FI105551B - Menetelmä terapeuttisesti käyttökelpoisten [[(2-amino-3,4-diokso-1-syklobuten-1-yyli)amino]alkyyli]happojohdannaisten valmistamiseksi ja menetelmässä käytettäviä välituotteita - Google Patents
Menetelmä terapeuttisesti käyttökelpoisten [[(2-amino-3,4-diokso-1-syklobuten-1-yyli)amino]alkyyli]happojohdannaisten valmistamiseksi ja menetelmässä käytettäviä välituotteita Download PDFInfo
- Publication number
- FI105551B FI105551B FI920261A FI920261A FI105551B FI 105551 B FI105551 B FI 105551B FI 920261 A FI920261 A FI 920261A FI 920261 A FI920261 A FI 920261A FI 105551 B FI105551 B FI 105551B
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- FI
- Finland
- Prior art keywords
- dioxo
- amino
- cyclobuten
- carbon atoms
- formula
- Prior art date
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- -1 2-amino-3,4-dioxo-1-cyclobutene-1-yl Chemical group 0.000 title claims abstract description 98
- 125000000217 alkyl group Chemical group 0.000 title claims abstract description 46
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 title claims abstract description 37
- 239000002253 acid Substances 0.000 title claims abstract description 21
- 238000000034 method Methods 0.000 title claims description 44
- 230000008569 process Effects 0.000 title claims description 21
- 238000002360 preparation method Methods 0.000 title claims description 8
- 239000000543 intermediate Substances 0.000 title abstract description 13
- 150000003839 salts Chemical class 0.000 claims abstract description 33
- 125000002947 alkylene group Chemical group 0.000 claims abstract description 11
- 125000004450 alkenylene group Chemical group 0.000 claims abstract description 9
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 9
- 125000003342 alkenyl group Chemical group 0.000 claims abstract description 7
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims abstract description 7
- 150000001875 compounds Chemical class 0.000 claims description 92
- 125000004432 carbon atom Chemical group C* 0.000 claims description 53
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 32
- 229910052739 hydrogen Inorganic materials 0.000 claims description 28
- 239000001257 hydrogen Substances 0.000 claims description 28
- 125000006239 protecting group Chemical group 0.000 claims description 20
- 150000002431 hydrogen Chemical class 0.000 claims description 18
- MJUJXFBTEFXVKU-UHFFFAOYSA-N diethyl phosphonate Chemical compound CCOP(=O)OCC MJUJXFBTEFXVKU-UHFFFAOYSA-N 0.000 claims description 16
- ABLZXFCXXLZCGV-UHFFFAOYSA-N Phosphorous acid Chemical compound OP(O)=O ABLZXFCXXLZCGV-UHFFFAOYSA-N 0.000 claims description 15
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 12
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 12
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 claims description 10
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 9
- LFKDJXLFVYVEFG-UHFFFAOYSA-N tert-butyl carbamate Chemical compound CC(C)(C)OC(N)=O LFKDJXLFVYVEFG-UHFFFAOYSA-N 0.000 claims description 9
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 7
- 125000003884 phenylalkyl group Chemical group 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
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 claims description 5
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 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
- 102100035593 POU domain, class 2, transcription factor 1 Human genes 0.000 claims description 3
- 101710084414 POU domain, class 2, transcription factor 1 Proteins 0.000 claims description 3
- 229910052783 alkali metal Inorganic materials 0.000 claims description 3
- 125000005394 methallyl group Chemical group 0.000 claims description 3
- 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 claims description 2
- 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 claims description 2
- MJVNCSHHLBOQGB-UHFFFAOYSA-N 2-[2-[(2-amino-3,4-dioxocyclobuten-1-yl)amino]ethyl]-1,2,4-oxadiazolidine-3,5-dione Chemical compound O=C1C(=O)C(N)=C1NCCN1C(=O)NC(=O)O1 MJVNCSHHLBOQGB-UHFFFAOYSA-N 0.000 claims description 2
- DPXKALHPOMCHBL-UHFFFAOYSA-N 3-(2-diethoxyphosphorylethylamino)-4-ethoxycyclobut-3-ene-1,2-dione Chemical group CCOC1=C(NCCP(=O)(OCC)OCC)C(=O)C1=O DPXKALHPOMCHBL-UHFFFAOYSA-N 0.000 claims description 2
- OANHISBGZJOZQD-UHFFFAOYSA-N 3-(8,9-dioxo-2,6-diazabicyclo[5.2.0]non-1(7)-en-6-yl)propanoic acid Chemical compound OC(=O)CCN1CCCNC2=C1C(=O)C2=O OANHISBGZJOZQD-UHFFFAOYSA-N 0.000 claims description 2
- 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 description 2
- 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 description 2
- ZPXHSVJAPFNZRP-UHFFFAOYSA-N 3-[[2-(methylamino)-3,4-dioxocyclobuten-1-yl]amino]propanoic acid Chemical compound CNC1=C(NCCC(O)=O)C(=O)C1=O ZPXHSVJAPFNZRP-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
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 claims description 2
- 150000001340 alkali metals Chemical class 0.000 claims description 2
- 229910052784 alkaline earth metal Inorganic materials 0.000 claims description 2
- 150000001342 alkaline earth metals Chemical class 0.000 claims description 2
- 125000003277 amino group Chemical group 0.000 claims description 2
- 150000003863 ammonium salts Chemical class 0.000 claims description 2
- 150000001540 azides Chemical class 0.000 claims description 2
- CVXBEEMKQHEXEN-UHFFFAOYSA-N carbaryl Chemical compound C1=CC=C2C(OC(=O)NC)=CC=CC2=C1 CVXBEEMKQHEXEN-UHFFFAOYSA-N 0.000 claims description 2
- 229910052744 lithium Inorganic materials 0.000 claims description 2
- 125000005499 phosphonyl group Chemical group 0.000 claims description 2
- 238000009877 rendering Methods 0.000 claims description 2
- DLALIZXWAXIZHS-UHFFFAOYSA-N tert-butyl 2-[(2-ethoxy-3,4-dioxocyclobuten-1-yl)-[3-(phenylmethoxycarbonylamino)propyl]amino]acetate Chemical compound O=C1C(=O)C(OCC)=C1N(CC(=O)OC(C)(C)C)CCCNC(=O)OCC1=CC=CC=C1 DLALIZXWAXIZHS-UHFFFAOYSA-N 0.000 claims description 2
- 125000003831 tetrazolyl group Chemical group 0.000 claims description 2
- 125000004369 butenyl group Chemical group C(=CCC)* 0.000 claims 2
- 125000006022 2-methyl-2-propenyl group Chemical group 0.000 claims 1
- NHMBCTRHEQQAKO-UHFFFAOYSA-N 3-(3-diethoxyphosphorylpropylamino)-4-ethoxycyclobut-3-ene-1,2-dione Chemical compound CCOC1=C(NCCCP(=O)(OCC)OCC)C(=O)C1=O NHMBCTRHEQQAKO-UHFFFAOYSA-N 0.000 claims 1
- BYXFEMQKSMEECE-UHFFFAOYSA-N 3-(4-diethoxyphosphorylbutylamino)-4-ethoxycyclobut-3-ene-1,2-dione Chemical compound CCOC1=C(NCCCCP(=O)(OCC)OCC)C(=O)C1=O BYXFEMQKSMEECE-UHFFFAOYSA-N 0.000 claims 1
- 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 1
- PWVHCTNLZPIECG-UHFFFAOYSA-N 4-[2-diethoxyphosphorylethyl-(2-ethoxy-3,4-dioxocyclobuten-1-yl)amino]butylcarbamic acid Chemical compound CCOC1=C(N(CCCCNC(O)=O)CCP(=O)(OCC)OCC)C(=O)C1=O PWVHCTNLZPIECG-UHFFFAOYSA-N 0.000 claims 1
- 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 claims 1
- 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 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 claims 1
- QJGONWXMHNMVQF-UHFFFAOYSA-N [(2-amino-3,4-dioxocyclobuten-1-yl)methylamino]methylphosphonic acid Chemical compound NC1=C(CNCP(O)(O)=O)C(=O)C1=O QJGONWXMHNMVQF-UHFFFAOYSA-N 0.000 claims 1
- 101150047356 dec-1 gene Proteins 0.000 claims 1
- NXTPAKSNVIEBTE-UHFFFAOYSA-N ethyl 2-[(2-amino-3,4-dioxocyclobuten-1-yl)amino]acetate Chemical compound CCOC(=O)CNC1=C(N)C(=O)C1=O NXTPAKSNVIEBTE-UHFFFAOYSA-N 0.000 claims 1
- 150000004702 methyl esters Chemical class 0.000 claims 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 100
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 82
- 239000000243 solution Substances 0.000 description 55
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 54
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 43
- 229910001868 water Inorganic materials 0.000 description 43
- 239000007787 solid Substances 0.000 description 42
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 39
- 238000000921 elemental analysis Methods 0.000 description 38
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 36
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 33
- 238000005160 1H NMR spectroscopy Methods 0.000 description 27
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 27
- 239000011541 reaction mixture Substances 0.000 description 25
- 239000012299 nitrogen atmosphere Substances 0.000 description 23
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 19
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 19
- 239000003921 oil Substances 0.000 description 18
- 235000019198 oils Nutrition 0.000 description 18
- 238000004587 chromatography analysis Methods 0.000 description 17
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 16
- 238000006243 chemical reaction Methods 0.000 description 15
- 239000000203 mixture Substances 0.000 description 15
- 238000010828 elution Methods 0.000 description 14
- 238000010992 reflux Methods 0.000 description 14
- 239000000741 silica gel Substances 0.000 description 14
- 229910002027 silica gel Inorganic materials 0.000 description 14
- 238000005481 NMR spectroscopy Methods 0.000 description 13
- 239000002904 solvent Substances 0.000 description 13
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 12
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 12
- HOKKHZGPKSLGJE-GSVOUGTGSA-N N-Methyl-D-aspartic acid Chemical compound CN[C@@H](C(O)=O)CC(O)=O HOKKHZGPKSLGJE-GSVOUGTGSA-N 0.000 description 12
- 239000000376 reactant Substances 0.000 description 12
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 11
- HOKKHZGPKSLGJE-UHFFFAOYSA-N N-methyl-D-aspartic acid Natural products CNC(C(O)=O)CC(O)=O HOKKHZGPKSLGJE-UHFFFAOYSA-N 0.000 description 11
- 239000007788 liquid Substances 0.000 description 11
- 238000003756 stirring Methods 0.000 description 11
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 10
- 150000002148 esters Chemical class 0.000 description 10
- 239000000725 suspension Substances 0.000 description 10
- UCMIRNVEIXFBKS-UHFFFAOYSA-N beta-alanine Chemical compound NCCC(O)=O UCMIRNVEIXFBKS-UHFFFAOYSA-N 0.000 description 9
- IYYIVELXUANFED-UHFFFAOYSA-N bromo(trimethyl)silane Chemical compound C[Si](C)(C)Br IYYIVELXUANFED-UHFFFAOYSA-N 0.000 description 9
- 238000010438 heat treatment Methods 0.000 description 9
- 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 8
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 8
- 235000019253 formic acid Nutrition 0.000 description 8
- 239000011734 sodium Substances 0.000 description 8
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 7
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 6
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 6
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- 239000010410 layer Substances 0.000 description 6
- 239000000047 product Substances 0.000 description 6
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 5
- 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 5
- 241000699670 Mus sp. Species 0.000 description 5
- 239000004480 active ingredient Substances 0.000 description 5
- 239000005557 antagonist Substances 0.000 description 5
- PUJDIJCNWFYVJX-UHFFFAOYSA-N benzyl carbamate Chemical compound NC(=O)OCC1=CC=CC=C1 PUJDIJCNWFYVJX-UHFFFAOYSA-N 0.000 description 5
- 238000004992 fast atom bombardment mass spectroscopy Methods 0.000 description 5
- 238000003818 flash chromatography Methods 0.000 description 5
- 238000005984 hydrogenation reaction Methods 0.000 description 5
- 239000012442 inert solvent Substances 0.000 description 5
- 229910052757 nitrogen Inorganic materials 0.000 description 5
- 229910000104 sodium hydride Inorganic materials 0.000 description 5
- 159000000000 sodium salts Chemical class 0.000 description 5
- 239000004471 Glycine Substances 0.000 description 4
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 4
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
- 150000001412 amines Chemical class 0.000 description 4
- 229910021529 ammonia Inorganic materials 0.000 description 4
- 229940000635 beta-alanine Drugs 0.000 description 4
- 210000004556 brain Anatomy 0.000 description 4
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 4
- 239000000969 carrier Substances 0.000 description 4
- 150000004985 diamines Chemical class 0.000 description 4
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- 238000007363 ring formation reaction Methods 0.000 description 4
- 229920006395 saturated elastomer Polymers 0.000 description 4
- 229910052708 sodium Inorganic materials 0.000 description 4
- 239000012312 sodium hydride Substances 0.000 description 4
- XFNJVJPLKCPIBV-UHFFFAOYSA-N trimethylenediamine Chemical compound NCCCN XFNJVJPLKCPIBV-UHFFFAOYSA-N 0.000 description 4
- 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
- 206010008111 Cerebral haemorrhage Diseases 0.000 description 3
- 206010052904 Musculoskeletal stiffness Diseases 0.000 description 3
- 102000004868 N-Methyl-D-Aspartate Receptors Human genes 0.000 description 3
- 108090001041 N-Methyl-D-Aspartate Receptors Proteins 0.000 description 3
- 241000700159 Rattus Species 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
- 230000009471 action Effects 0.000 description 3
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- 239000002585 base Substances 0.000 description 3
- WURBFLDFSFBTLW-UHFFFAOYSA-N benzil Chemical compound C=1C=CC=CC=1C(=O)C(=O)C1=CC=CC=C1 WURBFLDFSFBTLW-UHFFFAOYSA-N 0.000 description 3
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 3
- KXDHJXZQYSOELW-UHFFFAOYSA-N carbonic acid monoamide Natural products NC(O)=O KXDHJXZQYSOELW-UHFFFAOYSA-N 0.000 description 3
- 239000012230 colorless oil Substances 0.000 description 3
- 239000013058 crude material Substances 0.000 description 3
- 239000002552 dosage form Substances 0.000 description 3
- 230000002461 excitatory amino acid Effects 0.000 description 3
- 239000003257 excitatory amino acid Substances 0.000 description 3
- ZHNUHDYFZUAESO-UHFFFAOYSA-N formamide Substances NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 3
- 125000001475 halogen functional group Chemical group 0.000 description 3
- 239000003703 n methyl dextro aspartic acid receptor blocking agent Substances 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 208000015122 neurodegenerative disease Diseases 0.000 description 3
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 3
- 239000012044 organic layer Substances 0.000 description 3
- 238000007911 parenteral administration Methods 0.000 description 3
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- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 3
- 229910000029 sodium carbonate Inorganic materials 0.000 description 3
- 229910052938 sodium sulfate Inorganic materials 0.000 description 3
- 235000011152 sodium sulphate Nutrition 0.000 description 3
- 238000006467 substitution reaction Methods 0.000 description 3
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 3
- 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 3
- 238000005406 washing Methods 0.000 description 3
- BDYHNCZIGYIOGJ-DUXPYHPUSA-N (e)-2-amino-4-methyl-5-phosphonopent-3-enoic acid Chemical compound OP(=O)(O)CC(/C)=C/C(N)C(O)=O BDYHNCZIGYIOGJ-DUXPYHPUSA-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
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- 239000002244 precipitate Substances 0.000 description 1
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- WGYKZJWCGVVSQN-UHFFFAOYSA-N propylamine Chemical group CCCN WGYKZJWCGVVSQN-UHFFFAOYSA-N 0.000 description 1
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- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 1
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- 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
- 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
- SKVQUYXQAOAZHV-UHFFFAOYSA-N tert-butyl n-[3-[2-diethoxyphosphorylethyl-(2-ethoxy-3,4-dioxocyclobuten-1-yl)amino]-2-hydroxypropyl]carbamate Chemical compound CCOC1=C(N(CCP(=O)(OCC)OCC)CC(O)CNC(=O)OC(C)(C)C)C(=O)C1=O SKVQUYXQAOAZHV-UHFFFAOYSA-N 0.000 description 1
- 150000003536 tetrazoles Chemical class 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
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- 238000005303 weighing Methods 0.000 description 1
Classifications
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- 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
-
- 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
-
- 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
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P25/08—Antiepileptics; Anticonvulsants
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- 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
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- 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
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- 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
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- C—CHEMISTRY; METALLURGY
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- 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
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- C—CHEMISTRY; METALLURGY
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- 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
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- 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
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- 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
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- 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
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- 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
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- 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)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Lubricants (AREA)
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US64415791A | 1991-01-22 | 1991-01-22 | |
| US64415791 | 1991-01-22 | ||
| US80686191 | 1991-12-17 | ||
| 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 (3)
| Publication Number | Publication Date |
|---|---|
| FI920261A0 FI920261A0 (fi) | 1992-01-21 |
| FI920261L FI920261L (fi) | 1992-08-23 |
| FI105551B true FI105551B (fi) | 2000-09-15 |
Family
ID=27094416
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| FI920261A FI105551B (fi) | 1991-01-22 | 1992-01-21 | Menetelmä terapeuttisesti käyttökelpoisten [[(2-amino-3,4-diokso-1-syklobuten-1-yyli)amino]alkyyli]happojohdannaisten valmistamiseksi ja menetelmässä käytettäviä välituotteita |
Country Status (23)
| Country | Link |
|---|---|
| US (2) | US5168103A (OSRAM) |
| EP (1) | EP0496561B1 (OSRAM) |
| JP (1) | JP3167770B2 (OSRAM) |
| KR (1) | KR100206055B1 (OSRAM) |
| AT (1) | ATE119873T1 (OSRAM) |
| AU (1) | AU639629B2 (OSRAM) |
| CA (1) | CA2059704C (OSRAM) |
| CZ (1) | CZ286407B6 (OSRAM) |
| DE (1) | DE69201655T2 (OSRAM) |
| DK (1) | DK0496561T3 (OSRAM) |
| ES (1) | ES2071428T3 (OSRAM) |
| FI (1) | FI105551B (OSRAM) |
| GR (1) | GR3015456T3 (OSRAM) |
| HK (1) | HK1005588A1 (OSRAM) |
| HU (2) | HU215838B (OSRAM) |
| IE (1) | IE65873B1 (OSRAM) |
| IL (1) | IL100679A (OSRAM) |
| MX (1) | MX9200240A (OSRAM) |
| NZ (1) | NZ241330A (OSRAM) |
| RU (1) | RU2039035C1 (OSRAM) |
| SK (1) | SK280268B6 (OSRAM) |
| TW (1) | TW211564B (OSRAM) |
| UA (1) | UA27741C2 (OSRAM) |
Families Citing this family (50)
| 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 |
| UA67725C2 (en) * | 1996-06-03 | 2004-07-15 | Cephalon Inc | K-252a derivatives and a method for improvement of functioning and cell survival enhancement |
| 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 |
| 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 |
| US5750574A (en) * | 1996-07-17 | 1998-05-12 | American Home Products Corporation | Fluorinated 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 |
| US5840764A (en) * | 1997-01-30 | 1998-11-24 | American Home Products Corporation | Substituted hydroxy-anilino derivatives of cyclobutene-3,4-diones |
| 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 |
| AU746119B2 (en) * | 1997-08-01 | 2002-04-18 | Wyeth | Process for the preparation of (2-((8,9)- dioxo-2,6-diazabicyclo (5.2.0)-non-1(7)-en-2-yl)-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 |
| EP1844769A3 (en) | 1998-04-14 | 2010-02-10 | The General Hospital Corporation | Methods for treating neuropsychiatric disorders |
| 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 |
| EP1611144B1 (en) * | 2003-04-09 | 2010-09-15 | Wyeth LLC | Derivatives of 2-(8,9-dioxo-2,6-diazabicyclo(5.2.0)non-1(7)-en-2-yl)alkyl phosphonic acid and their use as n-methyl-d-aspartate (nmda) recetor antagonists |
| WO2004091633A1 (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 |
| 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 | |
| US7635694B2 (en) | 2004-02-27 | 2009-12-22 | Schering Corporation | Cyclobutenedione-containing compounds as inhibitors of hepatitis C virus NS3 serine protease |
| CA2557301A1 (en) * | 2004-02-27 | 2005-09-15 | Schering Corporation | Cyclobutenedione groups-containing compounds as inhibitors of hepatitis c virus ns3 serine protease |
| CN101072784B (zh) * | 2004-10-08 | 2011-05-04 | 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]膦酸衍生物及其制备方法 |
| US20090061024A1 (en) * | 2007-08-27 | 2009-03-05 | Wyeth | Compositions and methods employing nmda antagonists for achieving an anesthetic-sparing effect |
| CA2740628C (en) | 2008-09-18 | 2018-05-01 | Naurex, Inc. | Nmda receptor modulators and uses thereof |
| MX2011009716A (es) | 2009-03-19 | 2011-10-17 | Wyeth Llc | Metodos para la preparacion de acido [2-(8,9-dioxo)-2,6-diazabicic lo[5.2.0]non-1(7)-en-2-il)etil]fosfonico y precursores de este. |
| US9737531B2 (en) | 2012-07-12 | 2017-08-22 | Glytech, Llc | Composition and method for treatment of depression and psychosis in humans |
| DK2951183T3 (da) | 2013-01-29 | 2019-06-03 | Aptinyx Inc | Spiro-lactam-nmda-receptormodulatorer og anvendelser heraf |
| EA031905B1 (ru) | 2013-01-29 | 2019-03-29 | Аптиникс Инк. | Спиролактамные модуляторы рецептора nmda и их применение |
| PE20151438A1 (es) | 2013-01-29 | 2015-10-10 | Naurex Inc | Moduladores de receptores nmda de espiro-lactama y sus usos |
| ES2618421T3 (es) | 2013-01-29 | 2017-06-21 | Aptinyx Inc. | Moduladores espiro-lactama del receptor NMDA y usos de los mismos |
| US9828384B2 (en) | 2013-01-29 | 2017-11-28 | Aptinyx Inc. | Spiro-lactam NMDA receptor modulators and uses thereof |
| WO2015123352A1 (en) | 2014-02-13 | 2015-08-20 | Ligand Pharmaceuticals, Inc. | Prodrug compounds and their uses |
| CN106687118A (zh) | 2014-07-02 | 2017-05-17 | 配体药物公司 | 前药化合物及其用途 |
| MX378566B (es) | 2016-05-19 | 2025-03-11 | Aptinyx Inc | Moduladores del receptor espiro-lactama n-metil-d-aspartato y usos de los mismos. |
| WO2017201285A1 (en) | 2016-05-19 | 2017-11-23 | 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 |
| KR102538803B1 (ko) | 2016-08-01 | 2023-06-01 | 앱티닉스 인크. | 스피로-락탐 nmda 조정제 및 그의 사용 방법 |
| EP3490974B1 (en) | 2016-08-01 | 2023-12-06 | Tenacia Biotechnology (Hong Kong) Co., Limited | Spiro-lactam nmda receptor modulators and uses thereof |
| SG11201900546UA (en) | 2016-08-01 | 2019-02-27 | Aptinyx Inc | Spiro-lactam and bis-spiro-lactam nmda receptor modulators and uses thereof |
| EA201990424A1 (ru) | 2016-08-01 | 2019-08-30 | Аптиникс Инк. | Спиролактамовые модуляторы nmda-рецептора и их применение |
| CA3067162A1 (en) | 2017-06-12 | 2018-12-20 | 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 |
| US11578072B2 (en) | 2018-01-31 | 2023-02-14 | Aptinyx Inc. | Spiro-lactam NMDA receptor modulators and uses thereof |
| 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 |
| US4466970A (en) * | 1982-10-02 | 1984-08-21 | 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 AU AU10301/92A patent/AU639629B2/en not_active Ceased
- 1992-01-17 NZ NZ241330A patent/NZ241330A/en not_active IP Right Cessation
- 1992-01-17 CZ CS1992144A patent/CZ286407B6/cs not_active IP Right Cessation
- 1992-01-17 SK SK144-92A patent/SK280268B6/sk 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 AT AT92300472T patent/ATE119873T1/de not_active IP Right Cessation
- 1992-01-20 ES ES92300472T patent/ES2071428T3/es not_active Expired - Lifetime
- 1992-01-20 DE DE69201655T patent/DE69201655T2/de not_active Expired - Fee Related
- 1992-01-20 DK DK92300472.5T patent/DK0496561T3/da active
- 1992-01-20 CA CA002059704A patent/CA2059704C/en not_active Expired - Fee Related
- 1992-01-20 RU SU925010645A patent/RU2039035C1/ru active
- 1992-01-20 MX MX9200240A patent/MX9200240A/es not_active IP Right Cessation
- 1992-01-20 JP JP00738592A patent/JP3167770B2/ja not_active Expired - Fee Related
- 1992-01-21 IE IE920176A patent/IE65873B1/en not_active IP Right Cessation
- 1992-01-21 HU HU9200192A patent/HU215838B/hu not_active IP Right Cessation
- 1992-01-21 FI FI920261A patent/FI105551B/fi active
- 1992-01-21 KR KR1019920000780A patent/KR100206055B1/ko not_active Expired - Fee Related
- 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/en not_active IP Right Cessation
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