NZ531503A - Prostaglandin analogs as chloride channel opener - Google Patents
Prostaglandin analogs as chloride channel openerInfo
- Publication number
- NZ531503A NZ531503A NZ531503A NZ53150302A NZ531503A NZ 531503 A NZ531503 A NZ 531503A NZ 531503 A NZ531503 A NZ 531503A NZ 53150302 A NZ53150302 A NZ 53150302A NZ 531503 A NZ531503 A NZ 531503A
- Authority
- NZ
- New Zealand
- Prior art keywords
- alkyl
- compound
- hydroxy
- halogen
- hydrogen
- Prior art date
Links
- 102000011045 Chloride Channels Human genes 0.000 title claims description 21
- 108010062745 Chloride Channels Proteins 0.000 title claims description 21
- 150000003180 prostaglandins Chemical class 0.000 title description 5
- 150000001875 compounds Chemical class 0.000 claims description 127
- 125000000217 alkyl group Chemical group 0.000 claims description 106
- -1 prostaglandin compound Chemical class 0.000 claims description 87
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 77
- 239000000203 mixture Substances 0.000 claims description 71
- 125000003545 alkoxy group Chemical group 0.000 claims description 55
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 claims description 54
- 239000001257 hydrogen Substances 0.000 claims description 47
- 229910052739 hydrogen Inorganic materials 0.000 claims description 47
- 229920006395 saturated elastomer Polymers 0.000 claims description 47
- 229910052736 halogen Inorganic materials 0.000 claims description 46
- 229940125904 compound 1 Drugs 0.000 claims description 44
- 125000003118 aryl group Chemical group 0.000 claims description 42
- 150000002367 halogens Chemical class 0.000 claims description 41
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- 125000004043 oxo group Chemical group O=* 0.000 claims description 30
- 125000000623 heterocyclic group Chemical group 0.000 claims description 29
- 108091006146 Channels Proteins 0.000 claims description 28
- 125000004104 aryloxy group Chemical group 0.000 claims description 24
- 238000012360 testing method Methods 0.000 claims description 24
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 20
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- 125000001931 aliphatic group Chemical group 0.000 claims description 17
- 125000005843 halogen group Chemical group 0.000 claims description 17
- 238000000034 method Methods 0.000 claims description 17
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- 229910052717 sulfur Chemical group 0.000 claims description 11
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 10
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Classifications
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Landscapes
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| US31591701P | 2001-08-31 | 2001-08-31 | |
| US37210402P | 2002-04-15 | 2002-04-15 | |
| PCT/JP2002/008705 WO2003030912A1 (en) | 2001-08-31 | 2002-08-29 | Prostaglandin analogs as chloride channel opener |
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| US7732487B2 (en) * | 2001-11-19 | 2010-06-08 | Sucampo Ag | Method for treating a disease or condition responsive to opening of C1C-2 channel |
| WO2004037268A1 (en) * | 2002-10-23 | 2004-05-06 | Sucampo Ag | Prostaglandin compounds for the treatment of obesity |
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| EP1641462B1 (en) * | 2003-07-03 | 2010-11-24 | Sucampo AG | Enteric coated composition comprising prostaglandin analogs as chloride channel opener |
| TWI495471B (zh) | 2003-08-12 | 2015-08-11 | R Tech Ueno Ltd | 促進毛髮生長之組成物及方法 |
| TWI387454B (zh) | 2004-09-02 | 2013-03-01 | 蘇坎波公司 | 治療胃腸道疾病之方法及組成物 |
| US8518962B2 (en) | 2005-03-07 | 2013-08-27 | The University Of Chicago | Use of opioid antagonists |
| CN104248763A (zh) * | 2005-03-07 | 2014-12-31 | 芝加哥大学 | 阿片样物质拮抗剂用于减少内皮细胞增殖和迁移的用途 |
| US9662325B2 (en) | 2005-03-07 | 2017-05-30 | The University Of Chicago | Use of opioid antagonists to attenuate endothelial cell proliferation and migration |
| US8524731B2 (en) | 2005-03-07 | 2013-09-03 | The University Of Chicago | Use of opioid antagonists to attenuate endothelial cell proliferation and migration |
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| JP5427029B2 (ja) * | 2006-09-06 | 2014-02-26 | スキャンポ・アーゲー | 消化管の重炭酸分泌を促進するための方法および組成物 |
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| CN101318948B (zh) * | 2008-04-01 | 2011-04-27 | 上海天伟生物制药有限公司 | 鲁比前列酮晶体、其制备方法及用途 |
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| SG178315A1 (en) * | 2009-08-07 | 2012-03-29 | Scipharm Sarl | Composition for the treatment of cystic fibrosis |
| MX342548B (es) * | 2009-09-18 | 2016-10-04 | Merck Sharp & Dohme Corp * | Uso del antagonista del receptor opiaceo para los trastornos del tracto gastrointestinal. |
| HUE031652T2 (en) | 2011-02-07 | 2017-07-28 | Scipharm Sarl | New composition for treating cystic fibrosis |
| US8945605B2 (en) | 2011-06-07 | 2015-02-03 | Parion Sciences, Inc. | Aerosol delivery systems, compositions and methods |
| AU2012267938B2 (en) | 2011-06-07 | 2017-05-04 | Parion Sciences, Inc. | Methods of treatment |
| US10724986B2 (en) | 2012-11-29 | 2020-07-28 | Indiana University Research & Technology Corporation | Dielectric electrolyte measurement device |
| WO2014159679A1 (en) | 2013-03-12 | 2014-10-02 | The United States Of America, As Represented By The Secretary, Department Of Health & Human Services | Methods for using lubiprostone to absorb fluid from the subretinal space |
| US20150057351A1 (en) * | 2013-08-22 | 2015-02-26 | Sucampo Ag | Method for treating neuropathic pain |
| US20160228403A1 (en) * | 2013-10-04 | 2016-08-11 | Tohoku University | Agent for preventing or ameliorating renal dysfunction |
| US11534404B2 (en) | 2016-10-06 | 2022-12-27 | Sucampo Ag | Multilayer beads for pharmaceutical use |
| US11376287B2 (en) | 2016-10-20 | 2022-07-05 | Biofermin Pharmaceutical Co., Ltd. | Agent acting on transcellular ion transporter in intestinal tract, agent for activating chloride channel, agent for preventing or treating renal disease, or agent for promoting defecation |
| US10457623B1 (en) * | 2018-07-13 | 2019-10-29 | Chirogate International Inc. | Process for the preparation of Lubiprostone and intermediates thereof |
Family Cites Families (24)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IE43462B1 (en) * | 1975-06-23 | 1981-03-11 | Pfizer | Substituted tetranorprostaglandins |
| US4091207A (en) * | 1976-04-22 | 1978-05-23 | Pfizer Inc. | Prostaglandin intermediate including oxathio heterocyclic ring |
| IT1098350B (it) * | 1977-07-28 | 1985-09-07 | Upjohn Co | Derivati prostaglandinici |
| JPS6033429B2 (ja) * | 1980-04-28 | 1985-08-02 | 小野薬品工業株式会社 | プロスタグランジン類似化合物 |
| CA1322749C (en) | 1987-01-28 | 1993-10-05 | Ryuzo Ueno | Prostaglandins of the d series, and tranquilizers and soporifics containing the same |
| US5166174A (en) | 1987-01-28 | 1992-11-24 | K.K. Ueno Seiyaku Oyo Kenkyujo | Prostaglandins E and anti-ulcers containing same |
| US5221763A (en) | 1987-04-30 | 1993-06-22 | R-Tech Ueno, Ltd. | Prostaglandins of the F series |
| DE3873007T2 (de) | 1987-10-02 | 1992-12-03 | Ueno Seiyaku Oyo Kenkyujo Kk | Kathartica. |
| JPH0681728B2 (ja) * | 1987-10-02 | 1994-10-19 | 株式会社上野製薬応用研究所 | 下 剤 |
| JP2579193B2 (ja) | 1988-07-19 | 1997-02-05 | 小野薬品工業株式会社 | １６，１６−ジフルオロ−１５−オキソ−１５−デオキシｐｇｅ誘導体 |
| JPH0791192B2 (ja) * | 1989-11-22 | 1995-10-04 | 株式会社上野製薬応用研究所 | ガス交換機能不全処置剤 |
| CA2030344C (en) | 1989-11-22 | 2000-04-18 | Ryuji Ueno | Treatment of pulmonary dysfunction with 15-keto-prostaglandin compounds |
| TW249226B (enExample) | 1990-04-04 | 1995-06-11 | Aderk Ueno Kk | |
| EP0455448B1 (en) | 1990-05-01 | 1998-12-09 | R-Tech Ueno Ltd. | Treatment of pancreatic disease with 15-keto-prostaglandin E compounds |
| CA2150287C (en) * | 1994-06-03 | 2004-08-10 | Ryuji Ueno | Agent for treating hepato-biliary diseases |
| US6015828A (en) | 1996-05-31 | 2000-01-18 | Cuppoletti; John | Chemical modification of chloride channels as a treatment for cystic fibrosis and other diseases |
| JP3187438B2 (ja) | 1996-06-10 | 2001-07-11 | 株式会社アールテック・ウエノ | エンドセリン拮抗剤 |
| US6291521B1 (en) * | 1997-10-13 | 2001-09-18 | R-Tech Ueno, Ltd. | Anti-portal hypertensive agent |
| CA2279267C (en) * | 1997-11-28 | 2010-01-12 | R-Tech Ueno, Ltd. | Use of 15-ketoprostaglandin e compounds as endothelin antagonist |
| WO1999061029A1 (en) * | 1998-05-25 | 1999-12-02 | Taisho Pharmaceutical Co., Ltd. | Sleep inducing agent |
| NZ521464A (en) | 2000-03-24 | 2004-09-24 | Sucampo Ag | Apoptosis inhibiting composition comprising a 15-keto-prostaglandin or derivative thereof |
| JP4183943B2 (ja) | 2000-04-06 | 2008-11-19 | スキャンポ・アーゲー | １５−ケトプロスタグランジンを含む胆汁分泌促進剤組成物 |
| TWI302100B (en) | 2001-05-02 | 2008-10-21 | Sucampo Ag | Composition for treating drug-induced constipation |
| FR2829293B1 (fr) * | 2001-08-31 | 2003-11-14 | Centre Nat Rech Scient | Memoire moleculaire et son procede de fabrication |
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2002
- 2002-08-29 EP EP02767866.3A patent/EP1420794B1/en not_active Expired - Lifetime
- 2002-08-29 NZ NZ531503A patent/NZ531503A/en not_active IP Right Cessation
- 2002-08-29 JP JP2003533944A patent/JP4786866B2/ja not_active Expired - Lifetime
- 2002-08-29 CA CA2458471A patent/CA2458471C/en not_active Expired - Lifetime
- 2002-08-29 AU AU2002330747A patent/AU2002330747B2/en not_active Expired
- 2002-08-29 WO PCT/JP2002/008705 patent/WO2003030912A1/en not_active Ceased
- 2002-08-29 MX MXPA04002006A patent/MXPA04002006A/es active IP Right Grant
- 2002-08-29 BR BR0212233-2A patent/BR0212233A/pt not_active Application Discontinuation
- 2002-08-30 AR ARP020103284A patent/AR036391A1/es active IP Right Grant
- 2002-08-30 US US10/231,341 patent/US7064148B2/en not_active Expired - Lifetime
- 2002-08-30 TW TW091119830A patent/TWI298256B/zh not_active IP Right Cessation
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2006
- 2006-01-18 US US11/333,511 patent/US7253295B2/en not_active Expired - Lifetime
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- 2011-01-07 JP JP2011001763A patent/JP5568021B2/ja not_active Expired - Lifetime
Also Published As
| Publication number | Publication date |
|---|---|
| JP5568021B2 (ja) | 2014-08-06 |
| US20030130352A1 (en) | 2003-07-10 |
| CA2458471C (en) | 2012-07-31 |
| CA2458471A1 (en) | 2003-04-17 |
| EP1420794A1 (en) | 2004-05-26 |
| WO2003030912A1 (en) | 2003-04-17 |
| TWI298256B (en) | 2008-07-01 |
| JP2005504836A (ja) | 2005-02-17 |
| JP4786866B2 (ja) | 2011-10-05 |
| JP2011102313A (ja) | 2011-05-26 |
| EP1420794B1 (en) | 2017-12-27 |
| AR036391A1 (es) | 2004-09-08 |
| US20060122411A1 (en) | 2006-06-08 |
| AU2002330747B2 (en) | 2007-07-19 |
| MXPA04002006A (es) | 2004-06-07 |
| US7064148B2 (en) | 2006-06-20 |
| BR0212233A (pt) | 2004-10-05 |
| US7253295B2 (en) | 2007-08-07 |
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