NO329379B1 - Piperidinderivater samt anvendelse og fremstilling derav og farmasoytisk preparat - Google Patents
Piperidinderivater samt anvendelse og fremstilling derav og farmasoytisk preparat Download PDFInfo
- Publication number
- NO329379B1 NO329379B1 NO20043239A NO20043239A NO329379B1 NO 329379 B1 NO329379 B1 NO 329379B1 NO 20043239 A NO20043239 A NO 20043239A NO 20043239 A NO20043239 A NO 20043239A NO 329379 B1 NO329379 B1 NO 329379B1
- Authority
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- Norway
- Prior art keywords
- solution
- formula
- phenyl
- compound
- hydrogen
- Prior art date
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- 238000002360 preparation method Methods 0.000 title claims description 25
- 239000000825 pharmaceutical preparation Substances 0.000 title claims description 8
- 150000003053 piperidines Chemical class 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims description 205
- 239000000203 mixture Substances 0.000 claims description 108
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 65
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 59
- 229910052757 nitrogen Inorganic materials 0.000 claims description 43
- 229910052739 hydrogen Inorganic materials 0.000 claims description 40
- 239000001257 hydrogen Substances 0.000 claims description 40
- 150000003839 salts Chemical class 0.000 claims description 30
- 238000000034 method Methods 0.000 claims description 29
- 238000006243 chemical reaction Methods 0.000 claims description 18
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 17
- 125000000217 alkyl group Chemical group 0.000 claims description 16
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 16
- 150000002431 hydrogen Chemical group 0.000 claims description 15
- QDZOEBFLNHCSSF-PFFBOGFISA-N (2S)-2-[[(2R)-2-[[(2S)-1-[(2S)-6-amino-2-[[(2S)-1-[(2R)-2-amino-5-carbamimidamidopentanoyl]pyrrolidine-2-carbonyl]amino]hexanoyl]pyrrolidine-2-carbonyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-N-[(2R)-1-[[(2S)-1-[[(2R)-1-[[(2S)-1-[[(2S)-1-amino-4-methyl-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]pentanediamide Chemical compound C([C@@H](C(=O)N[C@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(N)=O)NC(=O)[C@@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CCCCN)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](N)CCCNC(N)=N)C1=CC=CC=C1 QDZOEBFLNHCSSF-PFFBOGFISA-N 0.000 claims description 13
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 13
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- 101800003906 Substance P Proteins 0.000 claims description 13
- 229910052736 halogen Inorganic materials 0.000 claims description 13
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- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 13
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- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 16
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- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 14
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Classifications
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- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
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Landscapes
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- Immunology (AREA)
- Otolaryngology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Hydrogenated Pyridines (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
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| GBGB0203020.3A GB0203020D0 (en) | 2002-02-08 | 2002-02-08 | Chemical compounds |
| PCT/EP2003/001308 WO2003066635A1 (en) | 2002-02-08 | 2003-02-10 | Piperidine derivatives |
Publications (3)
| Publication Number | Publication Date |
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| NO20043239D0 NO20043239D0 (no) | 2004-08-02 |
| NO20043239L NO20043239L (no) | 2004-08-02 |
| NO329379B1 true NO329379B1 (no) | 2010-10-04 |
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| NO20043239A NO329379B1 (no) | 2002-02-08 | 2004-08-02 | Piperidinderivater samt anvendelse og fremstilling derav og farmasoytisk preparat |
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| TWI283241B (en) | 2002-05-29 | 2007-07-01 | Tanabe Seiyaku Co | Novel piperidine compound |
| EP1594574A2 (de) * | 2003-01-27 | 2005-11-16 | Glaxo Group Limited | Nk1-rezeptor-antagonisten zur behandlung der funktionalen dyspepsie |
| GB0308968D0 (en) * | 2003-04-17 | 2003-05-28 | Glaxo Group Ltd | Medicaments |
| US20060030600A1 (en) * | 2004-08-06 | 2006-02-09 | Patrick Schnider | Dual NK1/NK3 receptor antagonists for the treatment of schizophrenia |
| JP5078869B2 (ja) * | 2005-03-08 | 2012-11-21 | ジヤンセン・フアーマシユーチカ・ナームローゼ・フエンノートシヤツプ | ニューロキニン（ｎｋ１）拮抗物質としてのジアザ−スピロ−［４．４］−ノナン誘導体 |
| JP5121716B2 (ja) | 2005-09-09 | 2013-01-16 | グラクソスミスクライン・リミテッド・ライアビリティ・カンパニー | ピリジン誘導体および精神異常の処置におけるそれらの使用 |
| AR057828A1 (es) | 2005-09-29 | 2007-12-19 | Astrazeneca Ab | Compuestos derivados de azetidina, su preparacion y composicion farmaceuutica |
| JP2009523170A (ja) * | 2006-01-11 | 2009-06-18 | メルク エンド カムパニー インコーポレーテッド | 縮合トリアゾールタキキニン受容体アンダニスト |
| US7872022B2 (en) * | 2006-04-03 | 2011-01-18 | Hoffmann-La Roche Inc. | Serotonin transporter (SERT) inhibitors for the treatment of depression and anxiety |
| GB0621229D0 (en) * | 2006-10-20 | 2006-12-06 | Glaxo Group Ltd | Novel use |
| EP2117538A1 (de) | 2007-01-24 | 2009-11-18 | Glaxo Group Limited | Pharmazeutische zusammensetzungen mit 2-methoxy-5- (5-trifluoromethyl-tetrazol-i-yl-benzyl) - (2s-phenyl-piperidin-3s-yl-) |
| AU2008268667A1 (en) * | 2007-06-22 | 2008-12-31 | Merck & Co., Inc. | 6.5-pyrrolopiperidine tachykinin receptor antagonists |
| GB0806652D0 (en) * | 2008-04-11 | 2008-05-14 | Glaxo Group Ltd | Anhydrous crystal form of orvepitant maleate |
| GB0812849D0 (en) * | 2008-07-14 | 2008-08-20 | Glaxo Wellcome Mfg Pte Ltd | Novel compounds |
| GB0814340D0 (en) | 2008-08-05 | 2008-09-10 | Smithkline Beecham Corp | Anhydrous crystol form fo a pyridine derivative |
| ES2672099T3 (es) | 2011-07-04 | 2018-06-12 | Irbm - Science Park S.P.A. | Antagonistas del receptor NK-1 para el tratamiento de la neovascularización corneal |
| RU2631319C2 (ru) * | 2012-02-22 | 2017-09-21 | Лео Фарма А/С | Новые соединения - антагонисты рецептора нейрокинина 1 |
| WO2014057003A1 (en) | 2012-10-11 | 2014-04-17 | Nerre Therapeutics Limited | Novel uses |
| WO2015024203A1 (en) * | 2013-08-20 | 2015-02-26 | Leo Pharma A/S | Novel neurokinin 1 receptor antagonist compounds ii |
| CN105579456A (zh) * | 2013-08-20 | 2016-05-11 | 利奥制药有限公司 | 新型神经激肽1受体拮抗剂化合物ii |
| JP6621534B2 (ja) * | 2016-01-08 | 2019-12-18 | ネッレ セラピューティクス リミテッドＮｅｒｒｅ Ｔｈｅｒａｐｅｕｔｉｃｓ Ｌｉｍｉｔｅｄ | 慢性咳の処置のためのオルブピタント |
| BR112019021125A2 (pt) | 2017-04-10 | 2020-05-12 | Chase Therapeutics Corporation | Combinação de antagonista de nk1 e método para tratamento de sinucleinopatias |
| MA49524A (fr) | 2017-06-30 | 2021-05-26 | Chase Therapeutics Corp | Compositions d'antagoniste de nk-1 et méthodes destinées à être utilisées dans le traitement de la dépression |
| MX2022011545A (es) | 2020-04-03 | 2022-11-09 | Nerre Therapeutics Ltd | Un antagonista de receptor de nk-1 para tratar una enfermedad que se selecciona de sepsis, choque septico, síndrome de dificultad respiratoria aguda (ards) 0 síndrome de disfunción orgánica múltiple (mcds). |
| CN115697332A (zh) | 2020-06-02 | 2023-02-03 | 尼尔医疗有限公司 | 用于治疗由肺的机械损伤促进的肺纤维化状况的神经激肽(nk)-1受体拮抗剂 |
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| US4112090A (en) | 1974-05-09 | 1978-09-05 | Toyama Chemical Co., Ltd. | Novel penicillins and cephalosporins and process for producing the same |
| US4219554A (en) | 1974-05-09 | 1980-08-26 | Toyama Chemical Company, Limited | Novel penicillins and cephalosporins and process for producing same |
| IL47168A (en) | 1974-05-09 | 1979-07-25 | Toyama Chemical Co Ltd | Mono or dioxo piperazino(thio)carbonylamino derivatives ofpenicillins and cephalosporins and process for producing the same |
| US4087424A (en) | 1974-05-09 | 1978-05-02 | Toyama Chemical Co., Ltd. | Novel penicillins and cephalosporins and process for producing the same |
| US4327097A (en) | 1974-05-09 | 1982-04-27 | Toyama Chemical Co., Ltd. | Novel penicillins |
| US4379152A (en) | 1974-05-09 | 1983-04-05 | Toyama Chemical Co., Ltd. | Cephalosporins |
| US4410522A (en) | 1974-05-09 | 1983-10-18 | Toyama Chemical Co., Ltd. | Cephalosporins |
| US4110327A (en) | 1974-05-09 | 1978-08-29 | Toyama Chemical Co., Ltd. | 2,3 Diketo-piperazinocarbonylamino alkanoic acids and derivatives |
| NO154582C (no) | 1978-10-20 | 1986-11-05 | Ferrosan Ab | Analogifremgangsmaate for fremstilling av terapeutisk aktive difenyl-dibutylpiperazinkarboksamider. |
| JPS57118587A (en) | 1981-11-26 | 1982-07-23 | Toyama Chem Co Ltd | Novel penicillin |
| KR910009880B1 (ko) | 1983-07-25 | 1991-12-03 | 가부시기가이샤 히다찌세이사꾸쇼 | 인터레이스된 텔레비젼 신호중의 화상의 움직임 검출회로 |
| US5028610A (en) | 1987-03-18 | 1991-07-02 | Sankyo Company Limited | N-benzhydryl-substituted heterocyclic derivatives, their preparation and their use |
| GB8709666D0 (en) | 1987-04-23 | 1987-05-28 | Beecham Group Plc | Compounds |
| GB8713061D0 (en) | 1987-06-04 | 1987-07-08 | Beecham Group Plc | Compounds |
| US5109014A (en) | 1990-12-10 | 1992-04-28 | Jacobson Richard M | N-aryl-3-aryl-4-substituted-2,3,4,5-tetrahydro-1H-pyrazole-1-carboxamides |
| GB9106127D0 (en) | 1991-03-22 | 1991-05-08 | Byrne Charles M | Spread |
| SE9100860D0 (sv) | 1991-03-22 | 1991-03-22 | Kabi Pharmacia Ab | New use |
| MY110227A (en) | 1991-08-12 | 1998-03-31 | Ciba Geigy Ag | 1-acylpiperindine compounds. |
| EP0916346A3 (de) | 1991-09-20 | 2000-12-06 | Glaxo Group Limited | NK-1 Rezeptor Antagonisten und 5HT3 Rezeptor Antagonisten zur Behandlung von Emesis |
| CA2083891A1 (en) | 1991-12-03 | 1993-06-04 | Angus Murray Macleod | Heterocyclic compounds, compositions containing them and their use in therapy |
| US5563127A (en) | 1993-03-24 | 1996-10-08 | The Dupont Merck Pharmaceutical Company | Boronic acid and ester inhibitors of thrombin |
| US5348955A (en) | 1993-06-22 | 1994-09-20 | Merck & Co., Inc. | N,N-diacylpiperazines |
| IL111730A (en) | 1993-11-29 | 1998-12-06 | Fujisawa Pharmaceutical Co | Piperazine derivatives, processes for their preparation and pharmaceutical preparations containing them |
| TW385308B (en) | 1994-03-04 | 2000-03-21 | Merck & Co Inc | Prodrugs of morpholine tachykinin receptor antagonists |
| US5464788A (en) | 1994-03-24 | 1995-11-07 | Merck & Co., Inc. | Tocolytic oxytocin receptor antagonists |
| EP0721941A4 (de) | 1994-07-15 | 1996-09-25 | Meiji Seika Co | Neue verbindungen mit aggregations-hemmenden wirkung auf bluttplättchen |
| DE4425146A1 (de) | 1994-07-15 | 1996-01-18 | Basf Ag | Verwendung heterocyclischer Verbindungen |
| WO1996003378A1 (fr) | 1994-07-26 | 1996-02-08 | Sankyo Company, Limited | Derives d'amide n-phenyle et d'uree |
| DE19520499C2 (de) | 1994-09-17 | 2003-06-18 | Boehringer Ingelheim Kg | Neurokinin-Antagonisten, Verfahren zu ihrer Herstellung, diese Verbindungen enthaltende pharmazeutische Zusammensetzungen sowie ihre Verwendung |
| US5696123A (en) | 1994-09-17 | 1997-12-09 | Boehringer Ingelheim Kg | Neurokinin antagonists |
| AU3607895A (en) | 1994-09-30 | 1996-04-26 | Novartis Ag | 1-acyl-4-aliphatylaminopiperidine compounds |
| EP0709375B1 (de) | 1994-10-25 | 2005-05-18 | AstraZeneca AB | Therapeutisch wirksame Heterocyclen |
| US5998444A (en) | 1995-10-24 | 1999-12-07 | Zeneca Ltd. | Piperidinyl compounds as NK1 or NK2 antagonists |
| US5629322A (en) | 1994-11-15 | 1997-05-13 | Merck & Co., Inc. | Cyclic amidine analogs as inhibitors of nitric oxide synthase |
| US5576317A (en) | 1994-12-09 | 1996-11-19 | Pfizer Inc. | NK-1 receptor antagonists and 5HT3 receptor antagonists for the treatment of emesis |
| AU4432496A (en) | 1994-12-23 | 1996-07-19 | Dr. Karl Thomae Gmbh | Piperazine derivatives, medicaments containing the same, their use and process for preparing the same |
| US5700801A (en) | 1994-12-23 | 1997-12-23 | Karl Thomae, Gmbh | Piperazine derivatives, pharmaceutical compositions containing these compounds, their use and processes for preparing them |
| IL117149A0 (en) | 1995-02-23 | 1996-06-18 | Schering Corp | Muscarinic antagonists |
| NZ321575A (en) | 1995-10-30 | 1999-05-28 | Janssen Pharmaceutica Nv | 1-(1,2-disubstituted piperidinyl)-4- substituted piperazine derivatives |
| WO1997016400A1 (en) * | 1995-10-31 | 1997-05-09 | Unichema Chemie B.V. | Process for the deparaffination of squalane |
| TW531537B (en) | 1995-12-27 | 2003-05-11 | Janssen Pharmaceutica Nv | 1-(1,2-disubstituted piperidinyl)-4-substituted piperidine derivatives |
| DE19608665A1 (de) | 1996-03-06 | 1997-09-11 | Boehringer Ingelheim Kg | Neue Arylglycinamidderivate, Verfahren zu ihrer Herstellung und diese Verbindungen enthaltende pharmazeutische Zusammensetzungen |
| US6057323A (en) | 1996-03-08 | 2000-05-02 | Adolor Corporation | Kappa agonist compounds pharmaceutical formulations and method of prevention and treatment of pruritus therewith |
| AU707139B2 (en) | 1996-04-03 | 1999-07-01 | Merck & Co., Inc. | Inhibitors of farnesyl-protein transferase |
| US5859012A (en) | 1996-04-03 | 1999-01-12 | Merck & Co., Inc. | Inhibitors of farnesyl-protein transferase |
| CA2249599A1 (en) | 1996-04-03 | 1997-10-09 | Dong D. Wei | Inhibitors of farnesyl-protein transferase |
| AU715667B2 (en) | 1996-04-03 | 2000-02-10 | Merck & Co., Inc. | Inhibitors of farnesyl-protein transferase |
| AU3359697A (en) | 1996-07-08 | 1998-02-02 | Yamanouchi Pharmaceutical Co., Ltd. | Bone resorption inhibitors |
| US6117855A (en) | 1996-10-07 | 2000-09-12 | Merck Sharp & Dohme Ltd. | Use of a NK-1 receptor antagonist and an antidepressant and/or an anti-anxiety agent |
| US5929077A (en) | 1996-11-08 | 1999-07-27 | Leftheris; Katerina | Thioproline-containing inhibitors of farnesyl protein transferase |
| US5977104A (en) | 1996-12-02 | 1999-11-02 | Merck Sharp & Dohme Ltd. | Use of NK-1 receptor antagonists for treating bipolar disorders |
| WO1998024443A1 (en) | 1996-12-02 | 1998-06-11 | Merck Sharp & Dohme Limited | Use of nk-1 receptor antagonists for treating bipolar disorders |
| US6114315A (en) | 1996-12-02 | 2000-09-05 | Merck Sharp & Dohme Ltd. | Use of NK-1 receptor antagonists for treating major depressive disorders with anxiety |
| DE19652273A1 (de) * | 1996-12-16 | 1998-06-18 | Basf Ag | Monoolefinische C¶5¶-Mononitrile, Verfahren zu ihrer Herstellung und ihre Verwendung |
| AUPO735997A0 (en) | 1997-06-17 | 1997-07-10 | Fujisawa Pharmaceutical Co., Ltd. | Piperazine derivatives |
| EP1014984A1 (de) | 1997-08-27 | 2000-07-05 | Merck & Co., Inc. | Prenyl-protein transferase inhibitoren |
| DE69824037T2 (de) | 1997-11-24 | 2005-06-02 | Merck & Co., Inc. | Beta-alanin-derivate als zell-adhäsions-inhibitoren |
| IL137517A0 (en) | 1998-01-27 | 2001-07-24 | Aventis Pharm Prod Inc | Substituted oxoazaheterocyclyl factor xa inhibitors |
| GB9923748D0 (en) | 1999-10-07 | 1999-12-08 | Glaxo Group Ltd | Chemical compounds |
| WO2002000631A2 (en) * | 2000-06-29 | 2002-01-03 | Fujisawa Pharmaceutical Co., Ltd. | Benzhydryl derivatives |
| AUPR237301A0 (en) * | 2001-01-02 | 2001-01-25 | Fujisawa Pharmaceutical Co., Ltd. | Benzhydryl derivatives |
| DE50110956D1 (de) | 2000-10-12 | 2006-10-19 | Viromics Gmbh | Proteasome inhibitoren zur behandlung von hepatitis-virus infektionen |
| GB0025354D0 (en) * | 2000-10-17 | 2000-11-29 | Glaxo Group Ltd | Chemical compounds |
| US20030022891A1 (en) | 2000-12-01 | 2003-01-30 | Anandan Palani | MCH antagonists and their use in the treatment of obesity |
| GB0203020D0 (en) * | 2002-02-08 | 2002-03-27 | Glaxo Group Ltd | Chemical compounds |
| US20040029865A1 (en) | 2002-05-23 | 2004-02-12 | Acker Brad A. | Bis-arylsulfones |
| MY141736A (en) | 2002-10-08 | 2010-06-15 | Elanco Animal Health Ireland | Substituted 1,4-di-piperidin-4-yi-piperazine derivatives and their use as neurokinin antagonists |
| GB0308968D0 (en) * | 2003-04-17 | 2003-05-28 | Glaxo Group Ltd | Medicaments |
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- 2003-02-10 AU AU2003205753A patent/AU2003205753B9/en not_active Expired
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Representative=s name: MURGITROYD & CO, MANNERHEIMINTIE 12 B |
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