chemical class 0.000 description 1
- 125000006239 protecting group Chemical group 0.000 description 1
- 230000002685 pulmonary effect Effects 0.000 description 1
- 230000008707 rearrangement Effects 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 230000000241 respiratory effect Effects 0.000 description 1
- 230000029058 respiratory gaseous exchange Effects 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 238000007493 shaping process Methods 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 235000012239 silicon dioxide Nutrition 0.000 description 1
- 208000017520 skin disease Diseases 0.000 description 1
- 210000002460 smooth muscle Anatomy 0.000 description 1
- CAOPTLSAFIQAQV-UHFFFAOYSA-M sodium;4-[4-[3-(4-acetyl-3-hydroxy-2-propylphenoxy)propylsulfanyl]-3-chlorophenyl]-4-hydroxy-3-methylbutanoate Chemical compound [Na+].CCCC1=C(O)C(C(C)=O)=CC=C1OCCCSC1=CC=C(C(O)C(C)CC([O-])=O)C=C1Cl CAOPTLSAFIQAQV-UHFFFAOYSA-M 0.000 description 1
- ANQHFCFPHDBHDF-UHFFFAOYSA-M sodium;4-[4-[3-(4-acetyl-3-hydroxy-2-propylphenoxy)propylsulfanyl]-3-fluorophenyl]-4-hydroxy-3,3-dimethylbutanoate Chemical compound [Na+].CCCC1=C(O)C(C(C)=O)=CC=C1OCCCSC1=CC=C(C(O)C(C)(C)CC([O-])=O)C=C1F ANQHFCFPHDBHDF-UHFFFAOYSA-M 0.000 description 1
- DFNFOMOTNJTFSY-UHFFFAOYSA-M sodium;4-[4-[3-(4-acetyl-3-hydroxy-2-propylphenoxy)propylsulfonyl]phenyl]-4-hydroxy-3-methylbutanoate Chemical compound [Na+].CCCC1=C(O)C(C(C)=O)=CC=C1OCCCS(=O)(=O)C1=CC=C(C(O)C(C)CC([O-])=O)C=C1 DFNFOMOTNJTFSY-UHFFFAOYSA-M 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 229910052682 stishovite Inorganic materials 0.000 description 1
- 229940120904 succinylcholine chloride Drugs 0.000 description 1
- YOEWQQVKRJEPAE-UHFFFAOYSA-L succinylcholine chloride (anhydrous) Chemical compound [Cl-].[Cl-].C[N+](C)(C)CCOC(=O)CCC(=O)OCC[N+](C)(C)C YOEWQQVKRJEPAE-UHFFFAOYSA-L 0.000 description 1
- MLKXDPUZXIRXEP-MFOYZWKCSA-N sulindac Chemical compound CC1=C(CC(O)=O)C2=CC(F)=CC=C2\C1=C/C1=CC=C(S(C)=O)C=C1 MLKXDPUZXIRXEP-MFOYZWKCSA-N 0.000 description 1
- 229960000894 sulindac Drugs 0.000 description 1
- 235000011149 sulphuric acid Nutrition 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 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 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 238000011287 therapeutic dose Methods 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- HNKJADCVZUBCPG-UHFFFAOYSA-N thioanisole Chemical compound CSC1=CC=CC=C1 HNKJADCVZUBCPG-UHFFFAOYSA-N 0.000 description 1
- 150000003595 thromboxanes Chemical class 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- JKVRTUCVPZTEQZ-UHFFFAOYSA-N tributyltin azide Chemical compound CCCC[Sn](CCCC)(CCCC)N=[N+]=[N-] JKVRTUCVPZTEQZ-UHFFFAOYSA-N 0.000 description 1
- 229910052905 tridymite Inorganic materials 0.000 description 1
- 230000001960 triggered effect Effects 0.000 description 1
- YFNKIDBQEZZDLK-UHFFFAOYSA-N triglyme Chemical compound COCCOCCOCCOC YFNKIDBQEZZDLK-UHFFFAOYSA-N 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- 239000003643 water by type Substances 0.000 description 1
- 238000010626 work up procedure Methods 0.000 description 1
- ZXVNMYWKKDOREA-UHFFFAOYSA-N zomepirac Chemical compound C1=C(CC(O)=O)N(C)C(C(=O)C=2C=CC(Cl)=CC=2)=C1C ZXVNMYWKKDOREA-UHFFFAOYSA-N 0.000 description 1
- 229960003414 zomepirac Drugs 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/18—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member
- C07D207/22—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member 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
- C07D207/24—Oxygen or sulfur atoms
- C07D207/26—2-Pyrrolidones
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/16—Otologicals
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C317/00—Sulfones; Sulfoxides
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C323/00—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups
-
- 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
- C07C45/61—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups
- C07C45/67—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton
- C07C45/68—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms
- C07C45/70—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms by reaction with functional groups containing oxygen only in singly bound form
- C07C45/71—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms by reaction with functional groups containing oxygen only in singly bound form being hydroxy groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C59/00—Compounds having carboxyl groups bound to acyclic carbon atoms and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups
- C07C59/40—Unsaturated compounds
- C07C59/76—Unsaturated compounds containing keto groups
- C07C59/90—Unsaturated compounds containing keto groups containing singly bound oxygen-containing groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/30—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members
- C07D207/32—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two 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
- C07D207/33—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two 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 with substituted hydrocarbon radicals, directly attached to ring carbon atoms
-
- 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
- C07D233/66—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 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
- C07D233/72—Two oxygen atoms, e.g. hydantoin
- C07D233/74—Two oxygen atoms, e.g. hydantoin with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to other ring members
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D257/00—Heterocyclic compounds containing rings having four nitrogen atoms as the only ring hetero atoms
- C07D257/02—Heterocyclic compounds containing rings having four nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D257/04—Five-membered rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
- C07D307/34—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D307/56—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D307/58—One oxygen atom, e.g. butenolide
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D317/00—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms
- C07D317/08—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3
- C07D317/10—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 not condensed with other rings
- C07D317/32—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 not condensed with other rings 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
- C07D317/34—Oxygen atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Engineering & Computer Science (AREA)
- General Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Dermatology (AREA)
- Pulmonology (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Furan Compounds (AREA)
- Pyrrole Compounds (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US42233882A | 1982-09-23 | 1982-09-23 | |
| US422,338 | 1982-09-23 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1210770A true CA1210770A (en) | 1986-09-02 |
Family
ID=23674451
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA000437216A Expired CA1210770A (en) | 1982-09-23 | 1983-09-21 | Leukotriene antagonists |
Country Status (15)
| Country | Link |
|---|---|
| EP (1) | EP0104885B1 (instruction) |
| JP (1) | JPS59139342A (instruction) |
| KR (1) | KR840006336A (instruction) |
| AT (1) | ATE20233T1 (instruction) |
| AU (1) | AU557953B2 (instruction) |
| CA (1) | CA1210770A (instruction) |
| DE (1) | DE3363942D1 (instruction) |
| DK (1) | DK432783A (instruction) |
| ES (1) | ES525824A0 (instruction) |
| GR (1) | GR79677B (instruction) |
| IE (1) | IE55971B1 (instruction) |
| IL (1) | IL69691A (instruction) |
| NZ (1) | NZ205559A (instruction) |
| PT (1) | PT77367B (instruction) |
| ZA (1) | ZA837048B (instruction) |
Families Citing this family (23)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5143931A (en) * | 1982-06-24 | 1992-09-01 | Smithkline Beecham Corporation | Leukotriene antagonists containing tetrazolyl groups |
| US5135940A (en) * | 1982-09-23 | 1992-08-04 | Merck Frosst Canada, Inc. | Leukotriene antagonists |
| EP0123541B1 (en) * | 1983-04-21 | 1987-07-22 | Merck Frosst Canada Inc. | Leukotriene antagonists |
| US4820867A (en) * | 1983-04-21 | 1989-04-11 | Merck Frosst Canada, Inc. | Phenoxypropoxy halophenylacetic acids as leukotriene antagonists |
| US4539419A (en) * | 1983-05-02 | 1985-09-03 | Hoffmann-La Roche Inc. | Naphthalenyloxy substituted carboxylic acids |
| EP0156233A3 (en) * | 1984-03-19 | 1986-02-19 | Merck & Co. Inc. | Use of leukotriene antagonists for producing cytoprotective pharmaceutical compositions and process for producing cytoprotective pharmaceutical compositions |
| US4939279A (en) * | 1985-04-19 | 1990-07-03 | Smithkline Beecham Corporation | Leukotriene antagonists |
| US4937253A (en) * | 1985-04-19 | 1990-06-26 | Smithkline Beecham Corporation | Ester prodrugs |
| DE3515278A1 (de) * | 1985-04-27 | 1986-10-30 | Grünenthal GmbH, 5190 Stolberg | Neue benzoesaeurederivate, diese enthaltende arzneimittel und verfahren zur herstellung dieser verbindungen und arzneimittel |
| CA1309557C (en) | 1985-06-18 | 1992-10-27 | Robert N. Young | Leukotriene antagonists |
| US4990526A (en) * | 1985-06-18 | 1991-02-05 | Merck Frosst Canada, Inc. | Leukotriene antagonists, compositions and methods of use thereof |
| ATE90076T1 (de) | 1986-03-27 | 1993-06-15 | Merck Frosst Canada Inc | Tetrahydrocarbazole ester. |
| US4857659A (en) * | 1986-04-28 | 1989-08-15 | Merck Frosst Canada, Inc. | Stereoselective synthesis of leukotriene antagonists |
| PT85110A (en) * | 1986-06-23 | 1987-07-01 | Merck Frosst Canada Inc | Process for preparing benzenealkanoic acid derivatives useful as leukotriene antagonists |
| GB8619956D0 (en) * | 1986-08-15 | 1986-09-24 | Roussel Lab Ltd | Chemical compounds |
| US4906658A (en) * | 1987-04-21 | 1990-03-06 | Merck Frosst Canada, Inc. | Fluoro-sulfones |
| PT87616B (pt) * | 1987-06-24 | 1992-09-30 | Smithkline Beecham Corp | Processo de preparacao de antagonistas do leucotrieno e de composicoes farmaceuticas |
| US4985585A (en) * | 1988-03-07 | 1991-01-15 | Kyorin Pharmaceutical Co., Ltd. | Phenoxyalkylcarboxylic acid derivatives and process for their preparations |
| US4954513A (en) * | 1988-12-23 | 1990-09-04 | Smithkline Beecham Corporation | Leukotriene antagonists |
| US5428033A (en) | 1990-10-12 | 1995-06-27 | Merck Frosst Canada, Inc. | Saturated hydroxyalkylquinoline acids as leukotriene antagonists |
| DE4228201A1 (de) * | 1992-08-25 | 1994-03-03 | Schering Ag | Neue Leukotrien-B¶4¶-Antagonisten, Verfahren zu ihrer Herstellung und ihre Verwendung als Arzneimittel |
| US5410054A (en) * | 1993-07-20 | 1995-04-25 | Merck Frosst Canada, Inc. | Heteroaryl quinolines as inhibitors of leukotriene biosynthesis |
| US20150320705A1 (en) * | 2014-05-08 | 2015-11-12 | Medicinova, Inc. | Method of inhibiting or treating amyotrophic lateral sclerosis with phenoxyalkylcarboxylic acids |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1199871A (en) * | 1967-05-11 | 1970-07-22 | Consolidation Coal Co | Improvements in or relating to Sulfur-Containing Bisphenols |
| JPS508095B1 (instruction) * | 1970-01-22 | 1975-04-02 | ||
| BE788749A (fr) * | 1971-09-13 | 1973-03-13 | Takeda Chemical Industries Ltd | Acide 3-(benzoyl trisubstitue)-propionique et son procede de preparation |
| GB2058785B (en) * | 1979-09-05 | 1983-05-25 | Glaxo Group Ltd | Phenol derivatives |
| US4410548A (en) * | 1980-07-09 | 1983-10-18 | Reckitt & Colman Products Limited | Propanolamine derivatives |
| DE3169761D1 (en) * | 1981-01-09 | 1985-05-09 | Fisons Plc | Phenoxy- and thiophenoxy compounds, methods for their preparation and pharmaceutical formulations containing them |
| FR2509725A1 (fr) * | 1981-07-15 | 1983-01-21 | Choay Sa | (hydroxyalkyl)phenylsulfures, leurs procedes de preparation et compositions pharmaceutiques les contenant |
-
1983
- 1983-09-12 NZ NZ205559A patent/NZ205559A/en unknown
- 1983-09-12 IL IL69691A patent/IL69691A/xx unknown
- 1983-09-16 AU AU19190/83A patent/AU557953B2/en not_active Ceased
- 1983-09-19 KR KR1019830004395A patent/KR840006336A/ko not_active Withdrawn
- 1983-09-21 CA CA000437216A patent/CA1210770A/en not_active Expired
- 1983-09-21 DE DE8383305588T patent/DE3363942D1/de not_active Expired
- 1983-09-21 IE IE2210/83A patent/IE55971B1/xx unknown
- 1983-09-21 AT AT83305588T patent/ATE20233T1/de not_active IP Right Cessation
- 1983-09-21 PT PT77367A patent/PT77367B/pt unknown
- 1983-09-21 GR GR72486A patent/GR79677B/el unknown
- 1983-09-21 EP EP83305588A patent/EP0104885B1/en not_active Expired
- 1983-09-22 DK DK432783A patent/DK432783A/da not_active Application Discontinuation
- 1983-09-22 ZA ZA837048A patent/ZA837048B/xx unknown
- 1983-09-22 ES ES525824A patent/ES525824A0/es active Granted
- 1983-09-24 JP JP58175237A patent/JPS59139342A/ja active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| ATE20233T1 (de) | 1986-06-15 |
| DE3363942D1 (en) | 1986-07-10 |
| ES8503323A1 (es) | 1985-02-16 |
| GR79677B (instruction) | 1984-10-31 |
| AU1919083A (en) | 1984-03-29 |
| ZA837048B (en) | 1985-05-29 |
| KR840006336A (ko) | 1984-11-29 |
| EP0104885B1 (en) | 1986-06-04 |
| PT77367B (en) | 1986-04-21 |
| EP0104885A1 (en) | 1984-04-04 |
| IE55971B1 (en) | 1991-03-13 |
| IE832210L (en) | 1984-03-23 |
| IL69691A (en) | 1988-01-31 |
| PT77367A (en) | 1983-10-01 |
| AU557953B2 (en) | 1987-01-15 |
| JPS59139342A (ja) | 1984-08-10 |
| NZ205559A (en) | 1987-08-31 |
| DK432783A (da) | 1984-05-04 |
| ES525824A0 (es) | 1985-02-16 |
| DK432783D0 (da) | 1983-09-22 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CA1210770A (en) | Leukotriene antagonists | |
| Gill et al. | β-Acylethylation with Ketonic Mannich Bases. The Synthesis of some diketones, ketonic sulfides, nitroketones and pyridines | |
| CA1273349A (en) | Leukotriene antagonists | |
| FR2581993A1 (fr) | Derives de (benzoyl-4 piperidino)-2 phenyl-1 alcanols, leur preparation et leur application en therapeutique | |
| EP0375670B1 (en) | Process for preparing 3-polyfluoroalkylisoxazolylamines | |
| FR2621038A1 (fr) | Derives d'alcadienes, leurs preparations, les medicaments les contenant et produits intermediaires | |
| US5411973A (en) | Therapeutic alcohols | |
| US5089654A (en) | Chalcone derivatives | |
| HU211554A9 (en) | Circulation-active dibenzo/1,5/dioxocin-5-ones | |
| US6403814B1 (en) | Method for synthesizing diaryl-substituted heterocyclic compounds, including tetrahydrofurans | |
| WO1989006230A1 (en) | Cyano-dienes, halopyridines, intermediates and a process for their preparation | |
| JPS6135194B2 (instruction) | ||
| EP0053949B1 (fr) | Procédé nouveau de préparation des tétrahydro-5,6,7,7a-4H-thiéno(3,2-c)pyridinones-2 | |
| JPH07215952A (ja) | カテコール誘導体 | |
| JPS606653A (ja) | 抗高コレステロ−ル血症活性を有する5−チアアルカン酸誘導体 | |
| EP0155079B1 (en) | Acetylene amines and their use as vasodilators and antihypertensives | |
| EP0100257A2 (fr) | Nouveaux dérivés aminoalkyl naphtaléniques, leurs sels d'addition d'acide et le procédé de préparation ainsi que l'application en thérapeutique de ces dérivés et sels | |
| EP0041576B1 (en) | 1-(2,6-dichlorophenyl)-2-quinolinoneimine-3-carboxylic acid, production process therefor and anti-inflammatory and analgesic composition containing the compound | |
| US3962281A (en) | Method of preparing aldehydes | |
| HU195638B (en) | Process for producing leukotriene-antagonistic compounds and pharmaceutical compositions containing them as active components | |
| US20020128491A1 (en) | Method for synthesizing diaryl-substituted heterocyclic compounds, including tetrahydrofurans | |
| CH617195A5 (en) | Process for the preparation of 2-(2-thenyl)-1,4,5-trimethyl-1,2,3,6-tetrahydropyridine and use of the latter for the preparation of 2,4,5-trimethylthieno[3,2-f]morphane | |
| JPH0250113B2 (instruction) | ||
| JPS5922703B2 (ja) | オルト−アミノブチロフエノン誘導体の新規な製造法 | |
| JPH05132478A (ja) | 新規な(1,3−ジチオラン−2−イリデン)メチル フエニルアルカン酸誘導体 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MKEX | Expiry |