JP2004538258A - 抗癲癇誘発剤 - Google Patents
抗癲癇誘発剤 Download PDFInfo
- Publication number
- JP2004538258A JP2004538258A JP2002572418A JP2002572418A JP2004538258A JP 2004538258 A JP2004538258 A JP 2004538258A JP 2002572418 A JP2002572418 A JP 2002572418A JP 2002572418 A JP2002572418 A JP 2002572418A JP 2004538258 A JP2004538258 A JP 2004538258A
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- JP
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- Prior art keywords
- compound
- subject
- epileptogenesis
- group
- alanine
- Prior art date
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- 239000001961 anticonvulsive agent Substances 0.000 title description 41
- 150000001875 compounds Chemical class 0.000 claims abstract description 353
- 238000000034 method Methods 0.000 claims abstract description 221
- 206010015037 epilepsy Diseases 0.000 claims abstract description 31
- 230000008579 epileptogenesis Effects 0.000 claims description 106
- -1 phenoxy-substituted phenyl Chemical group 0.000 claims description 103
- 125000000217 alkyl group Chemical group 0.000 claims description 99
- UCMIRNVEIXFBKS-UHFFFAOYSA-N beta-alanine Chemical class NCCC(O)=O UCMIRNVEIXFBKS-UHFFFAOYSA-N 0.000 claims description 97
- 229910052739 hydrogen Inorganic materials 0.000 claims description 94
- 239000001257 hydrogen Substances 0.000 claims description 94
- 125000003118 aryl group Chemical group 0.000 claims description 89
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 81
- 125000005161 aryl oxy carbonyl group Chemical group 0.000 claims description 73
- 150000002431 hydrogen Chemical class 0.000 claims description 68
- 125000004448 alkyl carbonyl group Chemical group 0.000 claims description 65
- 150000003839 salts Chemical class 0.000 claims description 65
- 229940000635 beta-alanine Drugs 0.000 claims description 63
- 125000005129 aryl carbonyl group Chemical group 0.000 claims description 62
- 125000003342 alkenyl group Chemical group 0.000 claims description 51
- 125000000304 alkynyl group Chemical group 0.000 claims description 51
- 150000002148 esters Chemical class 0.000 claims description 45
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- 108090001041 N-Methyl-D-Aspartate Receptors Proteins 0.000 claims description 39
- 125000003545 alkoxy group Chemical group 0.000 claims description 34
- 230000002401 inhibitory effect Effects 0.000 claims description 33
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 31
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 31
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 29
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 29
- 229910052757 nitrogen Inorganic materials 0.000 claims description 27
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 24
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- 150000002367 halogens Chemical class 0.000 claims description 21
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- GRBQNAGYLXGQCJ-UHFFFAOYSA-N 2-[amino-(4-methylphenyl)methyl]propanedioic acid Chemical compound CC1=CC=C(C(N)C(C(O)=O)C(O)=O)C=C1 GRBQNAGYLXGQCJ-UHFFFAOYSA-N 0.000 claims description 2
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- OXBZNIRABQKQTO-UHFFFAOYSA-N 3-amino-3-[3-(4-chlorophenoxy)phenyl]propanoic acid Chemical compound OC(=O)CC(N)C1=CC=CC(OC=2C=CC(Cl)=CC=2)=C1 OXBZNIRABQKQTO-UHFFFAOYSA-N 0.000 claims description 2
- JVQPVKJZKRICRR-UHFFFAOYSA-N 3-azaniumyl-3-(4-nitrophenyl)propanoate Chemical compound OC(=O)CC(N)C1=CC=C([N+]([O-])=O)C=C1 JVQPVKJZKRICRR-UHFFFAOYSA-N 0.000 claims description 2
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- ZIYVHBGGAOATLY-UHFFFAOYSA-N methylmalonic acid Chemical compound OC(=O)C(C)C(O)=O ZIYVHBGGAOATLY-UHFFFAOYSA-N 0.000 claims 2
- DOHHGYXZPWMNKT-CQSZACIVSA-N (3r)-3-amino-3-(3-phenoxyphenyl)propanoic acid Chemical compound OC(=O)C[C@@H](N)C1=CC=CC(OC=2C=CC=CC=2)=C1 DOHHGYXZPWMNKT-CQSZACIVSA-N 0.000 claims 1
- INAQBBFMGZBFDK-OAHLLOKOSA-N (3r)-3-amino-3-[3-(4-methylphenoxy)phenyl]propanoic acid Chemical compound C1=CC(C)=CC=C1OC1=CC=CC([C@H](N)CC(O)=O)=C1 INAQBBFMGZBFDK-OAHLLOKOSA-N 0.000 claims 1
- NVKJHUJOTYZSCP-CQSZACIVSA-N (3r)-3-azaniumyl-3-[3-[3-(trifluoromethyl)phenoxy]phenyl]propanoate Chemical compound [O-]C(=O)C[C@@H]([NH3+])C1=CC=CC(OC=2C=C(C=CC=2)C(F)(F)F)=C1 NVKJHUJOTYZSCP-CQSZACIVSA-N 0.000 claims 1
- DOHHGYXZPWMNKT-AWEZNQCLSA-N (3s)-3-amino-3-(3-phenoxyphenyl)propanoic acid Chemical compound OC(=O)C[C@H](N)C1=CC=CC(OC=2C=CC=CC=2)=C1 DOHHGYXZPWMNKT-AWEZNQCLSA-N 0.000 claims 1
- INAQBBFMGZBFDK-HNNXBMFYSA-N (3s)-3-amino-3-[3-(4-methylphenoxy)phenyl]propanoic acid Chemical compound C1=CC(C)=CC=C1OC1=CC=CC([C@@H](N)CC(O)=O)=C1 INAQBBFMGZBFDK-HNNXBMFYSA-N 0.000 claims 1
- UXSWIUULBPJEDJ-ZDUSSCGKSA-N (3s)-3-amino-3-[3-[2-(trifluoromethyl)phenoxy]phenyl]propanoic acid Chemical compound OC(=O)C[C@H](N)C1=CC=CC(OC=2C(=CC=CC=2)C(F)(F)F)=C1 UXSWIUULBPJEDJ-ZDUSSCGKSA-N 0.000 claims 1
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- 206010010904 Convulsion Diseases 0.000 abstract description 83
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- 239000002904 solvent Substances 0.000 description 82
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 71
- 125000000623 heterocyclic group Chemical group 0.000 description 71
- BTCSSZJGUNDROE-UHFFFAOYSA-N gamma-aminobutyric acid Chemical compound NCCCC(O)=O BTCSSZJGUNDROE-UHFFFAOYSA-N 0.000 description 50
- 125000000753 cycloalkyl group Chemical group 0.000 description 49
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 45
- 230000000694 effects Effects 0.000 description 44
- 238000004809 thin layer chromatography Methods 0.000 description 39
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 35
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 34
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 33
- 239000003795 chemical substances by application Substances 0.000 description 32
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| US20040208875A1 (en) * | 1995-03-15 | 2004-10-21 | Queen's University At Kingston | Method for treating amyloidosis |
| JP4726304B2 (ja) * | 1999-04-28 | 2011-07-20 | ベルス ヘルス (インターナショナル) リミティッド | アミロイドーシスを治療するための組成物および方法 |
| EP1237547A2 (en) * | 1999-07-09 | 2002-09-11 | Isis Innovation Limited | Compounds for inhibiting diseases and preparing cells for transplantation |
| US8329924B2 (en) * | 2001-06-11 | 2012-12-11 | Vertex Pharmaceuticals (Canada) Incorporated | Compounds and methods for the treatment or prevention of Flavivirus infections |
| EA007484B1 (ru) * | 2001-06-11 | 2006-10-27 | Вирокем Фарма Инк. | Соединения и способы лечения или предупреждения инфекций flavivirus |
| US7355042B2 (en) | 2001-10-16 | 2008-04-08 | Hypnion, Inc. | Treatment of CNS disorders using CNS target modulators |
| NI200300043A (es) * | 2002-03-28 | 2003-11-05 | Warner Lambert Co | AMINOACIDOS CON AFINIDAD POR LA PROTEINA a2DELTA. |
| US20070010573A1 (en) | 2003-06-23 | 2007-01-11 | Xianqi Kong | Methods and compositions for treating amyloid-related diseases |
| US7244764B2 (en) | 2003-06-23 | 2007-07-17 | Neurochem (International) Limited | Methods and compositions for treating amyloid-related diseases |
| EP1670452A2 (en) * | 2003-09-25 | 2006-06-21 | Warner-Lambert Company LLC | Method of use of aminoacids having affinity for the a2d protein |
| JP2007538080A (ja) * | 2004-05-17 | 2007-12-27 | オデッサ ファーマ,エルエルシー | α−ケト分岐鎖アミノ酸を用いた脳神経細胞内グルタミン酸レベルの低減 |
| JP5145537B2 (ja) | 2004-12-22 | 2013-02-20 | ビーエイチアイ リミテッド パートナーシップ | アミロイド関連疾患を治療するための方法および組成物 |
| TW200716088A (en) * | 2005-04-15 | 2007-05-01 | Neurochem Int Ltd | Formulations and methods for treating amyloidosis |
| WO2007023389A2 (en) * | 2005-07-21 | 2007-03-01 | Neurochem (International) Limited | Polymorphic forms of 3-amino-1-propanesulfonic acid |
| DE602006016990D1 (de) * | 2005-12-22 | 2010-10-28 | Bellus Health Int Ltd | Behandlung von diabetischer nephropathie |
| JP5607930B2 (ja) | 2006-10-12 | 2014-10-15 | ビーエイチアイ リミテッド パートナーシップ | 3−アミノ−1−プロパンスルホン酸を送達するための方法、化合物、組成物および媒体 |
| WO2008078176A1 (en) * | 2006-12-22 | 2008-07-03 | Bellus Health (International) Limited | Methods, compounds, and compositions for treating metabolic disorders and diabetes |
| WO2009079373A2 (en) * | 2007-12-14 | 2009-06-25 | The Regents Of The University Of California | Inhibitors of calcium-activated chloride channels |
Family Cites Families (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2461842A (en) * | 1943-02-26 | 1949-02-15 | Sharples Chemicals Inc | Condensation of nitriles with amides and the production of beta-alanine |
| NZ194348A (en) * | 1979-07-26 | 1982-09-14 | Merrell Toraude & Co | Fluorinated methyl-beta-alanine derivatives and pharmaceutical compositions |
| US4255448A (en) * | 1979-09-10 | 1981-03-10 | Wisconsin Alumni Research Foundation | Method for reducing epileptiform activity |
| JPS6124552A (ja) * | 1984-07-13 | 1986-02-03 | Kuraray Co Ltd | γ−アミノ酪酸誘導体およびその製造法 |
| US4906779A (en) * | 1986-07-10 | 1990-03-06 | State Of Oregon, Acting By And Through The Oregon State Board Of Higher Education, Acting For And On Behalf Of The Oregon Health Sciences University | N,N'-disubstituted guanidines and their use as excitatory amino acid antagonists |
| DE3737399A1 (de) * | 1987-11-04 | 1989-05-18 | Schwabe Willmar Gmbh & Co | Aminosaeureester, verfahren zu ihrer herstellung und ihre verwendung |
| EP0425669B1 (en) * | 1988-07-18 | 1995-01-25 | Yamasa Shoyu Kabushiki Kaisha also trading as Yamasa Corporation | 1-amino-5-halogenouracils, process for their preparation, and central nervous system depressants containing same as active ingredient |
| GB8926512D0 (en) * | 1989-11-23 | 1990-01-10 | Pfizer Ltd | Therapeutic agents |
| US5648369A (en) * | 1991-11-20 | 1997-07-15 | University Of Kentucky Research Foundation | Aminoalkylpyridine compounds which are useful as anitconvulsant drugs, excitatory amino acid inhibitors and NMDA sigma receptor antagonists |
| US6306909B1 (en) * | 1997-03-12 | 2001-10-23 | Queen's University At Kingston | Anti-epileptogenic agents |
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2002
- 2002-03-13 CN CNA028098706A patent/CN1774635A/zh active Pending
- 2002-03-13 CA CA002440834A patent/CA2440834A1/en not_active Abandoned
- 2002-03-13 JP JP2002572418A patent/JP2004538258A/ja not_active Withdrawn
- 2002-03-13 WO PCT/CA2002/000363 patent/WO2002073208A2/en not_active Ceased
- 2002-03-13 IL IL15784502A patent/IL157845A0/xx unknown
- 2002-03-13 MX MXPA03008164A patent/MXPA03008164A/es not_active Application Discontinuation
- 2002-03-13 EP EP02708078A patent/EP1386166A2/en not_active Withdrawn
- 2002-10-15 US US10/272,249 patent/US20030194375A1/en not_active Abandoned
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2007
- 2007-06-06 JP JP2007150044A patent/JP2007302678A/ja active Pending
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2015157827A (ja) * | 2008-02-07 | 2015-09-03 | マーケット ユニバーシティー | 統合失調症を治療するため及び薬物渇望を低減するためのシステイン及びシスチンプロドラッグ |
Also Published As
| Publication number | Publication date |
|---|---|
| MXPA03008164A (es) | 2003-12-12 |
| WO2002073208A3 (en) | 2003-12-04 |
| CA2440834A1 (en) | 2002-09-19 |
| CN1774635A (zh) | 2006-05-17 |
| US20030194375A1 (en) | 2003-10-16 |
| JP2007302678A (ja) | 2007-11-22 |
| EP1386166A2 (en) | 2004-02-04 |
| IL157845A0 (en) | 2004-03-28 |
| WO2002073208A2 (en) | 2002-09-19 |
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