NO313193B1 - Nye forbindelser for anvendelse som neuro-protektive midler - Google Patents
Nye forbindelser for anvendelse som neuro-protektive midler Download PDFInfo
- Publication number
- NO313193B1 NO313193B1 NO19992226A NO992226A NO313193B1 NO 313193 B1 NO313193 B1 NO 313193B1 NO 19992226 A NO19992226 A NO 19992226A NO 992226 A NO992226 A NO 992226A NO 313193 B1 NO313193 B1 NO 313193B1
- Authority
- NO
- Norway
- Prior art keywords
- mmol
- alkyl
- butyl
- ethyl
- hydroxyphenyl
- Prior art date
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- 150000001875 compounds Chemical class 0.000 title claims description 344
- 239000004090 neuroprotective agent Substances 0.000 title abstract description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 187
- -1 4,5-dihydro-1H-imidazol-2-yl Chemical group 0.000 claims description 97
- 125000000217 alkyl group Chemical group 0.000 claims description 71
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 50
- 125000001424 substituent group Chemical group 0.000 claims description 47
- 229910052739 hydrogen Inorganic materials 0.000 claims description 29
- 239000001257 hydrogen Substances 0.000 claims description 28
- 229910052736 halogen Inorganic materials 0.000 claims description 27
- 150000002367 halogens Chemical class 0.000 claims description 26
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 26
- 125000004076 pyridyl group Chemical group 0.000 claims description 24
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 21
- 229910052799 carbon Inorganic materials 0.000 claims description 17
- 125000004194 piperazin-1-yl group Chemical group [H]N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 claims description 17
- 150000003839 salts Chemical class 0.000 claims description 16
- HRDXJKGNWSUIBT-UHFFFAOYSA-N methoxybenzene Chemical group [CH2]OC1=CC=CC=C1 HRDXJKGNWSUIBT-UHFFFAOYSA-N 0.000 claims description 9
- 125000004432 carbon atom Chemical group C* 0.000 claims description 8
- 125000002962 imidazol-1-yl group Chemical group [*]N1C([H])=NC([H])=C1[H] 0.000 claims description 8
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 8
- 125000005942 tetrahydropyridyl group Chemical group 0.000 claims description 8
- 230000003287 optical effect Effects 0.000 claims description 7
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 6
- 125000001712 tetrahydronaphthyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 claims description 6
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 5
- 239000003085 diluting agent Substances 0.000 claims description 4
- 150000002431 hydrogen Chemical class 0.000 claims description 4
- 125000005322 morpholin-1-yl group Chemical group 0.000 claims description 4
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 4
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 4
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 4
- 125000004571 thiomorpholin-4-yl group Chemical group N1(CCSCC1)* 0.000 claims description 4
- KDAMEDBSALVTNT-UHFFFAOYSA-N 2,6-ditert-butyl-4-[4-[2-[4-ethyl-2-[2-(propylamino)ethyl]phenoxy]ethyl]-1,3-oxazol-2-yl]phenol Chemical compound C(C)(C)(C)C=1C=C(C=C(C1O)C(C)(C)C)C=1OC=C(N1)CCOC1=C(C=C(C=C1)CC)CCNCCC KDAMEDBSALVTNT-UHFFFAOYSA-N 0.000 claims description 3
- 239000000969 carrier Substances 0.000 claims description 3
- LPCSFBYROVBGJU-UHFFFAOYSA-N 2,6-ditert-butyl-4-[5-[2-[4-[[ethyl(methyl)amino]methyl]phenoxy]ethyl]-4,5-dihydro-1,3-oxazol-2-yl]cyclohexa-1,4-dien-1-olate hydrochloride Chemical group Cl.CCN(C)Cc1ccc(OCCC2CN=C(O2)[C+]2CC(=C([O-])C(=C2)C(C)(C)C)C(C)(C)C)cc1 LPCSFBYROVBGJU-UHFFFAOYSA-N 0.000 claims 1
- RQCBPOPQTLHDFC-UHFFFAOYSA-N 2-phenyl-1,3-oxazole Chemical class C1=COC(C=2C=CC=CC=2)=N1 RQCBPOPQTLHDFC-UHFFFAOYSA-N 0.000 abstract description 35
- 150000000183 1,3-benzoxazoles Chemical class 0.000 abstract description 2
- 150000004866 oxadiazoles Chemical class 0.000 abstract description 2
- 150000002918 oxazolines Chemical class 0.000 abstract description 2
- 150000003557 thiazoles Chemical class 0.000 abstract description 2
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 472
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 281
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 253
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 176
- 239000000243 solution Substances 0.000 description 164
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 150
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 148
- 239000011541 reaction mixture Substances 0.000 description 139
- 238000005160 1H NMR spectroscopy Methods 0.000 description 133
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 113
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 101
- 239000000047 product Substances 0.000 description 99
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 97
- 238000000434 field desorption mass spectrometry Methods 0.000 description 96
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 90
- 229910001868 water Inorganic materials 0.000 description 89
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 88
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 88
- 239000003921 oil Substances 0.000 description 87
- 239000012267 brine Substances 0.000 description 85
- 238000002360 preparation method Methods 0.000 description 85
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 85
- 238000000921 elemental analysis Methods 0.000 description 81
- 229910052938 sodium sulfate Inorganic materials 0.000 description 81
- 235000011152 sodium sulphate Nutrition 0.000 description 81
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 80
- ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 description 76
- 239000000463 material Substances 0.000 description 76
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 74
- 238000006243 chemical reaction Methods 0.000 description 72
- 239000000203 mixture Substances 0.000 description 66
- 239000012044 organic layer Substances 0.000 description 66
- 239000006260 foam Substances 0.000 description 64
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 61
- 239000000706 filtrate Substances 0.000 description 61
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 57
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 56
- 239000000725 suspension Substances 0.000 description 56
- 238000001819 mass spectrum Methods 0.000 description 53
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 51
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 51
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 51
- 238000000034 method Methods 0.000 description 49
- 238000003756 stirring Methods 0.000 description 49
- 239000000543 intermediate Substances 0.000 description 46
- 229910052757 nitrogen Inorganic materials 0.000 description 45
- 239000000741 silica gel Substances 0.000 description 45
- 229910002027 silica gel Inorganic materials 0.000 description 45
- 239000007789 gas Substances 0.000 description 44
- 238000004237 preparative chromatography Methods 0.000 description 41
- 238000011282 treatment Methods 0.000 description 37
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 36
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 36
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 35
- KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 description 35
- 239000000908 ammonium hydroxide Substances 0.000 description 34
- 239000012458 free base Substances 0.000 description 34
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 33
- 239000012071 phase Substances 0.000 description 32
- 238000000746 purification Methods 0.000 description 32
- LIWAQLJGPBVORC-UHFFFAOYSA-N ethylmethylamine Chemical compound CCNC LIWAQLJGPBVORC-UHFFFAOYSA-N 0.000 description 31
- 229920006395 saturated elastomer Polymers 0.000 description 31
- 239000007787 solid Substances 0.000 description 31
- 150000001299 aldehydes Chemical class 0.000 description 29
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 27
- QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 26
- 239000012074 organic phase Substances 0.000 description 26
- 208000028867 ischemia Diseases 0.000 description 25
- 239000010410 layer Substances 0.000 description 25
- 239000002798 polar solvent Substances 0.000 description 25
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 24
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 23
- 230000002829 reductive effect Effects 0.000 description 23
- 150000001412 amines Chemical class 0.000 description 22
- RGHHSNMVTDWUBI-UHFFFAOYSA-N 4-hydroxybenzaldehyde Chemical class OC1=CC=C(C=O)C=C1 RGHHSNMVTDWUBI-UHFFFAOYSA-N 0.000 description 21
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 21
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 20
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 19
- FAMRKDQNMBBFBR-BQYQJAHWSA-N diethyl azodicarboxylate Substances CCOC(=O)\N=N\C(=O)OCC FAMRKDQNMBBFBR-BQYQJAHWSA-N 0.000 description 18
- FAMRKDQNMBBFBR-UHFFFAOYSA-N ethyl n-ethoxycarbonyliminocarbamate Chemical compound CCOC(=O)N=NC(=O)OCC FAMRKDQNMBBFBR-UHFFFAOYSA-N 0.000 description 18
- 235000017557 sodium bicarbonate Nutrition 0.000 description 18
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 18
- 239000005909 Kieselgur Substances 0.000 description 17
- 239000012279 sodium borohydride Substances 0.000 description 17
- 229910000033 sodium borohydride Inorganic materials 0.000 description 17
- 239000002253 acid Substances 0.000 description 16
- 239000000377 silicon dioxide Substances 0.000 description 16
- VXUYXOFXAQZZMF-UHFFFAOYSA-N titanium(IV) isopropoxide Chemical class CC(C)O[Ti](OC(C)C)(OC(C)C)OC(C)C VXUYXOFXAQZZMF-UHFFFAOYSA-N 0.000 description 16
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 description 15
- 239000008346 aqueous phase Substances 0.000 description 15
- 238000001914 filtration Methods 0.000 description 15
- 208000024827 Alzheimer disease Diseases 0.000 description 14
- 208000018737 Parkinson disease Diseases 0.000 description 14
- 239000012280 lithium aluminium hydride Substances 0.000 description 14
- 238000006268 reductive amination reaction Methods 0.000 description 14
- 238000010992 reflux Methods 0.000 description 14
- 239000000126 substance Substances 0.000 description 14
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 13
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 13
- 239000004480 active ingredient Substances 0.000 description 13
- 239000003638 chemical reducing agent Substances 0.000 description 13
- 238000005859 coupling reaction Methods 0.000 description 13
- 239000013078 crystal Substances 0.000 description 13
- 241000124008 Mammalia Species 0.000 description 12
- 229960000583 acetic acid Drugs 0.000 description 12
- 238000007792 addition Methods 0.000 description 12
- 229910021529 ammonia Inorganic materials 0.000 description 12
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 12
- 238000001816 cooling Methods 0.000 description 12
- 238000009472 formulation 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
- 125000006239 protecting group Chemical group 0.000 description 12
- 230000009467 reduction Effects 0.000 description 12
- 238000006722 reduction reaction Methods 0.000 description 12
- RMVRSNDYEFQCLF-UHFFFAOYSA-N thiophenol Chemical compound SC1=CC=CC=C1 RMVRSNDYEFQCLF-UHFFFAOYSA-N 0.000 description 12
- 239000003795 chemical substances by application Substances 0.000 description 11
- 230000008878 coupling Effects 0.000 description 11
- 238000010168 coupling process Methods 0.000 description 11
- 239000012043 crude product Substances 0.000 description 11
- 239000008367 deionised water Substances 0.000 description 11
- 229910021641 deionized water Inorganic materials 0.000 description 11
- 239000011261 inert gas Substances 0.000 description 11
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 10
- 238000006751 Mitsunobu reaction Methods 0.000 description 10
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 10
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 10
- WBHQBSYUUJJSRZ-UHFFFAOYSA-M sodium bisulfate Chemical compound [Na+].OS([O-])(=O)=O WBHQBSYUUJJSRZ-UHFFFAOYSA-M 0.000 description 10
- 239000012312 sodium hydride Substances 0.000 description 10
- 229910000104 sodium hydride Inorganic materials 0.000 description 10
- 239000007858 starting material Substances 0.000 description 10
- HJUGFYREWKUQJT-UHFFFAOYSA-N tetrabromomethane Chemical compound BrC(Br)(Br)Br HJUGFYREWKUQJT-UHFFFAOYSA-N 0.000 description 10
- 206010008120 Cerebral ischaemia Diseases 0.000 description 9
- 238000005481 NMR spectroscopy Methods 0.000 description 9
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 9
- 230000015572 biosynthetic process Effects 0.000 description 9
- 210000004556 brain Anatomy 0.000 description 9
- 150000001721 carbon Chemical group 0.000 description 9
- 201000010099 disease Diseases 0.000 description 9
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 9
- 238000010438 heat treatment Methods 0.000 description 9
- 238000002844 melting Methods 0.000 description 9
- 230000008018 melting Effects 0.000 description 9
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 9
- 239000002904 solvent Substances 0.000 description 9
- IMSODMZESSGVBE-UHFFFAOYSA-N 2-Oxazoline Chemical compound C1CN=CO1 IMSODMZESSGVBE-UHFFFAOYSA-N 0.000 description 8
- WPYMKLBDIGXBTP-UHFFFAOYSA-N Benzoic acid Natural products OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 8
- 201000006474 Brain Ischemia Diseases 0.000 description 8
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 8
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 8
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 8
- 241000700159 Rattus Species 0.000 description 8
- 239000002585 base Substances 0.000 description 8
- ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 description 8
- 206010008118 cerebral infarction Diseases 0.000 description 8
- 238000004587 chromatography analysis Methods 0.000 description 8
- 150000002148 esters Chemical class 0.000 description 8
- 239000012535 impurity Substances 0.000 description 8
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 8
- 230000004770 neurodegeneration Effects 0.000 description 8
- 229910052760 oxygen Inorganic materials 0.000 description 8
- 239000001301 oxygen Substances 0.000 description 8
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 8
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 8
- 150000003254 radicals Chemical class 0.000 description 8
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 8
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 7
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 7
- 238000001990 intravenous administration Methods 0.000 description 7
- 229910000342 sodium bisulfate Inorganic materials 0.000 description 7
- 239000005711 Benzoic acid Substances 0.000 description 6
- 201000010374 Down Syndrome Diseases 0.000 description 6
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 6
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 6
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 6
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 6
- 235000010233 benzoic acid Nutrition 0.000 description 6
- 150000001558 benzoic acid derivatives Chemical class 0.000 description 6
- 230000005779 cell damage Effects 0.000 description 6
- 208000037887 cell injury Diseases 0.000 description 6
- 230000006378 damage Effects 0.000 description 6
- 229940079593 drug Drugs 0.000 description 6
- 239000003814 drug Substances 0.000 description 6
- 150000004820 halides Chemical class 0.000 description 6
- 150000002500 ions Chemical class 0.000 description 6
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 6
- 239000011368 organic material Substances 0.000 description 6
- 229910000027 potassium carbonate Inorganic materials 0.000 description 6
- 239000000843 powder Substances 0.000 description 6
- 238000010898 silica gel chromatography Methods 0.000 description 6
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 6
- 239000007921 spray Substances 0.000 description 6
- 208000024891 symptom Diseases 0.000 description 6
- 238000012360 testing method Methods 0.000 description 6
- YPMDECDLDASBON-BQYQJAHWSA-N 4-[(E)-3-[2-(3,5-ditert-butyl-4-hydroxyphenyl)-1,3-oxazol-4-yl]prop-1-enyl]benzaldehyde Chemical compound CC(C)(C)C1=C(O)C(C(C)(C)C)=CC(C=2OC=C(C\C=C\C=3C=CC(C=O)=CC=3)N=2)=C1 YPMDECDLDASBON-BQYQJAHWSA-N 0.000 description 5
- 229920002472 Starch Polymers 0.000 description 5
- 208000006011 Stroke Diseases 0.000 description 5
- QIOZLISABUUKJY-UHFFFAOYSA-N Thiobenzamide Chemical compound NC(=S)C1=CC=CC=C1 QIOZLISABUUKJY-UHFFFAOYSA-N 0.000 description 5
- 206010044688 Trisomy 21 Diseases 0.000 description 5
- 230000001154 acute effect Effects 0.000 description 5
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 5
- HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 5
- 210000003169 central nervous system Anatomy 0.000 description 5
- OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 5
- JXMLAPZRDDWRRV-UHFFFAOYSA-N ethyl n-(ethoxycarbonylamino)carbamate Chemical compound CCOC(=O)NNC(=O)OCC JXMLAPZRDDWRRV-UHFFFAOYSA-N 0.000 description 5
- 239000007903 gelatin capsule Substances 0.000 description 5
- 230000007062 hydrolysis Effects 0.000 description 5
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- 150000004682 monohydrates Chemical class 0.000 description 5
- 210000000056 organ Anatomy 0.000 description 5
- 150000007524 organic acids Chemical class 0.000 description 5
- 150000003891 oxalate salts Chemical class 0.000 description 5
- 239000002244 precipitate Substances 0.000 description 5
- 150000003138 primary alcohols Chemical class 0.000 description 5
- 230000008569 process Effects 0.000 description 5
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- 239000003826 tablet Substances 0.000 description 5
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
- C07D263/52—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings condensed with carbocyclic rings or ring systems
- C07D263/54—Benzoxazoles; Hydrogenated benzoxazoles
- C07D263/56—Benzoxazoles; Hydrogenated benzoxazoles with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached in position 2
- C07D263/57—Aryl or substituted aryl radicals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/12—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/56—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
- C07D263/02—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings
- C07D263/08—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
- C07D263/10—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
- C07D263/14—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms with radicals substituted by oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
- C07D263/02—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings
- C07D263/30—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D263/32—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D271/00—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms
- C07D271/02—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms not condensed with other rings
- C07D271/06—1,2,4-Oxadiazoles; Hydrogenated 1,2,4-oxadiazoles
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
- C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D277/22—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
- C07D277/24—Radicals substituted by oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
- C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D277/22—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
- C07D277/26—Radicals substituted by sulfur atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Psychiatry (AREA)
- Hospice & Palliative Care (AREA)
- Psychology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Plural Heterocyclic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Liquid Crystal Substances (AREA)
- Adhesives Or Adhesive Processes (AREA)
- Saccharide Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (2)
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US2756096P | 1996-10-07 | 1996-10-07 | |
PCT/US1997/017963 WO1998015274A1 (en) | 1996-10-07 | 1997-10-06 | Novel compounds useful as neuro-protective agents |
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NO992226D0 NO992226D0 (no) | 1999-05-07 |
NO992226L NO992226L (no) | 1999-05-27 |
NO313193B1 true NO313193B1 (no) | 2002-08-26 |
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NO19992226A NO313193B1 (no) | 1996-10-07 | 1999-05-07 | Nye forbindelser for anvendelse som neuro-protektive midler |
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US (4) | US6156748A (pt) |
EP (1) | EP0971709B1 (pt) |
CN (1) | CN1239889A (pt) |
AT (1) | ATE240728T1 (pt) |
AU (1) | AU721355B2 (pt) |
CA (1) | CA2270661A1 (pt) |
CZ (1) | CZ166399A3 (pt) |
DE (1) | DE69722258T2 (pt) |
DK (1) | DK0971709T3 (pt) |
EA (1) | EA001713B1 (pt) |
ES (1) | ES2199353T3 (pt) |
HU (1) | HUP9904682A3 (pt) |
ID (1) | ID21472A (pt) |
IL (1) | IL129748A (pt) |
NO (1) | NO313193B1 (pt) |
NZ (1) | NZ335610A (pt) |
PT (1) | PT971709E (pt) |
TR (1) | TR199901559T2 (pt) |
WO (1) | WO1998015274A1 (pt) |
Families Citing this family (20)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5952360A (en) * | 1997-08-28 | 1999-09-14 | Eli Lilly And Company | Method for treating neuropathic pain |
US5942530A (en) * | 1997-08-28 | 1999-08-24 | Eli Lilly And Company | Method for treating pain |
CA2302294A1 (en) * | 1997-08-28 | 1999-03-04 | Harlan Edgar Shannon | Method for treating pain |
JP2001519341A (ja) * | 1997-10-06 | 2001-10-23 | イーライ・リリー・アンド・カンパニー | 神経保護剤として有用な新規化合物 |
IT1300055B1 (it) * | 1998-04-17 | 2000-04-05 | Boehringer Ingelheim Italia | Eterocicli con anello a 5 termini difenil-sostituiti loro procedimento di preparazione e loro impiego come farmici |
AU7315700A (en) | 1999-09-20 | 2001-04-24 | Takeda Chemical Industries Ltd. | Melanin concentrating hormone antagonist |
TWI283577B (en) * | 1999-10-11 | 2007-07-11 | Sod Conseils Rech Applic | Pharmaceutical composition of imidazole derivatives acting as modulators of sodium channels and the use thereof |
FR2812546B1 (fr) * | 2000-08-01 | 2008-11-21 | Sod Conseils Rech Applic | Derives d'heterocycles a 5 chainons, leur preparation et leur application a titre de medicaments |
DK1285651T3 (da) | 2000-04-28 | 2010-12-13 | Takeda Pharmaceutical | Melanin-koncentrerende hormon-antagonister |
CA2435820A1 (en) * | 2001-02-08 | 2002-08-15 | Karo Bio Ab | Phenoxy substituted benzocondensed heteroaryl derivatives as thyroid receptor ligands |
US7091357B2 (en) * | 2001-12-26 | 2006-08-15 | University Of Kentucky Research Foundation | Chain-modified pyridino-N substituted nicotine compounds for use in the treatment of CNS pathologies |
US7179808B2 (en) | 2002-07-03 | 2007-02-20 | Janssen Pharmaceutica N.V. | Substituted heteroaryl and heterocyclic compounds useful in treating inflammatory disorders |
EP3842055A1 (en) | 2003-02-04 | 2021-06-30 | Cornell Research Foundation, Inc. | Uses of aromatic-cationic peptide |
TW200505913A (en) | 2003-03-28 | 2005-02-16 | Hoffmann La Roche | Novel oxazole derivatives, their manufacture and use as pharmaceutical agents |
US7353897B2 (en) * | 2003-07-23 | 2008-04-08 | Fernandez Dennis S | Telematic method and apparatus with integrated power source |
US7550439B2 (en) | 2004-01-23 | 2009-06-23 | Cornell Research Foundation, Inc. | Methods for reducing oxidative damage |
JP5305914B2 (ja) | 2005-11-15 | 2013-10-02 | 大塚製薬株式会社 | オキサゾール化合物及び医薬組成物 |
EP2614549B1 (de) | 2010-09-06 | 2016-04-27 | Aigys AG | Betankbarer akku |
US10881162B2 (en) | 2015-05-07 | 2021-01-05 | Exero Labs LLC | Device for minimizing impact of collisions for a helmet |
WO2024040267A2 (en) * | 2022-08-19 | 2024-02-22 | Mitokinin, Inc. | Direct synthesis of n-(3-substituted-chroman-4-yl)-7h- pyrrolo[2,3-d]pyrimidin-4-amines and derivatives thereof |
Family Cites Families (15)
Publication number | Priority date | Publication date | Assignee | Title |
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US4636516A (en) * | 1981-02-19 | 1987-01-13 | Yamanouchi Pharmaceutical Co., Ltd. | 3,5-di-tert-butyl-4-hydroxyphenyl-substituted heterocyclic compounds |
DE3425118A1 (de) * | 1984-07-07 | 1986-01-16 | Boehringer Mannheim Gmbh, 6800 Mannheim | Neue redox-indikatoren |
GB8531608D0 (en) * | 1985-12-23 | 1986-02-05 | Beecham Group Plc | Treatment |
DE3621775A1 (de) * | 1986-03-13 | 1988-01-07 | Thomae Gmbh Dr K | Neue substituierte thiazole und oxazole, diese verbindungen enthaltende arzneimittel und verfahren zu ihrer herstellung |
CA2009470A1 (en) * | 1989-02-08 | 1990-08-08 | Yu Momose | Oxazole compounds and their use |
DE3903993A1 (de) * | 1989-02-10 | 1990-08-16 | Basf Ag | Diarylsubstituierte heterocyclische verbindungen, ihre herstellung und arzneimittel daraus |
DK0513379T3 (da) * | 1990-11-30 | 1996-09-30 | Teijin Ltd | 2-Arylthiazolderivater og farmaceutisk præparat indeholdende sådanne |
US5633271A (en) * | 1992-05-26 | 1997-05-27 | E. I. Du Pont De Nemours And Company | Arthropodicidal oxazolines and thiazolines |
DE4304197A1 (de) * | 1993-02-12 | 1994-08-18 | Bayer Ag | Substituierte Oxazole |
US5428048A (en) * | 1993-11-08 | 1995-06-27 | American Home Products Corporation | Aryl-N-hydroxyureas as inhibitors of 5-lipoxygenase and anto-arteriosclerotic agents |
US6251928B1 (en) * | 1994-03-16 | 2001-06-26 | Eli Lilly And Company | Treatment of alzheimer's disease employing inhibitors of cathepsin D |
US5952360A (en) * | 1997-08-28 | 1999-09-14 | Eli Lilly And Company | Method for treating neuropathic pain |
CA2302294A1 (en) * | 1997-08-28 | 1999-03-04 | Harlan Edgar Shannon | Method for treating pain |
US5942530A (en) * | 1997-08-28 | 1999-08-24 | Eli Lilly And Company | Method for treating pain |
JP2001519341A (ja) * | 1997-10-06 | 2001-10-23 | イーライ・リリー・アンド・カンパニー | 神経保護剤として有用な新規化合物 |
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1997
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- 1997-10-06 NZ NZ335610A patent/NZ335610A/xx unknown
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- 1997-10-06 EP EP97909975A patent/EP0971709B1/en not_active Expired - Lifetime
- 1997-10-06 AT AT97909975T patent/ATE240728T1/de not_active IP Right Cessation
- 1997-10-06 ID IDW990301A patent/ID21472A/id unknown
- 1997-10-06 PT PT97909975T patent/PT971709E/pt unknown
- 1997-10-06 TR TR1999/01559T patent/TR199901559T2/xx unknown
- 1997-10-06 AU AU47459/97A patent/AU721355B2/en not_active Ceased
- 1997-10-06 CN CN97180378A patent/CN1239889A/zh active Pending
- 1997-10-06 CZ CZ991663A patent/CZ166399A3/cs unknown
- 1997-10-06 CA CA002270661A patent/CA2270661A1/en not_active Abandoned
- 1997-10-06 IL IL12974897A patent/IL129748A/xx not_active IP Right Cessation
- 1997-10-06 EA EA199900362A patent/EA001713B1/ru not_active IP Right Cessation
- 1997-10-06 DE DE69722258T patent/DE69722258T2/de not_active Expired - Fee Related
- 1997-10-06 ES ES97909975T patent/ES2199353T3/es not_active Expired - Lifetime
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1999
- 1999-05-07 NO NO19992226A patent/NO313193B1/no not_active IP Right Cessation
- 1999-08-04 US US09/368,236 patent/US6166216A/en not_active Expired - Fee Related
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2000
- 2000-11-17 US US09/715,987 patent/US6380213B1/en not_active Expired - Fee Related
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2001
- 2001-11-28 US US09/996,005 patent/US6423709B1/en not_active Expired - Fee Related
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US6423709B1 (en) | 2002-07-23 |
IL129748A (en) | 2003-11-23 |
CA2270661A1 (en) | 1998-04-16 |
ID21472A (id) | 1999-06-17 |
WO1998015274A1 (en) | 1998-04-16 |
ES2199353T3 (es) | 2004-02-16 |
US6166216A (en) | 2000-12-26 |
DK0971709T3 (da) | 2003-09-22 |
EA001713B1 (ru) | 2001-08-27 |
NO992226D0 (no) | 1999-05-07 |
AU721355B2 (en) | 2000-06-29 |
EP0971709A4 (en) | 2001-04-11 |
HUP9904682A3 (en) | 2001-09-28 |
US20020065274A1 (en) | 2002-05-30 |
HUP9904682A2 (hu) | 2000-05-28 |
DE69722258D1 (de) | 2003-06-26 |
ATE240728T1 (de) | 2003-06-15 |
EP0971709B1 (en) | 2003-05-21 |
TR199901559T2 (xx) | 1999-09-21 |
EP0971709A1 (en) | 2000-01-19 |
DE69722258T2 (de) | 2004-03-18 |
AU4745997A (en) | 1998-05-05 |
CN1239889A (zh) | 1999-12-29 |
IL129748A0 (en) | 2000-02-29 |
PT971709E (pt) | 2003-09-30 |
US6156748A (en) | 2000-12-05 |
NO992226L (no) | 1999-05-27 |
EA199900362A1 (ru) | 2000-02-28 |
NZ335610A (en) | 2000-10-27 |
US6380213B1 (en) | 2002-04-30 |
CZ166399A3 (cs) | 1999-11-17 |
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