JP2010521516A - 疼痛および過敏性腸症候群の治療におけるキノリン誘導体の使用 - Google Patents
疼痛および過敏性腸症候群の治療におけるキノリン誘導体の使用 Download PDFInfo
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- JP2010521516A JP2010521516A JP2009554019A JP2009554019A JP2010521516A JP 2010521516 A JP2010521516 A JP 2010521516A JP 2009554019 A JP2009554019 A JP 2009554019A JP 2009554019 A JP2009554019 A JP 2009554019A JP 2010521516 A JP2010521516 A JP 2010521516A
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Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
-
- 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
- A61P25/04—Centrally acting analgesics, e.g. opioids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
Landscapes
- Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Chemistry (AREA)
- Epidemiology (AREA)
- Pain & Pain Management (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Rheumatology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Biomedical Technology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Quinoline Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB0705424A GB0705424D0 (en) | 2007-03-21 | 2007-03-21 | Use of compounds in the treatment of pain and irritable bowel syndrome |
| GB0712390A GB0712390D0 (en) | 2007-06-26 | 2007-06-26 | Use of compounds in the treatment of pain and irritable bowel syndrome |
| PCT/EP2008/053285 WO2008113818A1 (en) | 2007-03-21 | 2008-03-19 | Use of quinoline derivatives in the treatment of pain and irritable bowel syndrome |
Publications (2)
| Publication Number | Publication Date |
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| JP2010521516A true JP2010521516A (ja) | 2010-06-24 |
| JP2010521516A5 JP2010521516A5 (enExample) | 2011-04-28 |
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| EP (1) | EP2120950B1 (enExample) |
| JP (1) | JP2010521516A (enExample) |
| ES (1) | ES2389958T3 (enExample) |
| WO (1) | WO2008113818A1 (enExample) |
Families Citing this family (11)
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| JP4198733B2 (ja) | 2003-07-22 | 2008-12-17 | アリーナ ファーマシューティカルズ， インコーポレイテッド | 関連性障害の予防および処置に有用な、５−ｈｔ２ａセロトニンレセプターのモジュレーターとしてのジアリールおよびアリールへテロアリールウレア誘導体 |
| KR20090128426A (ko) | 2007-03-23 | 2009-12-15 | 애보트 게엠베하 운트 콤파니 카게 | 세로토닌 ５―ｈｔ６ 수용체의 조절에 반응하는 장애를 치료하는 데 적합한 퀴놀린 화합물 |
| EP2508177A1 (en) | 2007-12-12 | 2012-10-10 | Glaxo Group Limited | Combinations comprising 3-phenylsulfonyl-8-piperazinyl-1yl-quinoline |
| US20110021538A1 (en) | 2008-04-02 | 2011-01-27 | Arena Pharmaceuticals, Inc. | Processes for the preparation of pyrazole derivatives useful as modulators of the 5-ht2a serotonin receptor |
| US9126946B2 (en) | 2008-10-28 | 2015-09-08 | Arena Pharmaceuticals, Inc. | Processes useful for the preparation of 1-[3-(4-bromo-2-methyl-2H-pyrazol-3-yl)-4-methoxy-phenyl]-3-(2,4-difluoro-phenyl)urea and crystalline forms related thereto |
| AU2012321345B2 (en) | 2011-10-03 | 2016-03-17 | The University Of Utah Research Foundation | Application of 5-HT6 receptor antagonists for the alleviation of cognitive deficits of down syndrome |
| AU2013229854B2 (en) * | 2012-03-08 | 2017-08-17 | Spr Therapeutics, Inc. | System and method for treatment of pain related to limb joint replacement surgery |
| US20160038484A1 (en) * | 2013-04-03 | 2016-02-11 | The University Of Utah Research Foundation | Application of 5-ht6 receptor antagonists for the alleviation of cognitive deficits of down syndrome |
| WO2016201373A1 (en) | 2015-06-12 | 2016-12-15 | Axovant Sciences Ltd. | Diaryl and arylheteroaryl urea derivatives useful for the prophylaxis and treatment of rem sleep behavior disorder |
| HK1247555A1 (zh) | 2015-07-15 | 2018-09-28 | Axovant Sciences Gmbh | 用於预防和治疗与神经变性疾病相关的幻觉的作为5-ht2a血清素受体的调节剂的二芳基脲和芳基杂芳基脲衍生物 |
| WO2017134280A1 (en) * | 2016-02-05 | 2017-08-10 | Pharnext | Novel combinatorial therapies of neurological disorders |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2005528587A (ja) * | 2002-02-01 | 2005-09-22 | バイエル・ヘルスケア・アクチェンゲゼルシャフト | 新規ヒト５−ｈｔ６受容体に関連する疾患のための診断用および治療用物質 |
| JP2005531518A (ja) * | 2002-03-27 | 2005-10-20 | グラクソ グループ リミテッド | キノリン誘導体および５−ｈｔ６リガンドとしてのその使用 |
Family Cites Families (35)
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|---|---|---|---|---|
| US5596001A (en) * | 1993-10-25 | 1997-01-21 | Pfizer Inc. | 4-aryl-3-(heteroarylureido)quinoline derivatves |
| US5576338A (en) * | 1995-02-15 | 1996-11-19 | Merck Frosst Canada, Inc. | Bis (biaryl) compounds as inhibitors of leukotriene biosynthesis |
| US20010051719A1 (en) * | 1996-12-19 | 2001-12-13 | Smithkline Beecham P.L.C. | Novel compounds |
| US6207679B1 (en) * | 1997-06-19 | 2001-03-27 | Sepracor, Inc. | Antimicrobial agents uses and compositions related thereto |
| HUP0003364A3 (en) * | 1997-06-19 | 2002-03-28 | Sepracor Inc Marlborough | Quinoline-indole antimicrobial agents, uses and compositions related thereto |
| US6376670B1 (en) * | 1997-06-19 | 2002-04-23 | Sepracor Inc. | Quinoline-indole antimicrobial agents, uses and compositions related thereto |
| EP0994862B1 (en) * | 1997-07-11 | 2005-06-01 | SmithKline Beecham plc | Sulphonamide derivatives being 5-ht6 receptor antagonists and process for their preparation |
| GB9801392D0 (en) * | 1998-01-22 | 1998-03-18 | Smithkline Beecham Plc | Novel compounds |
| GB9818916D0 (en) * | 1998-08-28 | 1998-10-21 | Smithkline Beecham Plc | Use |
| GB9820113D0 (en) * | 1998-09-15 | 1998-11-11 | Merck Sharp & Dohme | Therapeutic agents |
| US6403808B1 (en) * | 1999-12-10 | 2002-06-11 | Virginia Commonwealth University | Selective 5-HT6 receptor ligands |
| US6310212B1 (en) * | 2000-03-28 | 2001-10-30 | Neurogen Corporation | 4-substituted quinoline derivatives |
| GB0021450D0 (en) * | 2000-08-31 | 2000-10-18 | Smithkline Beecham Plc | Novel compounds |
| IL154685A0 (en) * | 2000-10-20 | 2003-09-17 | Biovitrum Ab | 2-,3-,4-, or 5-substituted-n1-(benzensulfonyl) indoles and their use in therapy |
| DE10053813A1 (de) * | 2000-10-30 | 2002-05-08 | Bayer Ag | Neue Verwendung von Sulfonamiden |
| WO2002042293A1 (en) * | 2000-11-21 | 2002-05-30 | Smithkline Beecham P.L.C. | Isoquinoline derivatives useful in the treatment of cns disorders |
| WO2002041889A2 (en) * | 2000-11-24 | 2002-05-30 | Smithkline Beecham P.L.C. | Indolsulfonyl compounds useful in the treatment of cns disorders |
| JP4187642B2 (ja) * | 2001-06-07 | 2008-11-26 | エフ．ホフマン−ラ ロシュ アーゲー | ５−ｈｔ６受容体親和性を有する新規インドール誘導体 |
| ITRM20010356A1 (it) * | 2001-06-21 | 2002-12-23 | Sigma Tau Ind Farmaceuti | "5-alogeno derivati della triptamina utili come ligandi del recettore5-ht6 e/o 5-ht7 della serotonina. |
| WO2003062205A1 (en) * | 2001-12-21 | 2003-07-31 | Smithkline Beecham P.L.C. | 7-sulfonyl-3-benzazepine derivatives as modulators of the dopamine receptor and their use for the treatment of cns disorders |
| GB0202679D0 (en) * | 2002-02-05 | 2002-03-20 | Glaxo Group Ltd | Novel compounds |
| ES2260607T3 (es) * | 2002-02-13 | 2006-11-01 | Glaxo Group Limited | Derivados de 7-arilsulfonamido-2,3,4,5-tetrahidro-1h-benzo-diazepina con afinidad por los receptores 5-ht6 para el tratamiento de trastornos del snc. |
| US7943639B2 (en) * | 2002-06-20 | 2011-05-17 | Proximagen Limited | Compounds |
| RU2350602C2 (ru) * | 2002-12-03 | 2009-03-27 | Ф.Хоффманн-Ля Рош Аг | Аминоалкоксииндолы, как лиганды рецептора 5-нт6, для лечения заболеваний цнс |
| CN100482662C (zh) * | 2003-02-14 | 2009-04-29 | 惠氏公司 | 作为5-羟基色胺-6配体的杂环基-3-磺酰基氮杂吲哚或-氮杂吲唑衍生物 |
| GB0305575D0 (en) * | 2003-03-11 | 2003-04-16 | Glaxo Group Ltd | Novel compounds |
| GB0321473D0 (en) * | 2003-09-12 | 2003-10-15 | Glaxo Group Ltd | Novel compounds |
| GB0322510D0 (en) * | 2003-09-25 | 2003-10-29 | Glaxo Group Ltd | Novel compounds |
| GB0322629D0 (en) * | 2003-09-26 | 2003-10-29 | Glaxo Group Ltd | Novel compound |
| SE0302760D0 (sv) * | 2003-10-20 | 2003-10-20 | Biovitrum Ab | New compounds |
| WO2005066157A1 (en) * | 2004-01-02 | 2005-07-21 | Suven Life Sciences | 3-(pyrolidin-3-l) indoles as 5-ht6 receptor modulators |
| GB0407025D0 (en) * | 2004-03-29 | 2004-04-28 | Glaxo Group Ltd | Novel compounds |
| GB0411421D0 (en) * | 2004-05-21 | 2004-06-23 | Glaxo Group Ltd | Novel compounds |
| EP1753764B1 (en) * | 2004-06-09 | 2008-10-29 | Glaxo Group Limited | Pyrrolopyridine derivatives |
| GB0425548D0 (en) * | 2004-11-19 | 2004-12-22 | Glaxo Group Ltd | Radiolabelled ligands |
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- 2008-03-19 ES ES08718011T patent/ES2389958T3/es active Active
- 2008-03-19 JP JP2009554019A patent/JP2010521516A/ja not_active Ceased
- 2008-03-19 US US12/531,896 patent/US20100041672A1/en not_active Abandoned
- 2008-03-19 EP EP08718011A patent/EP2120950B1/en not_active Not-in-force
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2005528587A (ja) * | 2002-02-01 | 2005-09-22 | バイエル・ヘルスケア・アクチェンゲゼルシャフト | 新規ヒト５−ｈｔ６受容体に関連する疾患のための診断用および治療用物質 |
| JP2005531518A (ja) * | 2002-03-27 | 2005-10-20 | グラクソ グループ リミテッド | キノリン誘導体および５−ｈｔ６リガンドとしてのその使用 |
Also Published As
| Publication number | Publication date |
|---|---|
| US20100041672A1 (en) | 2010-02-18 |
| WO2008113818A1 (en) | 2008-09-25 |
| EP2120950B1 (en) | 2012-07-04 |
| ES2389958T3 (es) | 2012-11-05 |
| EP2120950A1 (en) | 2009-11-25 |
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