JP3632191B2 - 医薬製剤としての２環式アミノ酸 - Google Patents
医薬製剤としての２環式アミノ酸 Download PDFInfo
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- JP3632191B2 JP3632191B2 JP2001531783A JP2001531783A JP3632191B2 JP 3632191 B2 JP3632191 B2 JP 3632191B2 JP 2001531783 A JP2001531783 A JP 2001531783A JP 2001531783 A JP2001531783 A JP 2001531783A JP 3632191 B2 JP3632191 B2 JP 3632191B2
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- Prior art keywords
- aminomethyl
- acetic acid
- mixture
- mmol
- compound
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- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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- -1 Bicyclic amino acids Chemical class 0.000 title claims description 49
- 239000008194 pharmaceutical composition Substances 0.000 title claims description 5
- QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 108
- 150000001875 compounds Chemical class 0.000 claims description 103
- 239000003814 drug Substances 0.000 claims description 33
- 150000003839 salts Chemical class 0.000 claims description 28
- 208000002193 Pain Diseases 0.000 claims description 24
- 230000036407 pain Effects 0.000 claims description 20
- 238000004519 manufacturing process Methods 0.000 claims description 11
- 208000019901 Anxiety disease Diseases 0.000 claims description 9
- 230000036506 anxiety Effects 0.000 claims description 8
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 6
- 206010015037 epilepsy Diseases 0.000 claims description 6
- 230000004770 neurodegeneration Effects 0.000 claims description 6
- 208000015122 neurodegenerative disease Diseases 0.000 claims description 6
- 201000010099 disease Diseases 0.000 claims description 5
- 208000020401 Depressive disease Diseases 0.000 claims description 4
- 208000004296 neuralgia Diseases 0.000 claims description 4
- 230000002981 neuropathic effect Effects 0.000 claims description 4
- 206010042772 syncope Diseases 0.000 claims description 4
- 208000021245 head disease Diseases 0.000 claims description 3
- 208000021722 neuropathic pain Diseases 0.000 claims description 3
- 206010036618 Premenstrual syndrome Diseases 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- 230000003483 hypokinetic effect Effects 0.000 claims 1
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 140
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 120
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 104
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 102
- 239000000203 mixture Substances 0.000 description 96
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- 239000002904 solvent Substances 0.000 description 73
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- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 57
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- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 50
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- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 27
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- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 24
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- 238000000034 method Methods 0.000 description 23
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- 229910004298 SiO 2 Inorganic materials 0.000 description 18
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 18
- UGJMXCAKCUNAIE-UHFFFAOYSA-N Gabapentin Chemical compound OC(=O)CC1(CN)CCCCC1 UGJMXCAKCUNAIE-UHFFFAOYSA-N 0.000 description 17
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- 229910052786 argon Inorganic materials 0.000 description 16
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- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 14
- 239000012230 colorless oil Substances 0.000 description 14
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 13
- 239000003054 catalyst Substances 0.000 description 13
- ONKWZNBXHSMMDK-UHFFFAOYSA-N 2-[2-(aminomethyl)-1,3,3a,4,5,6,7,7a-octahydroinden-2-yl]acetic acid Chemical compound C1CCCC2CC(CN)(CC(O)=O)CC21 ONKWZNBXHSMMDK-UHFFFAOYSA-N 0.000 description 12
- 206010010904 Convulsion Diseases 0.000 description 12
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 12
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- 239000002253 acid Substances 0.000 description 12
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 12
- NDDZVQRQVFTNSN-UHFFFAOYSA-N 2-[3-(aminomethyl)-3-bicyclo[3.2.0]heptanyl]acetic acid Chemical compound C1C(CN)(CC(O)=O)CC2CCC21 NDDZVQRQVFTNSN-UHFFFAOYSA-N 0.000 description 11
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 11
- 239000003921 oil Substances 0.000 description 11
- 235000019198 oils Nutrition 0.000 description 11
- GSBZRDSCOPXLJJ-UHFFFAOYSA-N 2-[2-(aminomethyl)-3,3a,4,5,6,6a-hexahydro-1h-pentalen-2-yl]acetic acid Chemical compound C1CCC2CC(CN)(CC(O)=O)CC21 GSBZRDSCOPXLJJ-UHFFFAOYSA-N 0.000 description 10
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 10
- 241001465754 Metazoa Species 0.000 description 10
- 239000002585 base Substances 0.000 description 10
- 239000000725 suspension Substances 0.000 description 10
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical class [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 9
- QMMFVYPAHWMCMS-UHFFFAOYSA-N Dimethyl sulfide Chemical compound CSC QMMFVYPAHWMCMS-UHFFFAOYSA-N 0.000 description 9
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 9
- 235000011054 acetic acid Nutrition 0.000 description 9
- 150000001732 carboxylic acid derivatives Chemical group 0.000 description 9
- MTHSVFCYNBDYFN-UHFFFAOYSA-N diethylene glycol Chemical compound OCCOCCO MTHSVFCYNBDYFN-UHFFFAOYSA-N 0.000 description 9
- 150000003951 lactams Chemical class 0.000 description 9
- 238000002360 preparation method Methods 0.000 description 9
- 239000000651 prodrug Substances 0.000 description 9
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- 239000000126 substance Substances 0.000 description 9
- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 9
- JKONURJHZJCUAD-UHFFFAOYSA-N 2-[2-(aminomethyl)-3,3a,4,5,6,7,8,8a-octahydro-1h-azulen-2-yl]acetic acid Chemical compound C1CCCCC2CC(CN)(CC(O)=O)CC21 JKONURJHZJCUAD-UHFFFAOYSA-N 0.000 description 8
- HZROAXDCVPLQAB-UHFFFAOYSA-N 2-[3-(aminomethyl)-3-bicyclo[3.1.0]hexanyl]acetic acid Chemical compound C1C(CN)(CC(O)=O)CC2CC21 HZROAXDCVPLQAB-UHFFFAOYSA-N 0.000 description 8
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 8
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 8
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- DEQYTNZJHKPYEZ-UHFFFAOYSA-N ethyl acetate;heptane Chemical compound CCOC(C)=O.CCCCCCC DEQYTNZJHKPYEZ-UHFFFAOYSA-N 0.000 description 8
- BTCSSZJGUNDROE-UHFFFAOYSA-N gamma-aminobutyric acid Chemical compound NCCCC(O)=O BTCSSZJGUNDROE-UHFFFAOYSA-N 0.000 description 8
- 239000001257 hydrogen Substances 0.000 description 8
- 229910052739 hydrogen Inorganic materials 0.000 description 8
- LYGJENNIWJXYER-UHFFFAOYSA-N nitromethane Chemical compound C[N+]([O-])=O LYGJENNIWJXYER-UHFFFAOYSA-N 0.000 description 8
- 239000012044 organic layer Substances 0.000 description 8
- 239000003826 tablet Substances 0.000 description 8
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- SGUVLZREKBPKCE-UHFFFAOYSA-N 1,5-diazabicyclo[4.3.0]-non-5-ene Chemical compound C1CCN=C2CCCN21 SGUVLZREKBPKCE-UHFFFAOYSA-N 0.000 description 6
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- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 6
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- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 6
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- 229910000104 sodium hydride Inorganic materials 0.000 description 6
- JQWHASGSAFIOCM-UHFFFAOYSA-M sodium periodate Chemical compound [Na+].[O-]I(=O)(=O)=O JQWHASGSAFIOCM-UHFFFAOYSA-M 0.000 description 6
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- C07C2602/20—All rings being cycloaliphatic the ring system containing seven carbon atoms
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- C07C2602/00—Systems containing two condensed rings
- C07C2602/02—Systems containing two condensed rings the rings having only two atoms in common
- C07C2602/14—All rings being cycloaliphatic
- C07C2602/22—All rings being cycloaliphatic the ring system containing eight carbon atoms, e.g. pentalene
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- C07C2602/00—Systems containing two condensed rings
- C07C2602/02—Systems containing two condensed rings the rings having only two atoms in common
- C07C2602/14—All rings being cycloaliphatic
- C07C2602/24—All rings being cycloaliphatic the ring system containing nine carbon atoms, e.g. perhydroindane
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
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- C07C2602/00—Systems containing two condensed rings
- C07C2602/02—Systems containing two condensed rings the rings having only two atoms in common
- C07C2602/14—All rings being cycloaliphatic
- C07C2602/26—All rings being cycloaliphatic the ring system containing ten carbon atoms
- C07C2602/28—Hydrogenated naphthalenes
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Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US16072599P | 1999-10-20 | 1999-10-20 | |
| US60/160,725 | 1999-10-20 | ||
| PCT/US2000/028687 WO2001028978A1 (en) | 1999-10-20 | 2000-10-17 | Bicyclic amino acids as pharmaceutical agents |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2004266488A Division JP3744928B2 (ja) | 1999-10-20 | 2004-09-14 | 医薬製剤としての２環式アミノ酸 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2003512348A JP2003512348A (ja) | 2003-04-02 |
| JP3632191B2 true JP3632191B2 (ja) | 2005-03-23 |
| JP2003512348A5 JP2003512348A5 (enExample) | 2005-12-22 |
Family
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Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2001531783A Expired - Fee Related JP3632191B2 (ja) | 1999-10-20 | 2000-10-17 | 医薬製剤としての２環式アミノ酸 |
| JP2004266488A Expired - Fee Related JP3744928B2 (ja) | 1999-10-20 | 2004-09-14 | 医薬製剤としての２環式アミノ酸 |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2004266488A Expired - Fee Related JP3744928B2 (ja) | 1999-10-20 | 2004-09-14 | 医薬製剤としての２環式アミノ酸 |
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Families Citing this family (38)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7164034B2 (en) | 1999-06-10 | 2007-01-16 | Pfizer Inc. | Alpha2delta ligands for fibromyalgia and other disorders |
| NZ522480A (en) * | 2000-06-26 | 2005-06-24 | Warner Lambert Co | Gabapentin analogues for sleep disorders |
| US6620829B2 (en) | 2000-10-17 | 2003-09-16 | Warner-Lambert Company | Method of treating noninflammatory cartilage damage |
| EP1226820A1 (en) | 2001-01-26 | 2002-07-31 | Warner-Lambert Company | Use of bicyclic amino acids for preventing and treating visceral pain and gastrointestinal disorders |
| CA2444053C (en) * | 2001-04-19 | 2008-06-17 | Warner-Lambert Company Llc | Fused bicyclic or tricyclic amino acids |
| GB2375109A (en) * | 2001-05-04 | 2002-11-06 | Warner Lambert Co | Process for preparing bicyclic amino acid |
| GB2375108A (en) * | 2001-05-04 | 2002-11-06 | Warner Lambert Co | Production of a bicycloheptanone |
| US6818787B2 (en) | 2001-06-11 | 2004-11-16 | Xenoport, Inc. | Prodrugs of GABA analogs, compositions and uses thereof |
| US7232924B2 (en) | 2001-06-11 | 2007-06-19 | Xenoport, Inc. | Methods for synthesis of acyloxyalkyl derivatives of GABA analogs |
| AU2002310409C1 (en) * | 2001-06-11 | 2008-04-17 | Xenoport, Inc. | Orally administered dosage forms of GABA analog prodrugs having reduced toxicity |
| US8048917B2 (en) | 2005-04-06 | 2011-11-01 | Xenoport, Inc. | Prodrugs of GABA analogs, compositions and uses thereof |
| US7186855B2 (en) | 2001-06-11 | 2007-03-06 | Xenoport, Inc. | Prodrugs of GABA analogs, compositions and uses thereof |
| PL371944A1 (en) | 2002-01-31 | 2005-07-11 | Warner-Lambert Company Llc | Alpha 2 delta ligands to treat tinnitus |
| RU2286151C2 (ru) * | 2002-02-22 | 2006-10-27 | Уорнер-Ламберт Компани Ллс | Комбинации альфа-2-дельта-лиганда с селективным ингибитором циклооксигеназы-2 |
| JP2005534678A (ja) * | 2002-06-27 | 2005-11-17 | ワーナー−ランバート カンパニー リミティド ライアビリティー カンパニー | 注意欠陥多動性障害の治療方法 |
| US7419981B2 (en) | 2002-08-15 | 2008-09-02 | Pfizer Inc. | Synergistic combinations of an alpha-2-delta ligand and a cGMP phosphodieterse 5 inhibitor |
| GB0219024D0 (en) * | 2002-08-15 | 2002-09-25 | Pfizer Ltd | Synergistic combinations |
| BR0313432A (pt) * | 2002-08-15 | 2005-07-12 | Pfizer | Uso terapêutico de aminoácidos bicìclicos ou tricìclicos fundidos |
| GB0223072D0 (en) | 2002-10-04 | 2002-11-13 | Pfizer Ltd | Cyclic nitromethyl acetic acid derivatives |
| US7018818B2 (en) | 2002-10-04 | 2006-03-28 | Pfizer Inc. | Intermediates in the preparation of therapeutic fused bicyclic amino acids |
| AU2003297927A1 (en) | 2002-12-11 | 2004-06-30 | Xenoport, Inc. | Prodrugs of fused gaba analogs, pharmaceutical compositions and uses thereof |
| PT1572173E (pt) | 2002-12-13 | 2010-05-10 | Warner Lambert Co | Ligando alfa-2-delta para tratar sintomas do tracto urinário inferior |
| CA2451267A1 (en) | 2002-12-13 | 2004-06-13 | Warner-Lambert Company Llc | Pharmaceutical uses for alpha2delta ligands |
| EP2172197A1 (en) | 2002-12-13 | 2010-04-07 | Warner-Lambert Company LLC | Octanoic acid derivative to treat fibromyalgia and other pains |
| ATE449633T1 (de) | 2003-09-12 | 2009-12-15 | Pfizer | Kombinationen aus alpha-2-delta liganden und serotonin / noradrenalin-wiederaufnahmehemmern |
| WO2006092692A1 (en) * | 2005-03-01 | 2006-09-08 | Pfizer Limited | Use of combinations of pde7 inhibitors and alpha-2-delty ligands for the treatment of neuropathic pain |
| AR061728A1 (es) * | 2006-06-30 | 2008-09-17 | Pfizer Prod Inc | Composicion para tratamiento usando compuestos selectivos alfa-2-delta-1 |
| CN102058885B (zh) | 2006-12-22 | 2013-04-10 | 瑞蔻达蒂爱尔兰有限公司 | 采用α2δ配体和NSAID的下泌尿道疾病的联合治疗 |
| KR101335784B1 (ko) | 2007-09-28 | 2013-12-05 | 다이이찌 산쿄 가부시키가이샤 | 2 고리성 γ-아미노산 유도체 |
| WO2010110361A1 (ja) * | 2009-03-26 | 2010-09-30 | 第一三共株式会社 | 二環性γ－アミノ酸誘導体の製造方法 |
| BR112013031360B1 (pt) | 2011-06-08 | 2022-01-25 | Daiichi Sankyo Company, Limited | Método para produzir um composto |
| ES2649968T3 (es) | 2011-06-08 | 2018-01-16 | Daiichi Sankyo Company, Limited | Procedimiento de producción de un compuesto bicíclico vía transposición de Claisen |
| HUE040225T2 (hu) | 2011-12-15 | 2019-02-28 | Daiichi Sankyo Co Ltd | Eljárás biciklikus vegyület optikai elválasztására aszimmetrikus katalizátort felhasználva |
| HUE033397T2 (en) | 2012-04-10 | 2017-12-28 | Daiichi Sankyo Co Ltd | A method for the optical separation of bicyclic compounds by an enzyme |
| US9066853B2 (en) | 2013-01-15 | 2015-06-30 | Warsaw Orthopedic, Inc. | Clonidine compounds in a biodegradable fiber |
| TWI635071B (zh) | 2013-07-08 | 2018-09-11 | 第一三共股份有限公司 | 光學活性二環γ－胺基酸衍生物及其製造方法 |
| WO2018166855A1 (en) | 2017-03-16 | 2018-09-20 | Basf Se | Heterobicyclic substituted dihydroisoxazoles |
| CN113045410A (zh) * | 2021-03-29 | 2021-06-29 | 华东理工大学 | 一种双环降二萜类化合物及其合成基因及制备方法 |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3641129A (en) | 1969-06-17 | 1972-02-08 | Merck & Co Inc | Antifibrinolytic compounds |
| DE2460891C2 (de) | 1974-12-21 | 1982-09-23 | Gödecke AG, 1000 Berlin | 1-Aminomethyl-1-cycloalkanessigsäuren und deren Ester, Verfahren zu deren Herstellung und diese Verbindungen enthaltende Arzneimittel |
| US4087544A (en) * | 1974-12-21 | 1978-05-02 | Warner-Lambert Company | Treatment of cranial dysfunctions using novel cyclic amino acids |
| ATE323067T1 (de) | 1997-10-27 | 2006-04-15 | Warner Lambert Co | Zyklische aminosäuren und deren derivate als arzneimittel |
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