IL124866A - נפתיל אצטאמידים כמעכבי sPLA2 - Google Patents
נפתיל אצטאמידים כמעכבי sPLA2Info
- Publication number
- IL124866A IL124866A IL12486696A IL12486696A IL124866A IL 124866 A IL124866 A IL 124866A IL 12486696 A IL12486696 A IL 12486696A IL 12486696 A IL12486696 A IL 12486696A IL 124866 A IL124866 A IL 124866A
- Authority
- IL
- Israel
- Prior art keywords
- hydrogen
- compound
- phenyl
- naphthyl
- alkyl
- Prior art date
Links
- 102000005473 Secretory Phospholipases A2 Human genes 0.000 title claims description 20
- 108010031873 Secretory Phospholipases A2 Proteins 0.000 title claims description 20
- 239000003112 inhibitor Substances 0.000 title description 8
- 150000003869 acetamides Chemical class 0.000 title description 3
- -1 naphthyl acetamide compound Chemical class 0.000 claims abstract description 54
- 150000001875 compounds Chemical class 0.000 claims abstract description 52
- 239000001257 hydrogen Substances 0.000 claims abstract description 31
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 31
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 21
- 150000003839 salts Chemical class 0.000 claims abstract description 15
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 14
- DLFVBJFMPXGRIB-UHFFFAOYSA-N thioacetamide Natural products CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 claims abstract description 14
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 10
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 claims abstract description 10
- 229910006069 SO3H Inorganic materials 0.000 claims abstract description 9
- 125000001424 substituent group Chemical group 0.000 claims abstract description 9
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 8
- 230000002452 interceptive effect Effects 0.000 claims abstract description 8
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims abstract description 7
- 229910018828 PO3H2 Inorganic materials 0.000 claims abstract description 5
- 239000004305 biphenyl Substances 0.000 claims abstract description 5
- 235000010290 biphenyl Nutrition 0.000 claims abstract description 5
- 125000002256 xylenyl group Chemical group C1(C(C=CC=C1)C)(C)* 0.000 claims abstract description 5
- 239000012453 solvate Substances 0.000 claims abstract description 4
- 125000005425 toluyl group Chemical group 0.000 claims abstract description 4
- 125000001624 naphthyl group Chemical group 0.000 claims abstract 5
- 125000002877 alkyl aryl group Chemical group 0.000 claims abstract 4
- 125000003710 aryl alkyl group Chemical group 0.000 claims abstract 4
- 125000000020 sulfo group Chemical group O=S(=O)([*])O[H] 0.000 claims abstract 3
- 235000014113 dietary fatty acids Nutrition 0.000 claims description 10
- 239000000194 fatty acid Substances 0.000 claims description 10
- 229930195729 fatty acid Natural products 0.000 claims description 10
- 150000004665 fatty acids Chemical class 0.000 claims description 10
- 239000003814 drug Substances 0.000 claims description 8
- 230000001404 mediated effect Effects 0.000 claims description 8
- 239000008194 pharmaceutical composition Substances 0.000 claims description 8
- 230000002401 inhibitory effect Effects 0.000 claims description 7
- 206010040070 Septic Shock Diseases 0.000 claims description 6
- 230000036303 septic shock Effects 0.000 claims description 6
- 206010001052 Acute respiratory distress syndrome Diseases 0.000 claims description 5
- 208000013616 Respiratory Distress Syndrome Diseases 0.000 claims description 5
- 206010039085 Rhinitis allergic Diseases 0.000 claims description 5
- 201000010105 allergic rhinitis Diseases 0.000 claims description 5
- 208000006673 asthma Diseases 0.000 claims description 5
- 208000030603 inherited susceptibility to asthma Diseases 0.000 claims description 5
- 208000014674 injury Diseases 0.000 claims description 5
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 5
- 230000008733 trauma Effects 0.000 claims description 5
- 241000124008 Mammalia Species 0.000 claims description 4
- 206010033645 Pancreatitis Diseases 0.000 claims description 4
- 208000011341 adult acute respiratory distress syndrome Diseases 0.000 claims description 4
- 201000000028 adult respiratory distress syndrome Diseases 0.000 claims description 4
- 239000003085 diluting agent Substances 0.000 claims description 4
- 239000000651 prodrug Chemical class 0.000 claims description 4
- 229940002612 prodrug Drugs 0.000 claims description 4
- 229940126062 Compound A Drugs 0.000 claims description 3
- 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 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 3
- 230000001575 pathological effect Effects 0.000 claims description 3
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims 3
- 125000003545 alkoxy group Chemical group 0.000 claims 2
- 125000001188 haloalkyl group Chemical group 0.000 claims 2
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims 2
- 238000004519 manufacturing process Methods 0.000 claims 2
- 125000004414 alkyl thio group Chemical group 0.000 claims 1
- 125000000753 cycloalkyl group Chemical group 0.000 claims 1
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 abstract description 3
- 239000000203 mixture Substances 0.000 description 37
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 30
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 28
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 28
- 239000004480 active ingredient Substances 0.000 description 25
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 23
- 239000000243 solution Substances 0.000 description 18
- 239000000047 product Substances 0.000 description 17
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 17
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 15
- 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 14
- 238000006243 chemical reaction Methods 0.000 description 14
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 14
- 238000002360 preparation method Methods 0.000 description 14
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 13
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 13
- 239000002904 solvent Substances 0.000 description 13
- 239000003826 tablet Substances 0.000 description 13
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 12
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 12
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Natural products OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 12
- 238000009472 formulation Methods 0.000 description 12
- 238000000034 method Methods 0.000 description 12
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 12
- 239000007787 solid Substances 0.000 description 12
- 239000011541 reaction mixture Substances 0.000 description 11
- 238000003756 stirring Methods 0.000 description 11
- 229920002472 Starch Polymers 0.000 description 10
- QARVLSVVCXYDNA-UHFFFAOYSA-N bromobenzene Chemical class BrC1=CC=CC=C1 QARVLSVVCXYDNA-UHFFFAOYSA-N 0.000 description 10
- 239000008107 starch Substances 0.000 description 10
- 235000019698 starch Nutrition 0.000 description 10
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 9
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 8
- 239000002253 acid Substances 0.000 description 8
- 238000000921 elemental analysis Methods 0.000 description 8
- 230000005764 inhibitory process Effects 0.000 description 8
- 238000011282 treatment Methods 0.000 description 8
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 7
- 229940114079 arachidonic acid Drugs 0.000 description 7
- 235000021342 arachidonic acid Nutrition 0.000 description 7
- 238000003556 assay Methods 0.000 description 7
- 239000012267 brine Substances 0.000 description 7
- 235000019359 magnesium stearate Nutrition 0.000 description 7
- 239000000741 silica gel Substances 0.000 description 7
- 229910002027 silica gel Inorganic materials 0.000 description 7
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 7
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 6
- MTHSVFCYNBDYFN-UHFFFAOYSA-N diethylene glycol Chemical compound OCCOCCO MTHSVFCYNBDYFN-UHFFFAOYSA-N 0.000 description 6
- 238000000605 extraction Methods 0.000 description 6
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 6
- 235000019341 magnesium sulphate Nutrition 0.000 description 6
- 239000003921 oil Substances 0.000 description 6
- 229910000027 potassium carbonate Inorganic materials 0.000 description 6
- 239000000843 powder Substances 0.000 description 6
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 5
- 239000004615 ingredient Substances 0.000 description 5
- 238000004949 mass spectrometry Methods 0.000 description 5
- 150000002825 nitriles Chemical class 0.000 description 5
- 239000012044 organic layer Substances 0.000 description 5
- 238000010992 reflux Methods 0.000 description 5
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-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
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 4
- 229960000583 acetic acid Drugs 0.000 description 4
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 4
- 150000001350 alkyl halides Chemical class 0.000 description 4
- 239000002585 base Substances 0.000 description 4
- 239000002775 capsule Substances 0.000 description 4
- 239000001768 carboxy methyl cellulose Substances 0.000 description 4
- 238000004587 chromatography analysis Methods 0.000 description 4
- 239000010410 layer Substances 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 4
- 239000002798 polar solvent Substances 0.000 description 4
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 4
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 4
- 239000007858 starting material Substances 0.000 description 4
- 239000006188 syrup Substances 0.000 description 4
- 235000020357 syrup Nutrition 0.000 description 4
- 239000000454 talc Substances 0.000 description 4
- 229910052623 talc Inorganic materials 0.000 description 4
- 235000012222 talc Nutrition 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 4
- 230000001225 therapeutic effect Effects 0.000 description 4
- OZAIFHULBGXAKX-UHFFFAOYSA-N 2,2'-azo-bis-isobutyronitrile Substances N#CC(C)(C)N=NC(C)(C)C#N OZAIFHULBGXAKX-UHFFFAOYSA-N 0.000 description 3
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 3
- VOPWNXZWBYDODV-UHFFFAOYSA-N Chlorodifluoromethane Chemical compound FC(F)Cl VOPWNXZWBYDODV-UHFFFAOYSA-N 0.000 description 3
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 3
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
- 239000000443 aerosol Substances 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 3
- 239000003054 catalyst Substances 0.000 description 3
- 229920002678 cellulose Polymers 0.000 description 3
- 239000001913 cellulose Substances 0.000 description 3
- 235000010980 cellulose Nutrition 0.000 description 3
- 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 3
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 239000000796 flavoring agent Substances 0.000 description 3
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 3
- 239000003960 organic solvent Substances 0.000 description 3
- NNFCIKHAZHQZJG-UHFFFAOYSA-N potassium cyanide Chemical compound [K+].N#[C-] NNFCIKHAZHQZJG-UHFFFAOYSA-N 0.000 description 3
- 239000011535 reaction buffer Substances 0.000 description 3
- 230000002829 reductive effect Effects 0.000 description 3
- 229910052708 sodium Inorganic materials 0.000 description 3
- 239000011734 sodium Substances 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- GPRLSGONYQIRFK-MNYXATJNSA-N triton Chemical compound [3H+] GPRLSGONYQIRFK-MNYXATJNSA-N 0.000 description 3
- YCXGQWQAOFFTIL-UHFFFAOYSA-N 2-(4-phenoxynaphthalen-1-yl)acetic acid Chemical compound C12=CC=CC=C2C(CC(=O)O)=CC=C1OC1=CC=CC=C1 YCXGQWQAOFFTIL-UHFFFAOYSA-N 0.000 description 2
- KIUMMUBSPKGMOY-UHFFFAOYSA-N 3,3'-Dithiobis(6-nitrobenzoic acid) Chemical compound C1=C([N+]([O-])=O)C(C(=O)O)=CC(SSC=2C=C(C(=CC=2)[N+]([O-])=O)C(O)=O)=C1 KIUMMUBSPKGMOY-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 239000005711 Benzoic acid Substances 0.000 description 2
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 2
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- 239000004215 Carbon black (E152) Substances 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- 108010010803 Gelatin Proteins 0.000 description 2
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 2
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 2
- 102000006447 Phospholipases A2 Human genes 0.000 description 2
- 108010058864 Phospholipases A2 Proteins 0.000 description 2
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
- 235000021355 Stearic acid Nutrition 0.000 description 2
- JFIRWDCBJXNJFI-SANMLTNESA-N [(2s)-2,3-bis(decanoylsulfanyl)propyl] 2-(trimethylazaniumyl)ethyl phosphate Chemical compound CCCCCCCCCC(=O)SC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)SC(=O)CCCCCCCCC JFIRWDCBJXNJFI-SANMLTNESA-N 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- 125000000304 alkynyl group Chemical group 0.000 description 2
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 2
- 235000010233 benzoic acid Nutrition 0.000 description 2
- 239000011230 binding agent Substances 0.000 description 2
- 125000004432 carbon atom Chemical group C* 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
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- 229930195733 hydrocarbon Natural products 0.000 description 2
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- 230000007062 hydrolysis Effects 0.000 description 2
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- 239000011777 magnesium Substances 0.000 description 2
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- ZGEGCLOFRBLKSE-UHFFFAOYSA-N methylene hexane Natural products CCCCCC=C ZGEGCLOFRBLKSE-UHFFFAOYSA-N 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 239000002808 molecular sieve Substances 0.000 description 2
- CXAYOCVHDCXPAI-UHFFFAOYSA-N naphthalen-1-yl(phenyl)methanone Chemical compound C=1C=CC2=CC=CC=C2C=1C(=O)C1=CC=CC=C1 CXAYOCVHDCXPAI-UHFFFAOYSA-N 0.000 description 2
- YJMNOKOLADGBKA-UHFFFAOYSA-N naphthalene-1-carbonitrile Chemical compound C1=CC=C2C(C#N)=CC=CC2=C1 YJMNOKOLADGBKA-UHFFFAOYSA-N 0.000 description 2
- 239000012299 nitrogen atmosphere Substances 0.000 description 2
- 231100000252 nontoxic Toxicity 0.000 description 2
- 230000003000 nontoxic effect Effects 0.000 description 2
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 150000002989 phenols Chemical class 0.000 description 2
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 2
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 2
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 2
- 230000003389 potentiating effect Effects 0.000 description 2
- LVTJOONKWUXEFR-FZRMHRINSA-N protoneodioscin Natural products O(C[C@@H](CC[C@]1(O)[C@H](C)[C@@H]2[C@]3(C)[C@H]([C@H]4[C@@H]([C@]5(C)C(=CC4)C[C@@H](O[C@@H]4[C@H](O[C@H]6[C@@H](O)[C@@H](O)[C@@H](O)[C@H](C)O6)[C@@H](O)[C@H](O[C@H]6[C@@H](O)[C@@H](O)[C@@H](O)[C@H](C)O6)[C@H](CO)O4)CC5)CC3)C[C@@H]2O1)C)[C@H]1[C@H](O)[C@H](O)[C@H](O)[C@@H](CO)O1 LVTJOONKWUXEFR-FZRMHRINSA-N 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 description 2
- 229910052938 sodium sulfate Inorganic materials 0.000 description 2
- 235000011152 sodium sulphate Nutrition 0.000 description 2
- 239000008117 stearic acid Substances 0.000 description 2
- KZNICNPSHKQLFF-UHFFFAOYSA-N succinimide Chemical compound O=C1CCC(=O)N1 KZNICNPSHKQLFF-UHFFFAOYSA-N 0.000 description 2
- 239000000829 suppository Substances 0.000 description 2
- 210000001179 synovial fluid Anatomy 0.000 description 2
- 238000010792 warming Methods 0.000 description 2
- 238000005303 weighing Methods 0.000 description 2
- 125000006727 (C1-C6) alkenyl group Chemical group 0.000 description 1
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 description 1
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- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- 230000000269 nucleophilic effect Effects 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 229940049964 oleate Drugs 0.000 description 1
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 238000012261 overproduction Methods 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 229940014662 pantothenate Drugs 0.000 description 1
- 235000019161 pantothenic acid Nutrition 0.000 description 1
- 239000011713 pantothenic acid Substances 0.000 description 1
- 239000001814 pectin Substances 0.000 description 1
- 235000010987 pectin Nutrition 0.000 description 1
- 229920001277 pectin Polymers 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 150000002978 peroxides Chemical class 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 150000003904 phospholipids Chemical class 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 239000003380 propellant Substances 0.000 description 1
- 125000004368 propenyl group Chemical group C(=CC)* 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- MWWATHDPGQKSAR-UHFFFAOYSA-N propyne Chemical group CC#C MWWATHDPGQKSAR-UHFFFAOYSA-N 0.000 description 1
- 239000003586 protic polar solvent Substances 0.000 description 1
- 239000008213 purified water Substances 0.000 description 1
- 125000001453 quaternary ammonium group Chemical group 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 238000003259 recombinant expression Methods 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- YGSDEFSMJLZEOE-UHFFFAOYSA-M salicylate Chemical compound OC1=CC=CC=C1C([O-])=O YGSDEFSMJLZEOE-UHFFFAOYSA-M 0.000 description 1
- 229960001860 salicylate Drugs 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 239000012056 semi-solid material Substances 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 229910000104 sodium hydride Inorganic materials 0.000 description 1
- 239000011343 solid material Substances 0.000 description 1
- 238000002798 spectrophotometry method Methods 0.000 description 1
- 229910001220 stainless steel Inorganic materials 0.000 description 1
- 239000010935 stainless steel Substances 0.000 description 1
- 239000008223 sterile water Substances 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 229960002317 succinimide Drugs 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- 150000003555 thioacetals Chemical class 0.000 description 1
- 125000002813 thiocarbonyl group Chemical group *C(*)=S 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 1
- 229940070710 valerate Drugs 0.000 description 1
- NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical compound CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 239000001993 wax Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C235/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms
- C07C235/02—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to acyclic carbon atoms and singly-bound oxygen atoms bound to the same carbon skeleton
- C07C235/32—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to acyclic carbon atoms and singly-bound oxygen atoms bound to the same carbon skeleton the carbon skeleton containing six-membered aromatic rings
- C07C235/34—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to acyclic carbon atoms and singly-bound oxygen atoms bound to the same carbon skeleton the carbon skeleton containing six-membered aromatic rings having the nitrogen atoms of the carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C229/00—Compounds containing amino and carboxyl groups bound to the same carbon skeleton
- C07C229/02—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton
- C07C229/04—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated
- C07C229/06—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated having only one amino and one carboxyl group bound to the carbon skeleton
- C07C229/08—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated having only one amino and one carboxyl group bound to the carbon skeleton the nitrogen atom of the amino group being further bound to hydrogen atoms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/16—Amides, e.g. hydroxamic acids
- A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/18—Drugs for disorders of the alimentary tract or the digestive system for pancreatic disorders, e.g. pancreatic enzymes
-
- 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
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/02—Nasal agents, e.g. decongestants
-
- 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
- A61P11/06—Antiasthmatics
-
- 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
-
- 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
- C07C233/00—Carboxylic acid amides
- C07C233/01—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
- C07C233/02—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having nitrogen atoms of carboxamide groups bound to hydrogen atoms or to carbon atoms of unsubstituted hydrocarbon radicals
- C07C233/11—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having nitrogen atoms of carboxamide groups bound to hydrogen atoms or to carbon atoms of unsubstituted hydrocarbon radicals with carbon atoms of carboxamide groups bound to carbon atoms of an unsaturated carbon skeleton containing six-membered aromatic rings
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Pulmonology (AREA)
- Immunology (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Otolaryngology (AREA)
- Epidemiology (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Indole Compounds (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US855895P | 1995-12-13 | 1995-12-13 | |
| GBGB9602267.8A GB9602267D0 (en) | 1996-02-05 | 1996-02-05 | Naphthyl acetamides as sPLA2 inhibitors |
| PCT/US1996/019874 WO1997021664A1 (en) | 1995-12-13 | 1996-12-09 | NAPHTHYL ACETAMIDES AS sPLA2 INHIBITORS |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| IL124866A0 IL124866A0 (en) | 1999-01-26 |
| IL124866A true IL124866A (he) | 2002-08-14 |
Family
ID=26308607
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| IL12486696A IL124866A (he) | 1995-12-13 | 1996-12-09 | נפתיל אצטאמידים כמעכבי sPLA2 |
Country Status (17)
| Country | Link |
|---|---|
| US (1) | US6160175A (he) |
| EP (1) | EP0779271B1 (he) |
| JP (1) | JP2000501739A (he) |
| KR (1) | KR19990072110A (he) |
| AT (1) | ATE203744T1 (he) |
| AU (1) | AU1289797A (he) |
| BR (1) | BR9612347A (he) |
| CA (1) | CA2240395A1 (he) |
| DE (1) | DE69614232T2 (he) |
| DK (1) | DK0779271T3 (he) |
| ES (1) | ES2159347T3 (he) |
| GR (1) | GR3036988T3 (he) |
| HU (1) | HUP9901984A3 (he) |
| IL (1) | IL124866A (he) |
| MX (1) | MX9804751A (he) |
| PT (1) | PT779271E (he) |
| WO (1) | WO1997021664A1 (he) |
Families Citing this family (17)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6177440B1 (en) | 1996-10-30 | 2001-01-23 | Eli Lilly And Company | Substituted tricyclics |
| US6713645B1 (en) * | 1996-10-30 | 2004-03-30 | Eli Lilly And Company | Substituted tricyclics |
| US5916922A (en) * | 1996-12-03 | 1999-06-29 | Eli Lilly And Company | Phenyl glyoxamides as SPLA2 inhibitors |
| US6353128B1 (en) | 1996-12-03 | 2002-03-05 | Eli Lilly And Company | Phenyl acetamides as sPLA2 inhibitors |
| HUP0102981A3 (en) | 1998-03-31 | 2002-10-28 | Shionogi & Co | Pyrrolo[1,2-a]pyrazine derivatives and pharmaceutical compositions thereof |
| ID23219A (id) * | 1998-04-17 | 2000-03-30 | Lilly Co Eli | Trisiklik tersubstitusi |
| DZ2769A1 (fr) * | 1998-04-17 | 2003-12-01 | Lilly Co Eli | Composés tricycliques substitués. |
| AU748787B2 (en) | 1998-05-21 | 2002-06-13 | Shionogi & Co., Ltd. | Pyrrolo(1,2-b)pyridazine derivatives having sPLA2 inhibitory effect |
| EP1157704B1 (en) | 1998-10-14 | 2006-06-14 | Shionogi & Co., Ltd. | Spla2 inhibitors for the treatment of ischaemic reperfusion injury |
| US6703385B1 (en) | 1999-07-19 | 2004-03-09 | Shionogi & Co., Ltd. | Tricyclic compounds having sPLA2-inhibitory activities |
| US6673781B1 (en) | 1999-08-02 | 2004-01-06 | Shionogi & Co., Ltd. | Tricyclic compounds having sPLA2-inhibitory activities |
| US6787545B1 (en) | 1999-08-23 | 2004-09-07 | Shiongi & Co., Ltd. | Pyrrolotriazine derivatives having spla2-inhibitory activities |
| AU1304801A (en) | 1999-11-15 | 2001-05-30 | Shionogi & Co., Ltd. | Tricyclic azaindolizine derivatives having an SPLA2- inhibiting effect |
| AU2001267823A1 (en) | 2000-06-29 | 2002-01-08 | Shionogi And Co., Ltd. | Compounds exhibiting x-type spla2 inhibiting effect |
| AU2001267825A1 (en) | 2000-06-29 | 2002-01-08 | Shionogi And Co., Ltd. | Remedies for cirrhosis |
| TWI314457B (he) | 2001-03-19 | 2009-09-11 | Shionogi & Co | |
| US20060064279A1 (en) * | 2004-09-17 | 2006-03-23 | Eric Baum | Algorithm for retrieval of ocean surface temperature, wind speed and wind direction from remote microwave radiometric measurements |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3820463A1 (de) * | 1988-06-16 | 1989-12-21 | Basf Ag | Strahlungsempfindliche, ethylenisch ungesaettigte, copolymerisierbare verbindungen und verfahren zu deren herstellung |
| FR2658818B1 (fr) * | 1990-02-27 | 1993-12-31 | Adir Cie | Nouveaux derives a structure naphtalenique, leur procede de preparation et les compositions pharmaceutiques qui les contiennent. |
-
1996
- 1996-12-09 HU HU9901984A patent/HUP9901984A3/hu unknown
- 1996-12-09 AT AT96308915T patent/ATE203744T1/de not_active IP Right Cessation
- 1996-12-09 KR KR1019980704425A patent/KR19990072110A/ko not_active Application Discontinuation
- 1996-12-09 JP JP9522227A patent/JP2000501739A/ja not_active Ceased
- 1996-12-09 WO PCT/US1996/019874 patent/WO1997021664A1/en not_active Application Discontinuation
- 1996-12-09 US US09/091,077 patent/US6160175A/en not_active Expired - Fee Related
- 1996-12-09 BR BR9612347A patent/BR9612347A/pt not_active Application Discontinuation
- 1996-12-09 DK DK96308915T patent/DK0779271T3/da active
- 1996-12-09 EP EP96308915A patent/EP0779271B1/en not_active Expired - Lifetime
- 1996-12-09 IL IL12486696A patent/IL124866A/he not_active IP Right Cessation
- 1996-12-09 CA CA002240395A patent/CA2240395A1/en not_active Abandoned
- 1996-12-09 AU AU12897/97A patent/AU1289797A/en not_active Abandoned
- 1996-12-09 DE DE69614232T patent/DE69614232T2/de not_active Expired - Fee Related
- 1996-12-09 PT PT96308915T patent/PT779271E/pt unknown
- 1996-12-09 ES ES96308915T patent/ES2159347T3/es not_active Expired - Lifetime
-
1998
- 1998-06-12 MX MX9804751A patent/MX9804751A/es not_active IP Right Cessation
-
2001
- 2001-10-24 GR GR20010401861T patent/GR3036988T3/el not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| GR3036988T3 (en) | 2002-01-31 |
| AU1289797A (en) | 1997-07-03 |
| PT779271E (pt) | 2001-11-30 |
| DE69614232T2 (de) | 2002-01-10 |
| ES2159347T3 (es) | 2001-10-01 |
| KR19990072110A (ko) | 1999-09-27 |
| MX9804751A (es) | 1998-10-31 |
| JP2000501739A (ja) | 2000-02-15 |
| EP0779271B1 (en) | 2001-08-01 |
| ATE203744T1 (de) | 2001-08-15 |
| CA2240395A1 (en) | 1997-06-19 |
| HUP9901984A3 (en) | 2001-01-29 |
| US6160175A (en) | 2000-12-12 |
| BR9612347A (pt) | 1999-07-13 |
| DE69614232D1 (de) | 2001-09-06 |
| IL124866A0 (en) | 1999-01-26 |
| EP0779271A1 (en) | 1997-06-18 |
| HUP9901984A2 (hu) | 1999-10-28 |
| WO1997021664A1 (en) | 1997-06-19 |
| DK0779271T3 (da) | 2001-10-08 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FF | Patent granted | ||
| RH1 | Patent not in force |