JP2002541215A5 - - Google Patents
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- Publication number
- JP2002541215A5 JP2002541215A5 JP2000610520A JP2000610520A JP2002541215A5 JP 2002541215 A5 JP2002541215 A5 JP 2002541215A5 JP 2000610520 A JP2000610520 A JP 2000610520A JP 2000610520 A JP2000610520 A JP 2000610520A JP 2002541215 A5 JP2002541215 A5 JP 2002541215A5
- Authority
- JP
- Japan
- Prior art keywords
- gabapentin
- pain
- reagent
- sodium channel
- pregabalin
- Prior art date
- 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.)
- Pending
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- 208000002193 Pain Diseases 0.000 description 67
- 239000003153 chemical reaction reagent Substances 0.000 description 66
- 150000001875 compounds Chemical class 0.000 description 58
- 239000003195 sodium channel blocking agent Substances 0.000 description 57
- 229960002870 gabapentin Drugs 0.000 description 55
- 208000000094 Chronic Pain Diseases 0.000 description 40
- AYXYPKUFHZROOJ-ZETCQYMHSA-N pregabalin Chemical compound CC(C)C[C@H](CN)CC(O)=O AYXYPKUFHZROOJ-ZETCQYMHSA-N 0.000 description 38
- 229960001233 pregabalin Drugs 0.000 description 38
- 150000003839 salts Chemical class 0.000 description 35
- 229940125794 sodium channel blocker Drugs 0.000 description 35
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- 239000008194 pharmaceutical composition Substances 0.000 description 27
- 238000000034 method Methods 0.000 description 25
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- 150000002431 hydrogen Chemical class 0.000 description 23
- 206010010904 Convulsion Diseases 0.000 description 22
- 108091006146 Channels Proteins 0.000 description 21
- 125000003118 aryl group Chemical group 0.000 description 19
- 125000000217 alkyl group Chemical group 0.000 description 18
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- 125000002768 hydroxyalkyl group Chemical group 0.000 description 13
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| DK1169060T3 (da) * | 1999-04-09 | 2006-01-16 | Euro Celtique Sa | Natriumkanalblokkerpræparater og anvendelse deraf |
| US7164034B2 (en) | 1999-06-10 | 2007-01-16 | Pfizer Inc. | Alpha2delta ligands for fibromyalgia and other disorders |
| US20080207755A1 (en) * | 2000-05-31 | 2008-08-28 | Pfizer Inc | Alpha 2 Delta Ligands For Fibromyalgia and Other Disorders |
| DK1423168T3 (da) | 2001-09-03 | 2006-05-15 | Newron Pharm Spa | Farmaceutisk præparat omfattende gabapentin eller en analog deraf og et alfa-aminoamid og dets analgetiske anvendelse |
| US20030124174A1 (en) * | 2001-10-25 | 2003-07-03 | Endo Pharmaceuticals, Inc | Method for treating non-neuropathic pain |
| BRPI0200751B1 (pt) * | 2002-02-06 | 2018-10-23 | Univ Minas Gerais | complexos de inclusão de benzaldeído semicabazona em ciclodextrinas e seu método de preparação |
| CA2474751A1 (en) | 2002-02-25 | 2003-09-04 | Vanderbilt University | Expression system for human brain-specific voltage-gated sodium channel, type 1 |
| NZ540591A (en) * | 2002-12-13 | 2008-03-28 | Warner Lambert Co | Pregabalin derivatives for the treatment of fibromyalgia and other disorders |
| EP1438956A1 (en) * | 2003-01-16 | 2004-07-21 | Newron Pharmaceuticals S.p.A. | Alpha-aminoamide derivatives useful as antimigraine agents |
| DE10332487A1 (de) * | 2003-07-16 | 2005-02-10 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Ambroxol für die Behandlung von chronisch nozizeptiven Schmerzen |
| DE10359335A1 (de) * | 2003-10-23 | 2005-05-25 | Viatris Gmbh & Co. Kg | Kombinationen aus Kaliumkanalöffnern und Natriumkanalinhibitoren oder Natriumkanal beeinflussenden Wirkstoffen zur Behandlung von Schmerzzuständen |
| US20050112183A1 (en) * | 2003-11-25 | 2005-05-26 | Galer Bradley S. | Compositions and methods for treating neuropathic sensory loss |
| US20050209319A1 (en) * | 2004-03-18 | 2005-09-22 | Xenoport, Inc. | Treatment of local pain |
| ITMI20041447A1 (it) * | 2004-07-20 | 2004-10-20 | Zambon Spa | Composizione farmaceutica comprendente gabapentina |
| US8410149B2 (en) | 2004-12-06 | 2013-04-02 | Siga Technologies Inc. | Sulfonyl semicarbazides, semicarbazides and ureas, pharmaceutical compositions thereof, and methods for treating hemorrhagic fever viruses, including infections associated with arenaviruses |
| AU2005314252B2 (en) | 2004-12-06 | 2012-09-27 | Siga Technologies, Inc. | Compounds and methods for treating hemorrhagic fever viruses |
| US7994221B2 (en) | 2004-12-06 | 2011-08-09 | Siga Technologies, Inc. | Sulfonyl semicarbazides, carbonyl semicarbazides, semicarbazides and ureas, pharmaceutical compositions thereof, and methods for treating hemorrhagic fever viruses, including infections associated with arenaviruses |
| US20060252745A1 (en) * | 2005-05-06 | 2006-11-09 | Almeida Jose L D | Methods of preparing pharmaceutical compositions comprising eslicarbazepine acetate and methods of use |
| EP1963280B1 (en) | 2005-12-22 | 2015-10-28 | Newron Pharmaceuticals S.p.A. | 2-phenylethylamino derivatives as calcium and/or sodium channel modulators |
| GB0603008D0 (en) * | 2006-02-14 | 2006-03-29 | Portela & Ca Sa | Method |
| WO2007120485A2 (en) * | 2006-03-30 | 2007-10-25 | Cinergen, Llc | Methods of treating pain with alkylxanthines and antiepileptics and compositions for use therefor |
| US20080161393A1 (en) * | 2006-12-08 | 2008-07-03 | Barrett Ronald W | Use of prodrugs of GABA analogs for treating disease |
| GB0700773D0 (en) | 2007-01-15 | 2007-02-21 | Portela & Ca Sa | Drug therapies |
| CN101034257B (zh) * | 2007-04-06 | 2010-09-08 | 上海复旦天臣新技术有限公司 | 用于全息记录的感光薄膜及其制备方法 |
| US20100249238A1 (en) * | 2007-07-02 | 2010-09-30 | Ruben Dario Sinisterra | Pharmaceutical compositions comprising semicarbazones and thiosemicarbazones and method for treating inflammatory, painful and febrile conditions and preventing signs and symptoms of inflammation |
| RS55769B1 (sr) * | 2007-11-23 | 2017-07-31 | Gruenenthal Gmbh | Kompozicije tapentadola |
| SG157299A1 (en) | 2008-05-09 | 2009-12-29 | Agency Science Tech & Res | Diagnosis and treatment of kawasaki disease |
| US8975233B2 (en) * | 2010-01-26 | 2015-03-10 | Northwind Medical, Inc. | Methods for renal denervation |
| JP2013531687A (ja) | 2010-07-16 | 2013-08-08 | パーデュー、ファーマ、リミテッド、パートナーシップ | ナトリウムチャネル遮断剤としてのピリジン化合物 |
| AU2011303597A1 (en) | 2010-09-17 | 2013-04-11 | Purdue Pharma L.P. | Pyridine compounds and the uses thereof |
| KR20130095772A (ko) | 2010-10-05 | 2013-08-28 | 퍼듀 퍼머 엘피 | 나트륨 채널 차단제로서 퀴나졸린 화합물 |
| US20130189354A1 (en) * | 2010-10-07 | 2013-07-25 | Trinity Laboratories, Inc., | Novel Pharmaceutical Compositions for Treating Chronic Pain and Pain Associated with Neuropathy |
| EP2655330B1 (en) | 2010-12-22 | 2016-02-10 | Purdue Pharma LP | Substituted pyridines as sodium channel blockers |
| EP3255041A1 (en) | 2011-09-02 | 2017-12-13 | Purdue Pharma L.P. | Pyrimidines as sodium channel blockers |
| WO2013064883A1 (en) | 2011-10-31 | 2013-05-10 | Purdue Pharma L.P. | Heteroaryl compounds as sodium channel blockers |
| WO2013064884A1 (en) | 2011-10-31 | 2013-05-10 | Purdue Pharma L.P. | Quaternized amines as sodium channel blockers |
| US9133131B2 (en) | 2011-11-15 | 2015-09-15 | Purdue Pharma L.P. | Pyrimidine diol amides as sodium channel blockers |
| WO2013136170A1 (en) | 2012-03-16 | 2013-09-19 | Purdue Pharma L.P. | Substituted pyridines as sodium channel blockers |
| EP2935257B1 (en) | 2012-12-20 | 2018-02-07 | Purdue Pharma LP | Cyclic sulfonamides as sodium channel blockers |
| ES2961655T3 (es) * | 2013-01-18 | 2024-03-13 | Kemphys Ltd | Medicamento para tratamiento de enfermedad neuropática |
| US9120786B2 (en) | 2013-03-04 | 2015-09-01 | Purdue Pharma, L.P. | Triazine carboxamides as sodium channel blockers |
| WO2014135955A1 (en) | 2013-03-04 | 2014-09-12 | Purdue Pharma L.P. | Pyrimidine carboxamides as sodium channel blockers |
| CA2939549C (en) | 2013-03-15 | 2020-08-18 | Purdue Pharma L.P. | Carboxamide derivatives and use thereof |
| CN105612152A (zh) | 2013-08-26 | 2016-05-25 | 普渡制药公司 | 氮杂螺[4.5]癸烷衍生物及其用途 |
| US9359330B2 (en) | 2013-08-26 | 2016-06-07 | Purdue Pharma L.P. | Substituted piperidines as sodium channel blockers |
| US9828348B2 (en) | 2013-11-08 | 2017-11-28 | Purdue Pharma L.P. | Benzimidazole derivatives and use thereof |
| US9340504B2 (en) | 2013-11-21 | 2016-05-17 | Purdue Pharma L.P. | Pyridine and piperidine derivatives as novel sodium channel blockers |
| US9745287B2 (en) | 2013-12-20 | 2017-08-29 | Purdue Pharma L.P. | Pyrimidines and use thereof |
| US9695144B2 (en) | 2013-12-23 | 2017-07-04 | Purdue Pharma L.P. | Dibenzazepine derivatives and use thereof |
| JP6337124B2 (ja) | 2013-12-23 | 2018-06-06 | パーデュー、ファーマ、リミテッド、パートナーシップ | インダゾール及びその使用 |
| EP3089978B1 (en) | 2013-12-30 | 2018-08-29 | Purdue Pharma L.P. | Pyridone-sulfone morphinan analogs as opioid receptor ligands |
| JP6526023B2 (ja) | 2014-01-24 | 2019-06-05 | パーデュー、ファーマ、リミテッド、パートナーシップ | ピリジン類及びピリミジン類並びにその使用 |
| AU2015217185B2 (en) | 2014-02-12 | 2018-04-05 | Purdue Pharma L.P. | Isoquinoline derivatives and use thereof |
| US10730866B2 (en) | 2014-04-07 | 2020-08-04 | Purdue Pharma L.P. | Indole derivatives and use thereof |
| CA2948144A1 (en) | 2014-05-06 | 2015-11-12 | Purdue Pharma L.P. | Benzomorphan analogs and use thereof |
| WO2015192039A1 (en) | 2014-06-13 | 2015-12-17 | Purdue Pharma L.P. | Heterocyclic morphinan derivatives and use thereof |
| MA40171A (fr) | 2014-06-13 | 2017-04-19 | Purdue Pharma Lp | Dérivés d'azamophinan et leur utilisation |
| EP3265074B1 (en) * | 2015-03-03 | 2020-08-12 | ARK Diagnostics, Inc. | Pregabalin immunoassays |
| WO2018125716A1 (en) | 2017-01-02 | 2018-07-05 | Purdue Pharma L.P. | Morphinan derivatives and use thereof |
| WO2022183051A1 (en) * | 2021-02-26 | 2022-09-01 | Vyluma Inc. | Methods and formulations for topical administration of gabapentinoids |
| CN115554293A (zh) * | 2021-07-01 | 2023-01-03 | 南京宁丹新药技术有限公司 | 一种药物组合物及其用途 |
Family Cites Families (46)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US549692A (en) * | 1895-11-12 | And albert s | ||
| 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 |
| DK153787C (da) * | 1979-06-01 | 1989-01-16 | Wellcome Found | Analogifremgangsmaade til fremstilling af substituerede 3,5-diamino-6-phenyl-1,2,4-triaziner og alfa-cyanobenzyliden-aminoguanidinforbindelser til anvendelse som mellemprodukter herved |
| US4894476A (en) * | 1988-05-02 | 1990-01-16 | Warner-Lambert Company | Gabapentin monohydrate and a process for producing the same |
| FR2639225B1 (fr) * | 1988-11-21 | 1993-05-21 | Centre Nat Rech Scient | Compositions pharmaceutiques pour la neuroprotection contenant des arylcyclohexylamines |
| IL94466A (en) * | 1989-05-25 | 1995-01-24 | Erba Carlo Spa | Pharmaceutical preparations containing the history of A-amino carboxamide N-phenylalkyl are converted into such new compounds and their preparation |
| US5025035A (en) * | 1990-10-12 | 1991-06-18 | Warner-Lambert Company | Method of treating depression |
| GB9203483D0 (en) * | 1992-02-19 | 1992-04-08 | Wellcome Found | Anti-inflammatory compounds |
| US5330515A (en) * | 1992-06-17 | 1994-07-19 | Cyberonics, Inc. | Treatment of pain by vagal afferent stimulation |
| US5256669A (en) * | 1992-08-07 | 1993-10-26 | Aminotek Sciences, Inc. | Methods and compositions for treating acute or chronic pain and drug addiction |
| GB9306886D0 (en) * | 1993-04-01 | 1993-05-26 | Erba Carlo Spa | Substituted (arylakoxybenzyl) aminopropanamide derivatives and process for their preparation |
| GB9306899D0 (en) * | 1993-04-01 | 1993-05-26 | Erba Carlo Spa | Substituted (arylalkylaminobenzyl) aminopropionamide derivatives and process for their preparation |
| ZA953078B (en) * | 1994-04-28 | 1996-01-05 | Alza Corp | Effective therapy for epilepsies |
| GB9426102D0 (en) * | 1994-12-23 | 1995-02-22 | Merck Sharp & Dohme | Pharmacuetical compositions |
| US5741818A (en) * | 1995-06-07 | 1998-04-21 | University Of Saskatchewan | Semicarbazones having CNS activity and pharmaceutical preparations containing same |
| GB9512854D0 (en) * | 1995-06-23 | 1995-08-23 | Wellcome Found | Novel formulation |
| US5795864A (en) * | 1995-06-27 | 1998-08-18 | Neurex Corporation | Stable omega conopetide formulations |
| GB9515412D0 (en) | 1995-07-27 | 1995-09-27 | Pharmacia Spa | 2-(4-substituted)-benzylamino-2-methyl-propanamide derivatives |
| WO1998007447A1 (en) * | 1996-08-23 | 1998-02-26 | Algos Pharmaceutical Corporation | Anticonvulsant containing composition for treating neuropathic pain |
| ATE234298T1 (de) | 1996-08-29 | 2003-03-15 | Takeda Chemical Industries Ltd | Zyklische etherverbindungen als natriumkanal- modulatoren |
| US6290986B1 (en) * | 1996-10-24 | 2001-09-18 | Pharmaceutical Applications Associates, Llc | Method and composition for transdermal administration of pharmacologic agents |
| EP1829539A3 (en) | 1996-11-05 | 2008-02-20 | HEADEXPLORER ApS | A method for treating tension-type headache |
| FR2756738B1 (fr) * | 1996-12-06 | 1999-02-12 | Sod Conseils Rech Applic | Nouvelle application therapeutique d'un derive de la thienylcyclohexylamine |
| US6207685B1 (en) * | 1996-12-06 | 2001-03-27 | Societe De Conseils De Recherches Et D'applications Scientifiques (S.C.R.A.S.) | Therapeutic application of a thienycyclohexylamine derivative |
| IL119890A (en) | 1996-12-24 | 2002-03-10 | Teva Pharma | Gabapentin form iii and preparation of gabapentin form ii |
| GB9706730D0 (en) | 1997-04-03 | 1997-05-21 | Pharmacia & Upjohn Spa | 2-[(3-substituted)-5-Isoxazolymethylaminojalkanamid derivatives |
| NZ500590A (en) * | 1997-04-22 | 2001-11-30 | Cocensys Inc | Carbocyclic and heterocyclic substituted semicarbazones and thiosemicarbazones and the use thereof |
| WO1999008670A1 (en) * | 1997-08-20 | 1999-02-25 | Guglietta, Antonio | Gaba analogs to prevent and treat gastrointestinal damage |
| US5942530A (en) * | 1997-08-28 | 1999-08-24 | Eli Lilly And Company | Method for treating pain |
| JP3782935B2 (ja) * | 1997-09-08 | 2006-06-07 | ワーナー−ランバート・カンパニー、リミテッド、ライアビリティ、カンパニー | 抗癲癇化合物を含有する鎮痛剤組成物およびその使用方法 |
| EP1032377B1 (en) | 1997-11-21 | 2010-11-17 | Purdue Neuroscience Company | Substituted 2-aminoacetamides and the use thereof |
| DE19802327A1 (de) | 1998-01-23 | 1999-07-29 | Goedecke Ag | Synergistische Arzneimittelzubereitung mit analgetischer Wirkung |
| AU2463099A (en) | 1998-01-23 | 1999-08-09 | Warner-Lambert Company | Gabapentin and its derivatives for the treatment of muscular and skeletal pain |
| US5905069A (en) * | 1998-01-26 | 1999-05-18 | The General Hospital Corporation | Methods of decreasing or preventing pain using spicamycin or derivatives thereof |
| EP1058550A4 (en) | 1998-02-04 | 2002-12-18 | Euro Celtique Sa | SUBSTITUTED SEMICARBAZIDES AND THEIR USE |
| GB9804885D0 (en) | 1998-03-06 | 1998-04-29 | Merck Sharp & Dohme | Therapeutic combination |
| ES2137137B1 (es) | 1998-05-25 | 2000-08-16 | Medichem Sa | Nuevo polimorfo de gabapentina no hidratada, su procedimiento de obtencion y su utilizacion para la obtencion de gabapentina de calidad farmaceutica. |
| DE69921137T2 (de) | 1998-07-09 | 2006-02-02 | Warner-Lambert Co. Llc | Pharmazeutische zusammensetzungen enthaltend gaba-analogen und ein antivirales mittel zur behandlung von herpes zoster |
| EP1094817A1 (en) * | 1998-07-09 | 2001-05-02 | Warner-Lambert Company | Compositions comprising gaba analogs and caffeine |
| US6281211B1 (en) * | 1999-02-04 | 2001-08-28 | Euro-Celtique S.A. | Substituted semicarbazides and the use thereof |
| TW502019B (en) * | 1999-03-26 | 2002-09-11 | Cocensys Inc | Aryl substituted pyrazoles, imidazoles, oxazoles, thiazoles and pyrroles, and the use thereof |
| DK1169060T3 (da) * | 1999-04-09 | 2006-01-16 | Euro Celtique Sa | Natriumkanalblokkerpræparater og anvendelse deraf |
| EP1200086A4 (en) * | 1999-08-04 | 2009-05-27 | Icagen Inc | THERAPEUTIC OR PROPHYLACTIC METHODS OF PAIN AND ANXIETY |
| US6113915A (en) * | 1999-10-12 | 2000-09-05 | Allergan Sales, Inc. | Methods for treating pain |
| DK1423168T3 (da) | 2001-09-03 | 2006-05-15 | Newron Pharm Spa | Farmaceutisk præparat omfattende gabapentin eller en analog deraf og et alfa-aminoamid og dets analgetiske anvendelse |
-
2000
- 2000-04-10 DK DK00923183T patent/DK1169060T3/da active
- 2000-04-10 DE DE60022333T patent/DE60022333T2/de not_active Expired - Lifetime
- 2000-04-10 AU AU43349/00A patent/AU4334900A/en not_active Abandoned
- 2000-04-10 JP JP2000610520A patent/JP2002541215A/ja active Pending
- 2000-04-10 WO PCT/US2000/009387 patent/WO2000061188A1/en not_active Ceased
- 2000-04-10 CA CA002370030A patent/CA2370030C/en not_active Expired - Fee Related
- 2000-04-10 EP EP00923183A patent/EP1169060B1/en not_active Expired - Lifetime
- 2000-04-10 AT AT00923183T patent/ATE303162T1/de active
-
2001
- 2001-10-05 US US09/971,007 patent/US20020037926A1/en not_active Abandoned
-
2003
- 2003-08-21 US US10/644,783 patent/US7393872B2/en not_active Expired - Lifetime
-
2008
- 2008-06-13 US US12/138,568 patent/US20080318932A1/en not_active Abandoned
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