SK280268B6 - N-substituované 3,4-diamino-1,2-dioxo-3-cyklobutén - Google Patents
N-substituované 3,4-diamino-1,2-dioxo-3-cyklobutén Download PDFInfo
- Publication number
- SK280268B6 SK280268B6 SK144-92A SK14492A SK280268B6 SK 280268 B6 SK280268 B6 SK 280268B6 SK 14492 A SK14492 A SK 14492A SK 280268 B6 SK280268 B6 SK 280268B6
- Authority
- SK
- Slovakia
- Prior art keywords
- dioxo
- amino
- diamino
- substituted
- pharmaceutically acceptable
- Prior art date
Links
- -1 N-substituted 3,4-diamino-1,2-dioxo-3-cyclobutene Chemical class 0.000 title claims abstract description 89
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 42
- 150000003839 salts Chemical class 0.000 claims abstract description 37
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 31
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 30
- 239000001257 hydrogen Substances 0.000 claims abstract description 29
- 150000002431 hydrogen Chemical group 0.000 claims abstract description 17
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 10
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 8
- 125000003884 phenylalkyl group Chemical group 0.000 claims abstract description 8
- 125000003342 alkenyl group Chemical group 0.000 claims abstract description 5
- 125000002947 alkylene group Chemical group 0.000 claims abstract description 5
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 24
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 claims description 18
- 239000002253 acid Substances 0.000 claims description 15
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 15
- ABLZXFCXXLZCGV-UHFFFAOYSA-N Phosphorous acid Chemical compound OP(O)=O ABLZXFCXXLZCGV-UHFFFAOYSA-N 0.000 claims description 11
- 239000004471 Glycine Substances 0.000 claims description 9
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 8
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 7
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 5
- 230000002461 excitatory amino acid Effects 0.000 claims description 5
- 239000003257 excitatory amino acid Substances 0.000 claims description 5
- 206010010904 Convulsion Diseases 0.000 claims description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 4
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 4
- FNWQIMHBKBNCGJ-UHFFFAOYSA-N 2-(4-hydroxy-8,9-dioxo-2,6-diazabicyclo[5.2.0]non-1(7)-en-6-yl)ethylphosphonic acid Chemical compound OP(=O)(O)CCN1CC(O)CNC2=C1C(=O)C2=O FNWQIMHBKBNCGJ-UHFFFAOYSA-N 0.000 claims description 3
- OGJPVDOJIKYZDL-UHFFFAOYSA-N 2-(9,10-dioxo-2,7-diazabicyclo[6.2.0]dec-1(8)-en-7-yl)ethylphosphonic acid Chemical compound OP(O)(=O)CCN1CCCCNC2=C1C(=O)C2=O OGJPVDOJIKYZDL-UHFFFAOYSA-N 0.000 claims description 3
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 3
- BDABGOLMYNHHTR-UHFFFAOYSA-N Perzinfotel Chemical compound OP(O)(=O)CCN1CCCNC2=C1C(=O)C2=O BDABGOLMYNHHTR-UHFFFAOYSA-N 0.000 claims description 3
- QRIYUGMMSGNTDO-OWOJBTEDSA-N [(e)-4-[(2-amino-3,4-dioxocyclobuten-1-yl)amino]but-2-enyl]phosphonic acid Chemical compound NC1=C(NC\C=C\CP(O)(O)=O)C(=O)C1=O QRIYUGMMSGNTDO-OWOJBTEDSA-N 0.000 claims description 3
- 230000036461 convulsion Effects 0.000 claims description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 3
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 claims description 3
- 125000003161 (C1-C6) alkylene group Chemical group 0.000 claims description 2
- QPWUAYYTCGMJEU-UHFFFAOYSA-N 3-[[2-(benzylamino)-3,4-dioxocyclobuten-1-yl]amino]propanoic acid Chemical compound O=C1C(=O)C(NCCC(=O)O)=C1NCC1=CC=CC=C1 QPWUAYYTCGMJEU-UHFFFAOYSA-N 0.000 claims description 2
- GAJHFPYRNGGGFX-UHFFFAOYSA-N 4-[(2-amino-3,4-dioxocyclobuten-1-yl)amino]butanoic acid Chemical compound NC1=C(NCCCC(O)=O)C(=O)C1=O GAJHFPYRNGGGFX-UHFFFAOYSA-N 0.000 claims description 2
- VNKFCNIHRYMHHD-UHFFFAOYSA-N 6-[2-(2h-tetrazol-5-yl)ethyl]-2,6-diazabicyclo[5.2.0]non-1(7)-ene-8,9-dione Chemical compound C1=2C(=O)C(=O)C=2NCCCN1CCC1=NN=NN1 VNKFCNIHRYMHHD-UHFFFAOYSA-N 0.000 claims description 2
- 230000005779 cell damage Effects 0.000 claims description 2
- 208000037887 cell injury Diseases 0.000 claims description 2
- 125000005499 phosphonyl group Chemical group 0.000 claims description 2
- IBFIYYVNUZTZHQ-UHFFFAOYSA-N 2-[(2-amino-3,4-dioxocyclobuten-1-yl)-(2-methylprop-2-enyl)amino]acetic acid Chemical compound CC(=C)CN(CC(O)=O)C1=C(N)C(=O)C1=O IBFIYYVNUZTZHQ-UHFFFAOYSA-N 0.000 claims 1
- GWEBWKWCRBAAOJ-UHFFFAOYSA-N 2-[(2-amino-3,4-dioxocyclobuten-1-yl)-benzylamino]acetic acid Chemical compound O=C1C(=O)C(N)=C1N(CC(O)=O)CC1=CC=CC=C1 GWEBWKWCRBAAOJ-UHFFFAOYSA-N 0.000 claims 1
- GOJUJUVQIVIZAV-UHFFFAOYSA-N 2-amino-4,6-dichloropyrimidine-5-carbaldehyde Chemical group NC1=NC(Cl)=C(C=O)C(Cl)=N1 GOJUJUVQIVIZAV-UHFFFAOYSA-N 0.000 claims 1
- OMPJVKIOAHDOCP-UHFFFAOYSA-N 3-(8,9-dioxo-2,6-diazabicyclo[5.2.0]non-1(7)-en-6-yl)propylphosphonic acid Chemical compound OP(O)(=O)CCCN1CCCNC2=C1C(=O)C2=O OMPJVKIOAHDOCP-UHFFFAOYSA-N 0.000 claims 1
- KZRPOKATSDHKMF-UHFFFAOYSA-N 3-[(2-amino-3,4-dioxocyclobuten-1-yl)amino]propanoic acid Chemical compound NC1=C(NCCC(O)=O)C(=O)C1=O KZRPOKATSDHKMF-UHFFFAOYSA-N 0.000 claims 1
- HTQNQWWGIOTZGL-UHFFFAOYSA-N C(C(C1=C(C(=O)C1=O)N)N)P(=O)(O)O Chemical compound C(C(C1=C(C(=O)C1=O)N)N)P(=O)(O)O HTQNQWWGIOTZGL-UHFFFAOYSA-N 0.000 claims 1
- HQXDXUJFRXWLKX-UHFFFAOYSA-N C(CP(=O)(O)O)C(C1=C(C(=O)C1=O)N)N Chemical compound C(CP(=O)(O)O)C(C1=C(C(=O)C1=O)N)N HQXDXUJFRXWLKX-UHFFFAOYSA-N 0.000 claims 1
- HNENLYOKLDRBLV-UHFFFAOYSA-N C1(=C(C(=O)C1=O)N)C(N)P(=O)(O)O Chemical compound C1(=C(C(=O)C1=O)N)C(N)P(=O)(O)O HNENLYOKLDRBLV-UHFFFAOYSA-N 0.000 claims 1
- 102100035593 POU domain, class 2, transcription factor 1 Human genes 0.000 claims 1
- 101710084414 POU domain, class 2, transcription factor 1 Proteins 0.000 claims 1
- 235000004279 alanine Nutrition 0.000 claims 1
- 210000004958 brain cell Anatomy 0.000 claims 1
- IAQRGUVFOMOMEM-UHFFFAOYSA-N butene Natural products CC=CC IAQRGUVFOMOMEM-UHFFFAOYSA-N 0.000 claims 1
- 125000004494 ethyl ester group Chemical group 0.000 claims 1
- 230000002265 prevention Effects 0.000 claims 1
- 150000001875 compounds Chemical class 0.000 abstract description 60
- 125000004450 alkenylene group Chemical group 0.000 abstract description 4
- 239000004090 neuroprotective agent Substances 0.000 abstract 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 108
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 101
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 73
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 54
- 239000000243 solution Substances 0.000 description 52
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 51
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 40
- 239000007787 solid Substances 0.000 description 39
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 36
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 36
- 238000000921 elemental analysis Methods 0.000 description 34
- 238000000034 method Methods 0.000 description 34
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 33
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 32
- 229910001868 water Inorganic materials 0.000 description 29
- 229910052757 nitrogen Inorganic materials 0.000 description 27
- 239000011541 reaction mixture Substances 0.000 description 26
- 238000003818 flash chromatography Methods 0.000 description 22
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 20
- 239000003921 oil Substances 0.000 description 20
- 235000019198 oils Nutrition 0.000 description 20
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 18
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 16
- 239000000741 silica gel Substances 0.000 description 15
- 229910002027 silica gel Inorganic materials 0.000 description 15
- 238000010828 elution Methods 0.000 description 14
- 239000000203 mixture Substances 0.000 description 13
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 12
- 230000008569 process Effects 0.000 description 12
- 239000000376 reactant Substances 0.000 description 12
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 11
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 11
- 238000006243 chemical reaction Methods 0.000 description 11
- 239000000543 intermediate Substances 0.000 description 11
- 239000007788 liquid Substances 0.000 description 11
- 125000006239 protecting group Chemical group 0.000 description 11
- UCMIRNVEIXFBKS-UHFFFAOYSA-N beta-alanine Chemical compound NCCC(O)=O UCMIRNVEIXFBKS-UHFFFAOYSA-N 0.000 description 10
- IYYIVELXUANFED-UHFFFAOYSA-N bromo(trimethyl)silane Chemical compound C[Si](C)(C)Br IYYIVELXUANFED-UHFFFAOYSA-N 0.000 description 10
- 239000000725 suspension Substances 0.000 description 10
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 8
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 8
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 8
- 235000019253 formic acid Nutrition 0.000 description 8
- 239000000126 substance Substances 0.000 description 8
- KXDHJXZQYSOELW-UHFFFAOYSA-N carbonic acid monoamide Natural products NC(O)=O KXDHJXZQYSOELW-UHFFFAOYSA-N 0.000 description 7
- 150000002148 esters Chemical class 0.000 description 7
- 238000004992 fast atom bombardment mass spectroscopy Methods 0.000 description 7
- 239000003703 n methyl dextro aspartic acid receptor blocking agent Substances 0.000 description 7
- 238000002360 preparation method Methods 0.000 description 7
- 239000011734 sodium Substances 0.000 description 7
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 6
- DFSFLZCLKYZYRD-UHFFFAOYSA-N 3,4-diethoxycyclobut-3-ene-1,2-dione Chemical compound CCOC1=C(OCC)C(=O)C1=O DFSFLZCLKYZYRD-UHFFFAOYSA-N 0.000 description 6
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 6
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 6
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- 125000003545 alkoxy group Chemical group 0.000 description 6
- 239000000969 carrier Substances 0.000 description 6
- 238000010438 heat treatment Methods 0.000 description 6
- 239000010410 layer Substances 0.000 description 6
- 238000010992 reflux Methods 0.000 description 6
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 6
- KJAMZCVTJDTESW-UHFFFAOYSA-N tiracizine Chemical compound C1CC2=CC=CC=C2N(C(=O)CN(C)C)C2=CC(NC(=O)OCC)=CC=C21 KJAMZCVTJDTESW-UHFFFAOYSA-N 0.000 description 6
- 241000699670 Mus sp. Species 0.000 description 5
- 229940000635 beta-alanine Drugs 0.000 description 5
- 238000003776 cleavage reaction Methods 0.000 description 5
- 230000002860 competitive effect Effects 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- 239000012442 inert solvent Substances 0.000 description 5
- 231100000225 lethality Toxicity 0.000 description 5
- 239000000047 product Substances 0.000 description 5
- 230000007017 scission Effects 0.000 description 5
- 229910000104 sodium hydride Inorganic materials 0.000 description 5
- 159000000000 sodium salts Chemical class 0.000 description 5
- 208000024827 Alzheimer disease Diseases 0.000 description 4
- 229940099433 NMDA receptor antagonist Drugs 0.000 description 4
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
- 239000004480 active ingredient Substances 0.000 description 4
- 150000001412 amines Chemical class 0.000 description 4
- 239000002585 base Substances 0.000 description 4
- LDECUSDQMXVUMP-UHFFFAOYSA-N benzyl 3-[6-[[2-(butylamino)-1-[3-methoxycarbonyl-4-(2-methoxy-2-oxoethoxy)phenyl]-2-oxoethyl]-hexylamino]-6-oxohexyl]-4-methyl-2-oxo-6-(4-phenylphenyl)-1,6-dihydropyrimidine-5-carboxylate Chemical compound O=C1NC(C=2C=CC(=CC=2)C=2C=CC=CC=2)C(C(=O)OCC=2C=CC=CC=2)=C(C)N1CCCCCC(=O)N(CCCCCC)C(C(=O)NCCCC)C1=CC=C(OCC(=O)OC)C(C(=O)OC)=C1 LDECUSDQMXVUMP-UHFFFAOYSA-N 0.000 description 4
- 210000004556 brain Anatomy 0.000 description 4
- NEHMKBQYUWJMIP-UHFFFAOYSA-N chloromethane Chemical compound ClC NEHMKBQYUWJMIP-UHFFFAOYSA-N 0.000 description 4
- 150000004985 diamines Chemical class 0.000 description 4
- 238000006073 displacement reaction Methods 0.000 description 4
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 4
- 229910052736 halogen Inorganic materials 0.000 description 4
- 238000005984 hydrogenation reaction Methods 0.000 description 4
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 4
- 230000020477 pH reduction Effects 0.000 description 4
- 238000007363 ring formation reaction Methods 0.000 description 4
- 229910000029 sodium carbonate Inorganic materials 0.000 description 4
- 239000011780 sodium chloride Substances 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- XFNJVJPLKCPIBV-UHFFFAOYSA-N trimethylenediamine Chemical compound NCCCN XFNJVJPLKCPIBV-UHFFFAOYSA-N 0.000 description 4
- REXUYBKPWIPONM-UHFFFAOYSA-N 2-bromoacetonitrile Chemical compound BrCC#N REXUYBKPWIPONM-UHFFFAOYSA-N 0.000 description 3
- ZZWQVTBJLLXLPJ-UHFFFAOYSA-N 2-diethoxyphosphorylacetaldehyde Chemical compound CCOP(=O)(CC=O)OCC ZZWQVTBJLLXLPJ-UHFFFAOYSA-N 0.000 description 3
- RMMBULJTXVBMPL-UHFFFAOYSA-N 3-amino-4-ethoxycyclobut-3-ene-1,2-dione Chemical compound CCOC1=C(N)C(=O)C1=O RMMBULJTXVBMPL-UHFFFAOYSA-N 0.000 description 3
- 241000700159 Rattus Species 0.000 description 3
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 3
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 3
- 230000002378 acidificating effect Effects 0.000 description 3
- 229910052783 alkali metal Inorganic materials 0.000 description 3
- 229910021529 ammonia Inorganic materials 0.000 description 3
- 235000019270 ammonium chloride Nutrition 0.000 description 3
- 239000005557 antagonist Substances 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 3
- 206010008129 cerebral palsy Diseases 0.000 description 3
- 239000000460 chlorine Substances 0.000 description 3
- UVJHQYIOXKWHFD-UHFFFAOYSA-N cyclohexa-1,4-diene Chemical compound C1C=CCC=C1 UVJHQYIOXKWHFD-UHFFFAOYSA-N 0.000 description 3
- 239000003937 drug carrier Substances 0.000 description 3
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 3
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 3
- 239000012535 impurity Substances 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 238000002844 melting Methods 0.000 description 3
- 230000008018 melting Effects 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 239000012044 organic layer Substances 0.000 description 3
- 239000008194 pharmaceutical composition Substances 0.000 description 3
- 229920006395 saturated elastomer Polymers 0.000 description 3
- 239000012312 sodium hydride Substances 0.000 description 3
- 229910052938 sodium sulfate Inorganic materials 0.000 description 3
- 235000011152 sodium sulphate Nutrition 0.000 description 3
- 239000003381 stabilizer Substances 0.000 description 3
- 239000007858 starting material Substances 0.000 description 3
- 239000003826 tablet Substances 0.000 description 3
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 2
- PLRACCBDVIHHLZ-UHFFFAOYSA-N 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine Chemical compound C1N(C)CCC(C=2C=CC=CC=2)=C1 PLRACCBDVIHHLZ-UHFFFAOYSA-N 0.000 description 2
- PMJXRDNNUWCBAI-UHFFFAOYSA-N 2-(7,8-dioxo-2,5-diazabicyclo[4.2.0]oct-1(6)-en-5-yl)ethylphosphonic acid Chemical compound OP(O)(=O)CCN1CCNC2=C1C(=O)C2=O PMJXRDNNUWCBAI-UHFFFAOYSA-N 0.000 description 2
- XKOBFBCMSFVTSV-UHFFFAOYSA-N 2-(8,9-dioxo-2,6-diazabicyclo[5.2.0]non-1(7)-en-6-yl)acetic acid Chemical compound OC(=O)CN1CCCNC2=C1C(=O)C2=O XKOBFBCMSFVTSV-UHFFFAOYSA-N 0.000 description 2
- JVHNNQMJVXIGLG-UHFFFAOYSA-N 2-(8,9-dioxo-2,6-diazabicyclo[5.2.0]non-1(7)-en-6-yl)acetonitrile Chemical compound N1CCCN(CC#N)C2=C1C(=O)C2=O JVHNNQMJVXIGLG-UHFFFAOYSA-N 0.000 description 2
- XIVLBUFFTNVFGO-UHFFFAOYSA-N 2-[(2-ethoxy-3,4-dioxocyclobuten-1-yl)amino]ethylphosphonic acid Chemical compound CCOC1=C(NCCP(O)(O)=O)C(=O)C1=O XIVLBUFFTNVFGO-UHFFFAOYSA-N 0.000 description 2
- IPVBVKJFAICVEV-UHFFFAOYSA-N 3-amino-4-(2-diethoxyphosphorylethylamino)cyclobut-3-ene-1,2-dione Chemical compound CCOP(=O)(OCC)CCNC1=C(N)C(=O)C1=O IPVBVKJFAICVEV-UHFFFAOYSA-N 0.000 description 2
- VOROEQBFPPIACJ-UHFFFAOYSA-N 5-Phosphononorvaline Chemical group OC(=O)C(N)CCCP(O)(O)=O VOROEQBFPPIACJ-UHFFFAOYSA-N 0.000 description 2
- MPTBIGGYGATXPP-UHFFFAOYSA-N 6-(2h-tetrazol-5-ylmethyl)-2,6-diazabicyclo[5.2.0]non-1(7)-ene-8,9-dione Chemical compound C1=2C(=O)C(=O)C=2NCCCN1CC1=NN=NN1 MPTBIGGYGATXPP-UHFFFAOYSA-N 0.000 description 2
- VVJKKWFAADXIJK-UHFFFAOYSA-N Allylamine Chemical compound NCC=C VVJKKWFAADXIJK-UHFFFAOYSA-N 0.000 description 2
- FRPHFZCDPYBUAU-UHFFFAOYSA-N Bromocresolgreen Chemical compound CC1=C(Br)C(O)=C(Br)C=C1C1(C=2C(=C(Br)C(O)=C(Br)C=2)C)C2=CC=CC=C2S(=O)(=O)O1 FRPHFZCDPYBUAU-UHFFFAOYSA-N 0.000 description 2
- 102000018899 Glutamate Receptors Human genes 0.000 description 2
- 108010027915 Glutamate Receptors Proteins 0.000 description 2
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 2
- 208000002033 Myoclonus Diseases 0.000 description 2
- 102000004868 N-Methyl-D-Aspartate Receptors Human genes 0.000 description 2
- 108090001041 N-Methyl-D-Aspartate Receptors Proteins 0.000 description 2
- LPMRCCNDNGONCD-RITPCOANSA-N Selfotel Chemical compound OC(=O)[C@@H]1C[C@H](CP(O)(O)=O)CCN1 LPMRCCNDNGONCD-RITPCOANSA-N 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- 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 2
- 239000000654 additive Substances 0.000 description 2
- 239000000556 agonist Substances 0.000 description 2
- 125000005263 alkylenediamine group Chemical group 0.000 description 2
- 235000001014 amino acid Nutrition 0.000 description 2
- 150000001413 amino acids Chemical class 0.000 description 2
- 230000001773 anti-convulsant effect Effects 0.000 description 2
- 239000001961 anticonvulsive agent Substances 0.000 description 2
- 229960003965 antiepileptics Drugs 0.000 description 2
- 150000001540 azides Chemical class 0.000 description 2
- JXWABCYGGVHAHB-UHFFFAOYSA-N benzyl n-(3-aminopropyl)carbamate Chemical compound NCCCNC(=O)OCC1=CC=CC=C1 JXWABCYGGVHAHB-UHFFFAOYSA-N 0.000 description 2
- WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 2
- 238000009835 boiling Methods 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 239000001768 carboxy methyl cellulose Substances 0.000 description 2
- 239000001913 cellulose Substances 0.000 description 2
- 229920002678 cellulose Polymers 0.000 description 2
- 235000010980 cellulose Nutrition 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 239000012230 colorless oil Substances 0.000 description 2
- 239000006071 cream Substances 0.000 description 2
- UIBCDEFKKLRXHR-UHFFFAOYSA-N diethoxyphosphorylmethanamine Chemical compound CCOP(=O)(CN)OCC UIBCDEFKKLRXHR-UHFFFAOYSA-N 0.000 description 2
- MJUJXFBTEFXVKU-UHFFFAOYSA-N diethyl phosphonate Chemical compound CCOP(=O)OCC MJUJXFBTEFXVKU-UHFFFAOYSA-N 0.000 description 2
- 208000035475 disorder Diseases 0.000 description 2
- 206010015037 epilepsy Diseases 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 239000000796 flavoring agent Substances 0.000 description 2
- 235000013355 food flavoring agent Nutrition 0.000 description 2
- BTCSSZJGUNDROE-UHFFFAOYSA-N gamma-aminobutyric acid Chemical compound NCCCC(O)=O BTCSSZJGUNDROE-UHFFFAOYSA-N 0.000 description 2
- 150000002367 halogens Chemical class 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 238000007918 intramuscular administration Methods 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 238000007911 parenteral administration Methods 0.000 description 2
- 239000003208 petroleum Substances 0.000 description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 2
- 150000003008 phosphonic acid esters Chemical class 0.000 description 2
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- KIDHWZJUCRJVML-UHFFFAOYSA-N putrescine Chemical compound NCCCCN KIDHWZJUCRJVML-UHFFFAOYSA-N 0.000 description 2
- 238000001953 recrystallisation Methods 0.000 description 2
- 239000011347 resin Substances 0.000 description 2
- 229920005989 resin Polymers 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 2
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 2
- 239000008174 sterile solution Substances 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 125000001424 substituent group Chemical group 0.000 description 2
- DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 2
- ADGRBGALEZJKLW-UHFFFAOYSA-N tert-butyl 2-[3-(phenylmethoxycarbonylamino)propylamino]acetate Chemical compound CC(C)(C)OC(=O)CNCCCNC(=O)OCC1=CC=CC=C1 ADGRBGALEZJKLW-UHFFFAOYSA-N 0.000 description 2
- BNWCETAHAJSBFG-UHFFFAOYSA-N tert-butyl 2-bromoacetate Chemical compound CC(C)(C)OC(=O)CBr BNWCETAHAJSBFG-UHFFFAOYSA-N 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- 238000001149 thermolysis Methods 0.000 description 2
- 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 description 1
- LQUUQSXLRNIFCZ-UHFFFAOYSA-N (3-amino-2-hydroxypropyl)carbamic acid Chemical compound NCC(O)CNC(O)=O LQUUQSXLRNIFCZ-UHFFFAOYSA-N 0.000 description 1
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 description 1
- 125000004747 1,1-dimethylethoxycarbonyl group Chemical group CC(C)(OC(=O)*)C 0.000 description 1
- UYBWIEGTWASWSR-UHFFFAOYSA-N 1,3-diaminopropan-2-ol Chemical compound NCC(O)CN UYBWIEGTWASWSR-UHFFFAOYSA-N 0.000 description 1
- UIWJXEAMDJCNOV-UHFFFAOYSA-N 1-chloro-3-(chloromethyl)-2,4,5,6-tetrafluorobenzene Chemical compound FC1=C(F)C(Cl)=C(F)C(CCl)=C1F UIWJXEAMDJCNOV-UHFFFAOYSA-N 0.000 description 1
- DDHUNHGZUHZNKB-UHFFFAOYSA-N 2,2-dimethylpropane-1,3-diamine Chemical compound NCC(C)(C)CN DDHUNHGZUHZNKB-UHFFFAOYSA-N 0.000 description 1
- PZAQPYHHNBREAK-UHFFFAOYSA-N 2-(2-aminoethyl)-1,2,4-oxadiazolidine-3,5-dione;hydrobromide Chemical compound Br.NCCN1OC(=O)NC1=O PZAQPYHHNBREAK-UHFFFAOYSA-N 0.000 description 1
- XFAHIODKMNWZPL-UHFFFAOYSA-N 2-[(2-amino-3,4-dioxocyclobuten-1-yl)amino]ethylphosphonic acid Chemical compound NC1=C(NCCP(O)(O)=O)C(=O)C1=O XFAHIODKMNWZPL-UHFFFAOYSA-N 0.000 description 1
- SHNYINLDBGADJX-UHFFFAOYSA-N 2-[(2-amino-3,4-dioxocyclobuten-1-yl)methylamino]ethylphosphonic acid Chemical compound NC1=C(CNCCP(O)(O)=O)C(=O)C1=O SHNYINLDBGADJX-UHFFFAOYSA-N 0.000 description 1
- JUAGHBASZWRMQH-UHFFFAOYSA-N 2-diethoxyphosphorylethanamine Chemical compound CCOP(=O)(CCN)OCC JUAGHBASZWRMQH-UHFFFAOYSA-N 0.000 description 1
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 1
- WUACDRFRFTWMHE-UHFFFAOYSA-N 3,4-diaminocyclobut-3-ene-1,2-dione Chemical class NC1=C(N)C(=O)C1=O WUACDRFRFTWMHE-UHFFFAOYSA-N 0.000 description 1
- SZBNZTGCAMLMJY-UHFFFAOYSA-N 3,4-dimethoxycyclobut-3-ene-1,2-dione Chemical compound COC1=C(OC)C(=O)C1=O SZBNZTGCAMLMJY-UHFFFAOYSA-N 0.000 description 1
- QELVHTZDQKSPEL-UHFFFAOYSA-N 3-(7,8-dioxo-2,5-diazabicyclo[4.2.0]oct-1(6)-en-5-yl)propylphosphonic acid Chemical compound OP(O)(=O)CCCN1CCNC2=C1C(=O)C2=O QELVHTZDQKSPEL-UHFFFAOYSA-N 0.000 description 1
- JFBJJNQPIJHMPP-UHFFFAOYSA-N 3-(benzylamino)-4-ethoxycyclobut-3-ene-1,2-dione Chemical compound O=C1C(=O)C(OCC)=C1NCC1=CC=CC=C1 JFBJJNQPIJHMPP-UHFFFAOYSA-N 0.000 description 1
- RARPYAVALSABGF-UHFFFAOYSA-N 3-[(2-amino-3,4-dioxocyclobuten-1-yl)amino]propylphosphonic acid Chemical compound NC1=C(NCCCP(O)(O)=O)C(=O)C1=O RARPYAVALSABGF-UHFFFAOYSA-N 0.000 description 1
- OGKXBHGZDAPOKD-UHFFFAOYSA-N 3-[(2-diethoxyphosphorylethylamino)methyl]-4-ethoxycyclobut-3-ene-1,2-dione Chemical compound CCOC1=C(CNCCP(=O)(OCC)OCC)C(=O)C1=O OGKXBHGZDAPOKD-UHFFFAOYSA-N 0.000 description 1
- AEIKKZPUHUCEBZ-BQYQJAHWSA-N 3-[[(e)-4-diethoxyphosphorylbut-2-enyl]amino]-4-ethoxycyclobut-3-ene-1,2-dione Chemical compound CCOC1=C(NC\C=C\CP(=O)(OCC)OCC)C(=O)C1=O AEIKKZPUHUCEBZ-BQYQJAHWSA-N 0.000 description 1
- SLERNZQPROEOSU-UHFFFAOYSA-N 3-[cyanomethyl-(2-ethoxy-3,4-dioxocyclobuten-1-yl)amino]propylcarbamic acid Chemical compound CCOC1=C(N(CCCNC(O)=O)CC#N)C(=O)C1=O SLERNZQPROEOSU-UHFFFAOYSA-N 0.000 description 1
- ALBDIZITHLSSHU-AATRIKPKSA-N 3-amino-4-[[(e)-4-diethoxyphosphorylbut-2-enyl]amino]cyclobut-3-ene-1,2-dione Chemical compound CCOP(=O)(OCC)C\C=C\CNC1=C(N)C(=O)C1=O ALBDIZITHLSSHU-AATRIKPKSA-N 0.000 description 1
- DTCQVCMXPVEYCT-UHFFFAOYSA-N 3-aminocyclobut-3-ene-1,2-dione Chemical compound NC1=CC(=O)C1=O DTCQVCMXPVEYCT-UHFFFAOYSA-N 0.000 description 1
- CQZIEDXCLQOOEH-UHFFFAOYSA-N 3-bromopropanenitrile Chemical compound BrCCC#N CQZIEDXCLQOOEH-UHFFFAOYSA-N 0.000 description 1
- DQORFBNFNLHVIM-UHFFFAOYSA-N 3-diethoxyphosphorylpropan-1-amine Chemical compound CCOP(=O)(OCC)CCCN DQORFBNFNLHVIM-UHFFFAOYSA-N 0.000 description 1
- TVUDBAYBOZLIOU-UHFFFAOYSA-N 3-ethoxy-4-(methylamino)cyclobut-3-ene-1,2-dione Chemical compound CCOC1=C(NC)C(=O)C1=O TVUDBAYBOZLIOU-UHFFFAOYSA-N 0.000 description 1
- NCTHGNMZDQNCKX-UHFFFAOYSA-N 3-ethoxy-4-(prop-2-enylamino)cyclobut-3-ene-1,2-dione Chemical compound CCOC1=C(NCC=C)C(=O)C1=O NCTHGNMZDQNCKX-UHFFFAOYSA-N 0.000 description 1
- 125000006201 3-phenylpropyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- JDFGVBVRUPCWDZ-UHFFFAOYSA-N 4-(2-diethoxyphosphorylethylamino)butylcarbamic acid Chemical compound CCOP(=O)(OCC)CCNCCCCNC(O)=O JDFGVBVRUPCWDZ-UHFFFAOYSA-N 0.000 description 1
- CUVGUPIVTLGRGI-UHFFFAOYSA-N 4-(3-phosphonopropyl)piperazine-2-carboxylic acid Chemical compound OC(=O)C1CN(CCCP(O)(O)=O)CCN1 CUVGUPIVTLGRGI-UHFFFAOYSA-N 0.000 description 1
- WGPZNNKPLJPQAL-UHFFFAOYSA-N 4-aminobutylcarbamic acid Chemical compound NCCCCNC(O)=O WGPZNNKPLJPQAL-UHFFFAOYSA-N 0.000 description 1
- ABGYRKSUMIOZDY-UHFFFAOYSA-N 4-diethoxyphosphorylbutan-1-amine Chemical compound CCOP(=O)(OCC)CCCCN ABGYRKSUMIOZDY-UHFFFAOYSA-N 0.000 description 1
- HIQIXEFWDLTDED-UHFFFAOYSA-N 4-hydroxy-1-piperidin-4-ylpyrrolidin-2-one Chemical compound O=C1CC(O)CN1C1CCNCC1 HIQIXEFWDLTDED-UHFFFAOYSA-N 0.000 description 1
- WAYCHUDVDVEWOZ-UHFFFAOYSA-N 5-(2-diethoxyphosphorylethyl)-2,5-diazabicyclo[4.2.0]oct-1(6)-ene-7,8-dione Chemical compound CCOP(=O)(OCC)CCN1CCNC2=C1C(=O)C2=O WAYCHUDVDVEWOZ-UHFFFAOYSA-N 0.000 description 1
- IJIBRSFAXRFPPN-UHFFFAOYSA-N 5-bromo-2-methoxybenzaldehyde Chemical compound COC1=CC=C(Br)C=C1C=O IJIBRSFAXRFPPN-UHFFFAOYSA-N 0.000 description 1
- RMZDUZKPZCCPNF-UHFFFAOYSA-N 6-(2-diethoxyphosphorylethyl)-2,6-diazabicyclo[5.2.0]non-1(7)-ene-8,9-dione Chemical compound CCOP(=O)(OCC)CCN1CCCNC2=C1C(=O)C2=O RMZDUZKPZCCPNF-UHFFFAOYSA-N 0.000 description 1
- IVHNXDDWDZCRLX-UHFFFAOYSA-N 6-(2-diethoxyphosphorylethyl)-4-hydroxy-2,6-diazabicyclo[5.2.0]non-1(7)-ene-8,9-dione Chemical compound CCOP(=O)(OCC)CCN1CC(O)CNC2=C1C(=O)C2=O IVHNXDDWDZCRLX-UHFFFAOYSA-N 0.000 description 1
- MPNMRZXQXOTTPZ-UHFFFAOYSA-N 7-(2-diethoxyphosphorylethyl)-2,7-diazabicyclo[6.2.0]dec-1(8)-ene-9,10-dione Chemical compound CCOP(=O)(OCC)CCN1CCCCNC2=C1C(=O)C2=O MPNMRZXQXOTTPZ-UHFFFAOYSA-N 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- 201000006474 Brain Ischemia Diseases 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 206010008120 Cerebral ischaemia Diseases 0.000 description 1
- 206010008190 Cerebrovascular accident Diseases 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- 235000013162 Cocos nucifera Nutrition 0.000 description 1
- 244000060011 Cocos nucifera Species 0.000 description 1
- 229920001353 Dextrin Polymers 0.000 description 1
- 239000004375 Dextrin Substances 0.000 description 1
- LVGKNOAMLMIIKO-UHFFFAOYSA-N Elaidinsaeure-aethylester Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC LVGKNOAMLMIIKO-UHFFFAOYSA-N 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 241000699694 Gerbillinae Species 0.000 description 1
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 1
- 208000023105 Huntington disease Diseases 0.000 description 1
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical class OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 1
- 208000013016 Hypoglycemia Diseases 0.000 description 1
- 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 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 101001135571 Mus musculus Tyrosine-protein phosphatase non-receptor type 2 Proteins 0.000 description 1
- 238000007126 N-alkylation reaction Methods 0.000 description 1
- 229940127523 NMDA Receptor Antagonists Drugs 0.000 description 1
- QWZRZYWLWTWVLF-UHFFFAOYSA-N O.OP(O)=O Chemical compound O.OP(O)=O QWZRZYWLWTWVLF-UHFFFAOYSA-N 0.000 description 1
- 208000018737 Parkinson disease Diseases 0.000 description 1
- 235000019483 Peanut oil Nutrition 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 239000005700 Putrescine Substances 0.000 description 1
- 206010039966 Senile dementia Diseases 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 208000006011 Stroke Diseases 0.000 description 1
- 241000906446 Theraps Species 0.000 description 1
- OKJPEAGHQZHRQV-UHFFFAOYSA-N Triiodomethane Natural products IC(I)I OKJPEAGHQZHRQV-UHFFFAOYSA-N 0.000 description 1
- BTBQNZRXIUBLBR-UHFFFAOYSA-N [(2-amino-3,4-dioxocyclobuten-1-yl)amino]methylphosphonic acid Chemical compound NC1=C(NCP(O)(O)=O)C(=O)C1=O BTBQNZRXIUBLBR-UHFFFAOYSA-N 0.000 description 1
- TWQTWWHLTVYYNM-ONEGZZNKSA-N [(E)-4-[(2-ethoxy-3,4-dioxocyclobuten-1-yl)amino]but-2-enyl]phosphonic acid Chemical compound CCOC1=C(NC\C=C\CP(O)(O)=O)C(=O)C1=O TWQTWWHLTVYYNM-ONEGZZNKSA-N 0.000 description 1
- FSBLWNPHZVUVQW-ORCRQEGFSA-N [(e)-3-(7,8-dioxo-2,5-diazabicyclo[4.2.0]oct-1(6)-en-5-yl)prop-1-enyl]phosphonic acid Chemical compound OP(O)(=O)\C=C\CN1CCNC2=C1C(=O)C2=O FSBLWNPHZVUVQW-ORCRQEGFSA-N 0.000 description 1
- DVAAQXSKOCTQJE-UHFFFAOYSA-N [N]C(=O)CC1=CC=CC=C1 Chemical group [N]C(=O)CC1=CC=CC=C1 DVAAQXSKOCTQJE-UHFFFAOYSA-N 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 125000002252 acyl group Chemical group 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 150000008044 alkali metal hydroxides Chemical class 0.000 description 1
- 150000001340 alkali metals Chemical class 0.000 description 1
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
- 150000001342 alkaline earth metals Chemical class 0.000 description 1
- 125000005907 alkyl ester group Chemical group 0.000 description 1
- 150000001350 alkyl halides Chemical class 0.000 description 1
- VREFGVBLTWBCJP-UHFFFAOYSA-N alprazolam Chemical compound C12=CC(Cl)=CC=C2N2C(C)=NN=C2CN=C1C1=CC=CC=C1 VREFGVBLTWBCJP-UHFFFAOYSA-N 0.000 description 1
- 125000006242 amine protecting group Chemical group 0.000 description 1
- 239000000908 ammonium hydroxide Substances 0.000 description 1
- 150000003863 ammonium salts Chemical class 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 150000001450 anions Chemical class 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 238000011914 asymmetric synthesis Methods 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- ZXVOCOLRQJZVBW-UHFFFAOYSA-N azane;ethanol Chemical compound N.CCO ZXVOCOLRQJZVBW-UHFFFAOYSA-N 0.000 description 1
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 1
- QMMFTRJQCCVPCE-UHFFFAOYSA-N benzyl n-(2-aminoethyl)carbamate Chemical compound NCCNC(=O)OCC1=CC=CC=C1 QMMFTRJQCCVPCE-UHFFFAOYSA-N 0.000 description 1
- RMYDGHAHPRQOSN-UHFFFAOYSA-N benzyl n-[2-(2-diethoxyphosphorylethylamino)ethyl]carbamate Chemical compound CCOP(=O)(OCC)CCNCCNC(=O)OCC1=CC=CC=C1 RMYDGHAHPRQOSN-UHFFFAOYSA-N 0.000 description 1
- BUIFSMIGIDBJRN-UHFFFAOYSA-N benzyl n-[3-(2-diethoxyphosphorylethylamino)propyl]carbamate Chemical compound CCOP(=O)(OCC)CCNCCCNC(=O)OCC1=CC=CC=C1 BUIFSMIGIDBJRN-UHFFFAOYSA-N 0.000 description 1
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 description 1
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 1
- 125000002619 bicyclic group Chemical group 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 208000029028 brain injury Diseases 0.000 description 1
- 239000012267 brine Substances 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical group 0.000 description 1
- 125000002091 cationic group Chemical group 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 208000015114 central nervous system disease Diseases 0.000 description 1
- 230000002490 cerebral effect Effects 0.000 description 1
- 206010008118 cerebral infarction Diseases 0.000 description 1
- 150000005829 chemical entities Chemical class 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 230000006835 compression Effects 0.000 description 1
- 238000007906 compression Methods 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 239000013058 crude material Substances 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- RGBVWCQARBEPPW-UHFFFAOYSA-N cyclobut-3-ene-1,2-dione Chemical compound O=C1C=CC1=O RGBVWCQARBEPPW-UHFFFAOYSA-N 0.000 description 1
- 101150047356 dec-1 gene Proteins 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 230000003412 degenerative effect Effects 0.000 description 1
- 239000008367 deionised water Substances 0.000 description 1
- 229910021641 deionized water Inorganic materials 0.000 description 1
- 230000002542 deteriorative effect Effects 0.000 description 1
- 235000019425 dextrin Nutrition 0.000 description 1
- 125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 230000004064 dysfunction Effects 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 230000001856 erectile effect Effects 0.000 description 1
- NTNZTEQNFHNYBC-UHFFFAOYSA-N ethyl 2-aminoacetate Chemical compound CCOC(=O)CN NTNZTEQNFHNYBC-UHFFFAOYSA-N 0.000 description 1
- FQTIYMRSUOADDK-UHFFFAOYSA-N ethyl 3-bromopropanoate Chemical compound CCOC(=O)CCBr FQTIYMRSUOADDK-UHFFFAOYSA-N 0.000 description 1
- MHYCRLGKOZWVEF-UHFFFAOYSA-N ethyl acetate;hydrate Chemical compound O.CCOC(C)=O MHYCRLGKOZWVEF-UHFFFAOYSA-N 0.000 description 1
- LVGKNOAMLMIIKO-QXMHVHEDSA-N ethyl oleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC LVGKNOAMLMIIKO-QXMHVHEDSA-N 0.000 description 1
- 229940093471 ethyl oleate Drugs 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 239000006260 foam Substances 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 229960003692 gamma aminobutyric acid Drugs 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 229930195712 glutamate Natural products 0.000 description 1
- 235000013922 glutamic acid Nutrition 0.000 description 1
- 239000004220 glutamic acid Substances 0.000 description 1
- 150000002334 glycols Chemical class 0.000 description 1
- 150000008282 halocarbons Chemical class 0.000 description 1
- 210000002837 heart atrium Anatomy 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 230000002218 hypoglycaemic effect Effects 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 239000007927 intramuscular injection Substances 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 239000007928 intraperitoneal injection Substances 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
- 238000005342 ion exchange Methods 0.000 description 1
- 230000000302 ischemic effect Effects 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 210000003141 lower extremity Anatomy 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 238000010907 mechanical stirring Methods 0.000 description 1
- 230000006993 memory improvement Effects 0.000 description 1
- 125000005394 methallyl group Chemical group 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 230000004770 neurodegeneration Effects 0.000 description 1
- 208000015122 neurodegenerative disease Diseases 0.000 description 1
- 210000002569 neuron Anatomy 0.000 description 1
- 230000003961 neuronal insult Effects 0.000 description 1
- 230000000324 neuroprotective effect Effects 0.000 description 1
- 239000002858 neurotransmitter agent Substances 0.000 description 1
- 150000002825 nitriles Chemical class 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- 235000014593 oils and fats Nutrition 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000012057 packaged powder Substances 0.000 description 1
- 239000005022 packaging material Substances 0.000 description 1
- 239000011236 particulate material Substances 0.000 description 1
- 239000000312 peanut oil Substances 0.000 description 1
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 150000003254 radicals Chemical class 0.000 description 1
- 230000002285 radioactive effect Effects 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000011514 reflex Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- DCKVNWZUADLDEH-UHFFFAOYSA-N sec-butyl acetate Chemical compound CCC(C)OC(C)=O DCKVNWZUADLDEH-UHFFFAOYSA-N 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- VFEOWKQAEKOENB-UHFFFAOYSA-M sodium 2-(8,9-dioxo-2,6-diazabicyclo[5.2.0]non-1(7)-en-2-yl)acetate hydrate Chemical compound O.[Na+].[O-]C(=O)CN1CCCNc2c1c(=O)c2=O VFEOWKQAEKOENB-UHFFFAOYSA-M 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
- 210000000278 spinal cord Anatomy 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000007885 tablet disintegrant Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- ZGHWMZQPSBAQAU-UHFFFAOYSA-N tert-butyl 2-[(2-amino-3,4-dioxocyclobuten-1-yl)-prop-2-enylamino]acetate Chemical compound CC(C)(C)OC(=O)CN(CC=C)C1=C(N)C(=O)C1=O ZGHWMZQPSBAQAU-UHFFFAOYSA-N 0.000 description 1
- SJMDMGHPMLKLHQ-UHFFFAOYSA-N tert-butyl 2-aminoacetate Chemical compound CC(C)(C)OC(=O)CN SJMDMGHPMLKLHQ-UHFFFAOYSA-N 0.000 description 1
- LFKDJXLFVYVEFG-UHFFFAOYSA-N tert-butyl carbamate Chemical compound CC(C)(C)OC(N)=O LFKDJXLFVYVEFG-UHFFFAOYSA-N 0.000 description 1
- LZNOKWJGNPKUSE-UHFFFAOYSA-N tert-butyl n-(3-amino-2-hydroxypropyl)carbamate Chemical compound CC(C)(C)OC(=O)NCC(O)CN LZNOKWJGNPKUSE-UHFFFAOYSA-N 0.000 description 1
- POHWAQLZBIMPRN-UHFFFAOYSA-N tert-butyl n-(3-aminopropyl)carbamate Chemical compound CC(C)(C)OC(=O)NCCCN POHWAQLZBIMPRN-UHFFFAOYSA-N 0.000 description 1
- ZFQWJXFJJZUVPI-UHFFFAOYSA-N tert-butyl n-(4-aminobutyl)carbamate Chemical compound CC(C)(C)OC(=O)NCCCCN ZFQWJXFJJZUVPI-UHFFFAOYSA-N 0.000 description 1
- QLFITVRIMCNYPK-UHFFFAOYSA-N tert-butyl n-[3-[cyanomethyl-(2-ethoxy-3,4-dioxocyclobuten-1-yl)amino]propyl]carbamate Chemical compound CCOC1=C(N(CCCNC(=O)OC(C)(C)C)CC#N)C(=O)C1=O QLFITVRIMCNYPK-UHFFFAOYSA-N 0.000 description 1
- 150000003536 tetrazoles Chemical class 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 125000003944 tolyl group Chemical group 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
- 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
- 238000005303 weighing Methods 0.000 description 1
Classifications
-
- 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
- C07D271/07—1,2,4-Oxadiazoles; Hydrogenated 1,2,4-oxadiazoles with oxygen, sulfur or nitrogen atoms, directly attached to ring carbon atoms, the nitrogen atoms not forming part of a nitro radical
-
- 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
-
- 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
-
- 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
- A61P25/08—Antiepileptics; Anticonvulsants
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- 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
- C07C229/10—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 acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings
- C07C229/16—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 acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings to carbon atoms of hydrocarbon radicals substituted by amino or carboxyl groups, e.g. ethylenediamine-tetra-acetic acid, iminodiacetic acids
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D243/00—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms
- C07D243/06—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms having the nitrogen atoms in positions 1 and 4
- C07D243/10—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms having the nitrogen atoms in positions 1 and 4 condensed with carbocyclic rings or ring systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/28—Phosphorus compounds with one or more P—C bonds
- C07F9/38—Phosphonic acids [RP(=O)(OH)2]; Thiophosphonic acids ; [RP(=X1)(X2H)2(X1, X2 are each independently O, S or Se)]
- C07F9/3804—Phosphonic acids [RP(=O)(OH)2]; Thiophosphonic acids ; [RP(=X1)(X2H)2(X1, X2 are each independently O, S or Se)] not used, see subgroups
- C07F9/3808—Acyclic saturated acids which can have further substituents on alkyl
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/28—Phosphorus compounds with one or more P—C bonds
- C07F9/38—Phosphonic acids [RP(=O)(OH)2]; Thiophosphonic acids ; [RP(=X1)(X2H)2(X1, X2 are each independently O, S or Se)]
- C07F9/3804—Phosphonic acids [RP(=O)(OH)2]; Thiophosphonic acids ; [RP(=X1)(X2H)2(X1, X2 are each independently O, S or Se)] not used, see subgroups
- C07F9/3826—Acyclic unsaturated acids
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/28—Phosphorus compounds with one or more P—C bonds
- C07F9/38—Phosphonic acids [RP(=O)(OH)2]; Thiophosphonic acids ; [RP(=X1)(X2H)2(X1, X2 are each independently O, S or Se)]
- C07F9/40—Esters thereof
- C07F9/4003—Esters thereof the acid moiety containing a substituent or a structure which is considered as characteristic
- C07F9/4006—Esters of acyclic acids which can have further substituents on alkyl
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/645—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having two nitrogen atoms as the only ring hetero atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/645—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having two nitrogen atoms as the only ring hetero atoms
- C07F9/6509—Six-membered rings
- C07F9/650952—Six-membered rings having the nitrogen atoms in the positions 1 and 4
- C07F9/650994—Six-membered rings having the nitrogen atoms in the positions 1 and 4 condensed with carbocyclic rings or carbocyclic ring systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/04—Systems containing only non-condensed rings with a four-membered ring
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Biomedical Technology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Pain & Pain Management (AREA)
- Hospice & Palliative Care (AREA)
- Urology & Nephrology (AREA)
- Vascular Medicine (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Psychiatry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Plural Heterocyclic Compounds (AREA)
- Treatments For Attaching Organic Compounds To Fibrous Goods (AREA)
- Lubricants (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US64415791A | 1991-01-22 | 1991-01-22 | |
| US07/806,861 US5168103A (en) | 1991-01-22 | 1991-12-17 | [[2-(amino-3,4-dioxo-1-cyclobuten-1-yl) amino]alkyl]-acid derivatives |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| SK14492A3 SK14492A3 (en) | 1995-02-08 |
| SK280268B6 true SK280268B6 (sk) | 1999-10-08 |
Family
ID=27094416
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| SK144-92A SK280268B6 (sk) | 1991-01-22 | 1992-01-17 | N-substituované 3,4-diamino-1,2-dioxo-3-cyklobutén |
Country Status (23)
| Country | Link |
|---|---|
| US (2) | US5168103A (uk) |
| EP (1) | EP0496561B1 (uk) |
| JP (1) | JP3167770B2 (uk) |
| KR (1) | KR100206055B1 (uk) |
| AT (1) | ATE119873T1 (uk) |
| AU (1) | AU639629B2 (uk) |
| CA (1) | CA2059704C (uk) |
| CZ (1) | CZ286407B6 (uk) |
| DE (1) | DE69201655T2 (uk) |
| DK (1) | DK0496561T3 (uk) |
| ES (1) | ES2071428T3 (uk) |
| FI (1) | FI105551B (uk) |
| GR (1) | GR3015456T3 (uk) |
| HK (1) | HK1005588A1 (uk) |
| HU (2) | HU215838B (uk) |
| IE (1) | IE65873B1 (uk) |
| IL (1) | IL100679A (uk) |
| MX (1) | MX9200240A (uk) |
| NZ (1) | NZ241330A (uk) |
| RU (1) | RU2039035C1 (uk) |
| SK (1) | SK280268B6 (uk) |
| TW (1) | TW211564B (uk) |
| UA (1) | UA27741C2 (uk) |
Families Citing this family (49)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IL110309A0 (en) * | 1993-07-15 | 1994-10-21 | Univ Kentucky Res Found | A method of protecting against neuron loss |
| KR970002653B1 (ko) * | 1993-12-16 | 1997-03-07 | 엘지전자 주식회사 | 냉장고 |
| US5631401A (en) * | 1994-02-09 | 1997-05-20 | Abbott Laboratories | Inhibitors of protein farnesyltransferase and squalene synthase |
| US5466712A (en) * | 1994-11-04 | 1995-11-14 | American Home Products Corporation | Substituted n-aryl-1,2-diaminocyclobutene-3,4-diones |
| US5763474A (en) * | 1996-07-17 | 1998-06-09 | American Home Products Corporation | Substituted N-arylmethylamino derivatives of cyclobutene-3,4-diones |
| US5846999A (en) * | 1996-07-17 | 1998-12-08 | American Home Products Corporation | Substituted N-arylmethylamino derivatives of cyclobutene-3,4-diones |
| US5780505A (en) * | 1996-07-17 | 1998-07-14 | American Home Products Corporation | Substituted N-arylmethylamino derivatives of cyclobutene-3, 4-diones |
| US5750574A (en) * | 1996-07-17 | 1998-05-12 | American Home Products Corporation | Fluorinated N-arylmethylamino derivatives of cyclobutene-3,4-diones |
| JP2000513729A (ja) * | 1996-07-17 | 2000-10-17 | アメリカン・ホーム・プロダクツ・コーポレイション | シクロブテン―３，４―ジオンの置換ｎ―アリールメチルアミノ誘導体 |
| US5840764A (en) * | 1997-01-30 | 1998-11-24 | American Home Products Corporation | Substituted hydroxy-anilino derivatives of cyclobutene-3,4-diones |
| RU2205834C2 (ru) * | 1997-08-01 | 2003-06-10 | Американ Хоум Продактс Корпорейшн | Способ получения [2-((8,9)-диоксо-2,6-диазобицикло-[5.2.0]нон-1(7)-ен-2-ил)этил]фосфоновой кислоты, способ получения ди-с1-с6-алкилового эфира n-[3-(трет-бутилоксикарбониламино)пропил]-2-аминоэтилфосфорной кислоты, соединения |
| US5990307A (en) * | 1997-08-01 | 1999-11-23 | American Home Products Corporation | Process for the preparation of [2-((8.9)-Dioxo-2,6-Diazabicyclo [5.2.0]-Non-1(7)-en-2yl) Ethyl]Phosphonic acid |
| JPH1177971A (ja) * | 1997-09-05 | 1999-03-23 | Shinano Kenshi Co Ltd | ブランケット胴及び該ブランケット胴を備えたオフセット印刷装置 |
| PT1073432E (pt) | 1998-04-14 | 2007-10-22 | Gen Hospital Corp | Utilização da d-alanina ou da d-serina para o tratamento da esquizofrenia |
| US6376555B1 (en) | 1998-12-04 | 2002-04-23 | American Home Products Corporation | 4-substituted-3-substituted-amino-cyclobut-3-ene-1,2-diones and analogs thereof as novel potassium channel openers |
| US6166050A (en) * | 1998-12-14 | 2000-12-26 | American Home Products Corporation | 3,4-diamino-3-cyclobutene-1,2-dione derivatives which inhibit leukocyte adhesion mediated by VLA-4 |
| US7205404B1 (en) | 1999-03-05 | 2007-04-17 | Metabasis Therapeutics, Inc. | Phosphorus-containing prodrugs |
| KR100565008B1 (ko) * | 2000-02-01 | 2006-03-30 | 주식회사유한양행 | 4-하이드라지노-3-사이클로부텐-1,2-다이온 유도체 및이들의 제조 방법 |
| KR100742086B1 (ko) * | 2001-07-27 | 2007-07-23 | 주식회사유한양행 | 4-페닐-3-사이클로부텐-1,2-다이온 유도체 및 그의 제조방법 |
| UA78529C2 (en) * | 2001-10-10 | 2007-04-10 | Wyeth Corp | Derivatives of [[2-(amino-3,4-dioxo-1-cyclobutene-1-yl)amino]alkyl] acid for treating pain |
| CA2521394A1 (en) * | 2003-04-09 | 2004-10-28 | Wyeth | Pharmaceutical compositions for intranasal administration of [2-(8,9-dioxo-2,6-diazabicyclo[5.2.o]non-1 (7)-en-2-yl)alkyl] phosphonic acid and derivatives and methods of use thereof |
| CN1863810B (zh) * | 2003-04-09 | 2010-12-01 | 惠氏公司 | [2-(8，9-二氧代-2，6-二氮杂二环[5.2.0]壬-1(7)-烯-2-基)烷基]膦酸衍生物及其作为n-甲基-d-天冬氨酸(nmda)受体拮抗剂的应用 |
| US20050142192A1 (en) * | 2003-10-15 | 2005-06-30 | Wyeth | Oral administration of [2-(8,9-dioxo-2,6-diazabicyclo[5.2.0]non-1(7)-en-2-yl)alkyl] phosphonic acid and derivatives |
| GT200400213A (es) * | 2003-10-22 | 2007-09-05 | Metodos para la preparacion del acido {2-[(8,9)-dioxo-2,6-diaza-biciclo[5.2.0]-non-1(7)-en-2-il]etil} fosfonico y esteres del mismo | |
| WO2005085197A1 (en) * | 2004-02-27 | 2005-09-15 | Schering Corporation | Cyclobutenedione groups-containing compounds as inhibitors of hepatitis c virus ns3 serine protease |
| US7635694B2 (en) | 2004-02-27 | 2009-12-22 | Schering Corporation | Cyclobutenedione-containing compounds as inhibitors of hepatitis C virus NS3 serine protease |
| EP1797104B1 (en) * | 2004-10-08 | 2009-11-25 | Wyeth | Derivatives of [2-(8,9-dioxo-2,6-diazabicyclo[5.2.0]non-1(7)-en-2-yl)alkyl]phosphonic acid and method of making them |
| EP2195031A1 (en) * | 2007-08-27 | 2010-06-16 | Wyeth a Corporation of the State of Delaware | Compositions and methods employing nmda antagonists for achieving an anesthetic-sparing effect |
| ES2553968T3 (es) | 2008-09-18 | 2015-12-15 | Northwestern University | Moduladores del receptor NMDA y sus usos |
| KR20110139274A (ko) * | 2009-03-19 | 2011-12-28 | 와이어쓰 엘엘씨 | ［2-(8,9-다이옥소-2,6-다이아자바이사이클로［5.2.0］논-1(7)-엔-2-일)에틸］포스폰산 및 이의 전구체의 제조 방법 |
| US9737531B2 (en) | 2012-07-12 | 2017-08-22 | Glytech, Llc | Composition and method for treatment of depression and psychosis in humans |
| CN105229010A (zh) | 2013-01-29 | 2016-01-06 | 阿普廷伊克斯股份有限公司 | 螺-内酰胺nmda受体调节剂及其用途 |
| MX2015009772A (es) | 2013-01-29 | 2016-05-31 | Aptinyx Inc | Moduladores de receptores nmda de espiro-lactama y sus usos. |
| CN105026401A (zh) | 2013-01-29 | 2015-11-04 | 诺雷克斯股份有限公司 | 螺-内酰胺nmda受体调节剂及其用途 |
| KR102280616B1 (ko) | 2013-01-29 | 2021-07-21 | 앱티닉스 인크. | 스피로-락탐 nmda 수용체 조절인자 및 그의 용도 |
| US9708335B2 (en) | 2013-01-29 | 2017-07-18 | Apytinyx Inc. | Spiro-lactam NMDA receptor modulators and uses thereof |
| EP3105238A4 (en) | 2014-02-13 | 2017-11-08 | Ligand Pharmaceuticals, Inc. | Prodrug compounds and their uses |
| EP3164136A4 (en) | 2014-07-02 | 2018-04-04 | Ligand Pharmaceuticals, Inc. | Prodrug compounds and uses therof |
| WO2017201285A1 (en) | 2016-05-19 | 2017-11-23 | Aptinyx Inc. | Spiro-lactam nmda receptor modulators and uses thereof |
| CA3024606C (en) | 2016-05-19 | 2019-09-03 | Aptinyx Inc. | Spiro-lactam nmda receptor modulators and uses thereof |
| SG10202101055VA (en) | 2016-08-01 | 2021-03-30 | Aptinyx Inc | Spiro-lactam nmda receptor modulators and uses thereof |
| SG11201900558RA (en) | 2016-08-01 | 2019-02-27 | Aptinyx Inc | Spiro-lactam nmda receptor modulators and uses thereof |
| AU2017305240B2 (en) | 2016-08-01 | 2021-12-09 | Aptinyx Inc. | Spiro-lactam NMDA receptor modulators and uses thereof |
| CN109661398B (zh) | 2016-08-01 | 2022-07-05 | 阿普廷伊克斯股份有限公司 | 螺-内酰胺和二-螺-内酰胺nmda受体调节剂及其用途 |
| WO2018026798A1 (en) | 2016-08-01 | 2018-02-08 | Aptinyx Inc. | Spiro-lactam nmda modulators and methods of using same |
| AU2018284335A1 (en) | 2017-06-12 | 2020-01-30 | Glytech Llc. | Treatment of depression with NMDA antagonists and D2/5HT2A or selective 5HT2A antagonists |
| CN111788196A (zh) | 2018-01-09 | 2020-10-16 | 配体药物公司 | 缩醛化合物及其治疗用途 |
| MX2020008107A (es) | 2018-01-31 | 2020-09-25 | Aptinyx Inc | Moduladores del receptor nmda espiro-lactama y usos de los mismos. |
| US12012413B2 (en) | 2019-11-11 | 2024-06-18 | Tenacia Biotechnology (Hong Kong) Co., Limited | Methods of treating painful diabetic peripheral neuropathy |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE1518660A1 (de) * | 1965-07-09 | 1969-08-14 | Huels Chemische Werke Ag | Verfahren zur Herstellung aminosubstituierter Dioxocyclobutene |
| GB1563090A (en) * | 1975-07-31 | 1980-03-19 | Smith Kline French Lab | Cyclobutene-diones |
| US4390701A (en) * | 1981-05-18 | 1983-06-28 | Bristol-Myers Company | 1-Amino-2-[3-(3-piperidinomethylphenoxy)propylamino]cyclobutene-3,4-dione |
| US4521625A (en) * | 1982-10-02 | 1985-06-04 | Smith Kline & French Laboratories Limited | Dioxocyclobutene compounds |
| US4927970A (en) * | 1987-05-14 | 1990-05-22 | Bristol-Myers Company | Substituted 3-cyclobutene-1,2-dione intermediates |
| US4902687A (en) * | 1989-03-27 | 1990-02-20 | Eli Lilly And Company | Excitatory amino acid receptor antagonists |
-
1991
- 1991-12-17 US US07/806,861 patent/US5168103A/en not_active Expired - Lifetime
-
1992
- 1992-01-16 IL IL10067992A patent/IL100679A/en not_active IP Right Cessation
- 1992-01-17 NZ NZ241330A patent/NZ241330A/en not_active IP Right Cessation
- 1992-01-17 AU AU10301/92A patent/AU639629B2/en not_active Ceased
- 1992-01-17 SK SK144-92A patent/SK280268B6/sk not_active IP Right Cessation
- 1992-01-17 CZ CS1992144A patent/CZ286407B6/cs not_active IP Right Cessation
- 1992-01-20 AT AT92300472T patent/ATE119873T1/de not_active IP Right Cessation
- 1992-01-20 TW TW081100363A patent/TW211564B/zh not_active IP Right Cessation
- 1992-01-20 EP EP92300472A patent/EP0496561B1/en not_active Expired - Lifetime
- 1992-01-20 RU SU925010645A patent/RU2039035C1/ru active
- 1992-01-20 JP JP00738592A patent/JP3167770B2/ja not_active Expired - Fee Related
- 1992-01-20 ES ES92300472T patent/ES2071428T3/es not_active Expired - Lifetime
- 1992-01-20 CA CA002059704A patent/CA2059704C/en not_active Expired - Fee Related
- 1992-01-20 DK DK92300472.5T patent/DK0496561T3/da active
- 1992-01-20 DE DE69201655T patent/DE69201655T2/de not_active Expired - Fee Related
- 1992-01-20 MX MX9200240A patent/MX9200240A/es not_active IP Right Cessation
- 1992-01-21 FI FI920261A patent/FI105551B/fi active
- 1992-01-21 HU HU9200192A patent/HU215838B/hu not_active IP Right Cessation
- 1992-01-21 IE IE920176A patent/IE65873B1/en not_active IP Right Cessation
- 1992-01-21 KR KR1019920000780A patent/KR100206055B1/ko not_active IP Right Cessation
- 1992-04-29 US US07/875,925 patent/US5240946A/en not_active Expired - Lifetime
-
1993
- 1993-06-15 UA UA93002900A patent/UA27741C2/uk unknown
-
1995
- 1995-03-17 GR GR950400588T patent/GR3015456T3/el unknown
- 1995-06-29 HU HU95P/P00530P patent/HU211653A9/hu unknown
-
1998
- 1998-05-29 HK HK98104652A patent/HK1005588A1/xx not_active IP Right Cessation
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| SK280268B6 (sk) | N-substituované 3,4-diamino-1,2-dioxo-3-cyklobutén | |
| JP3534765B2 (ja) | 喘息治療用のニューロキニン２受容体拮抗薬としての新規な４−ピペリジニル置換ラクタム | |
| HUT53879A (en) | Improved process for producing decahydro-isoquinoline derivatives | |
| EP0934326A1 (de) | Substituierte aminoalkanphosphonsäuren | |
| WO2008097819A2 (en) | Chemical compounds | |
| JPH04234857A (ja) | ３，５−ジ置換２−イソキサゾリンおよびイソキサゾール、それらの製法およびそれらを含有する薬学的組成物 | |
| CZ308392A3 (en) | Benzimidazolephosphonoamino acids, process of their preparation and pharmaceutical preparations containing such acids | |
| CA2323047C (en) | Prodrugs of benzofuranylmethyl carbamate nk, antagonists | |
| SU1709912A3 (ru) | Способ получени пролинсодержащего эфира 4-фенилбутилфосфоновой кислоты | |
| WO1995017410A1 (en) | Heterocyclic compounds | |
| CZ80993A3 (en) | Novel heterocyclic compounds as antagonists of amino acid receptors excitation, processes of their preparation and their use | |
| EP0879238B1 (en) | Benzimidazole phosphono-amino acids | |
| RU2368616C2 (ru) | Производные фосфиновой кислоты | |
| US6596709B1 (en) | 6-sulphanoyl-3-quinolylphosphonic acid compounds | |
| JPH05222072A (ja) | α−アミノ酸 | |
| JP2000500157A (ja) | 複素環式化学化合物 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MM4A | Patent lapsed due to non-payment of maintenance fees |
Effective date: 20100117 |