ES2204458T3 - Agonista selectivos del receptor ep4 en el tratamiento de la osteoporisis. - Google Patents
Agonista selectivos del receptor ep4 en el tratamiento de la osteoporisis.Info
- Publication number
- ES2204458T3 ES2204458T3 ES00311034T ES00311034T ES2204458T3 ES 2204458 T3 ES2204458 T3 ES 2204458T3 ES 00311034 T ES00311034 T ES 00311034T ES 00311034 T ES00311034 T ES 00311034T ES 2204458 T3 ES2204458 T3 ES 2204458T3
- Authority
- ES
- Spain
- Prior art keywords
- phenyl
- pyrrolidin
- butyl
- hydroxy
- oxo
- 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.)
- Expired - Lifetime
Links
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- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/4015—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil having oxo groups directly attached to the heterocyclic ring, e.g. piracetam, ethosuximide
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/18—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member
- C07D207/22—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D207/24—Oxygen or sulfur atoms
- C07D207/26—2-Pyrrolidones
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- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
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- A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/18—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member
- C07D207/20—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/10—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a carbon chain containing aromatic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Physical Education & Sports Medicine (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
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- Life Sciences & Earth Sciences (AREA)
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- Engineering & Computer Science (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Rheumatology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Plural Heterocyclic Compounds (AREA)
- Pyrrole Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US17135399P | 1999-12-22 | 1999-12-22 | |
| US171353P | 1999-12-22 |
Publications (1)
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|---|---|
| ES2204458T3 true ES2204458T3 (es) | 2004-05-01 |
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| ES00311034T Expired - Lifetime ES2204458T3 (es) | 1999-12-22 | 2000-12-11 | Agonista selectivos del receptor ep4 en el tratamiento de la osteoporisis. |
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| US20010056060A1 (en) * | 2000-02-07 | 2001-12-27 | Cameron Kimberly O. | Treatment of osteoporsis with EP2/EP4 receptor selective agonists |
| CN1476429A (zh) * | 2000-11-27 | 2004-02-18 | �Ʒ� | 治疗骨质疏松的ep4受体选择性激动剂 |
| EP1408961B1 (en) | 2001-07-16 | 2007-07-11 | F. Hoffmann-La Roche Ag | 2 pyrrolidone derivatives as prostanoid agonists |
| EP1409455B1 (en) * | 2001-07-16 | 2006-01-04 | F. Hoffmann-La Roche Ag | Prostaglandin analogues-as ep4 receptor agonists |
| CN1893977B (zh) * | 2001-07-23 | 2012-12-05 | 小野药品工业株式会社 | 以ep4激动剂为活性成分的治疗与骨质损失有关的疾病的药物 |
| JP4273407B2 (ja) * | 2001-07-23 | 2009-06-03 | 小野薬品工業株式会社 | Ｅｐ４アゴニストを有効成分とする骨量低下疾患の治療剤 |
| JPWO2003041717A1 (ja) * | 2001-11-12 | 2005-03-03 | 小野薬品工業株式会社 | プロスタグランジン誘導体を有効成分とする局所投与用持続性フィルム状製剤 |
| US20040254230A1 (en) * | 2001-12-03 | 2004-12-16 | Ogidigben Miller J. | Method for treating ocular hypertension |
| WO2003047417A2 (en) * | 2001-12-03 | 2003-06-12 | Merck & Co., Inc. | Ep4 receptor agonist, compositions and methods thereof |
| US7335680B2 (en) | 2001-12-20 | 2008-02-26 | Laboratoires Serono Sa | Pyrrolidine derivatives as prostaglandin modulators |
| TW200305425A (en) | 2002-03-05 | 2003-11-01 | Ono Pharmaceutical Co | 8-Azaprostaglandin derivatives and medicament containing same as active ingredient |
| JP2005526080A (ja) * | 2002-03-18 | 2005-09-02 | ファイザー・プロダクツ・インク | 肝不全、動脈管閉鎖、緑内障又は高眼圧の治療のための選択的ｅｐ４受容体アゴニストの使用 |
| US6573294B1 (en) * | 2002-05-14 | 2003-06-03 | Allergan, Inc. | 8-azaprostaglandin analogs as agents for lowering intraocular pressure |
| AU2011202937B2 (en) * | 2002-05-14 | 2012-06-07 | Allergan, Inc. | 8-azaprostaglandin analogs as agents for lowering intraocular pressure |
| ATE487514T1 (de) | 2002-06-06 | 2010-11-15 | Merck Frosst Canada Ltd | 1,5-disubstituierte pyrrolid-2-on-derivate zur verwendung als ep4 rezeptor agonisten zur behandlung von augenkrankheiten wie z.b. glaukom |
| US7419999B2 (en) | 2002-06-10 | 2008-09-02 | Applied Research Systems Ars Holding N.V. | Gamma lactams as prostaglandin agonists and use thereof |
| AU2003272963A1 (en) | 2002-10-10 | 2004-05-04 | Ono Pharmaceutical Co., Ltd. | Endogenous repair factor production promoters |
| AU2003287481B2 (en) | 2002-11-08 | 2009-04-23 | Merck & Co., Inc. | Ophthalmic compositions for treating ocular hypertension |
| US7196082B2 (en) | 2002-11-08 | 2007-03-27 | Merck & Co. Inc. | Ophthalmic compositions for treating ocular hypertension |
| US7053085B2 (en) | 2003-03-26 | 2006-05-30 | Merck & Co. Inc. | EP4 receptor agonist, compositions and methods thereof |
| CN1735597A (zh) | 2003-01-10 | 2006-02-15 | 霍夫曼-拉罗奇有限公司 | 作为前列腺素激动剂的2－哌啶酮衍生物 |
| JP4582456B2 (ja) * | 2003-01-21 | 2010-11-17 | 小野薬品工業株式会社 | ８−アザプロスタグランジン誘導体およびその医薬用途 |
| US7276531B2 (en) | 2003-03-03 | 2007-10-02 | Applied Research Systems Ars Holding N.V. | G-lactam derivatives as prostaglandin agonists |
| US6734206B1 (en) | 2003-06-02 | 2004-05-11 | Allergan, Inc. | 3-oxa-8-azaprostaglandin analogs as agents for lowering intraocular pressure |
| US6734201B1 (en) * | 2003-06-02 | 2004-05-11 | Allergan, Inc. | 8-Azaprostaglandin carbonate and thiocarbonate analogs as therapeutic agents |
| US7179820B2 (en) | 2003-06-06 | 2007-02-20 | Allergan, Inc. | Piperidinyl prostaglandin E analogs |
| EP1654219A2 (en) * | 2003-07-18 | 2006-05-10 | Applied Research Systems ARS Holding N.V. | Hydrazide derivatives as prostaglandin receptors modulators |
| CN1845914A (zh) | 2003-09-02 | 2006-10-11 | 默克公司 | 用于治疗眼压过高的眼用组合物 |
| JP2007504236A (ja) | 2003-09-04 | 2007-03-01 | メルク エンド カムパニー インコーポレーテッド | 高眼圧症を治療するための眼用組成物 |
| NZ545401A (en) | 2003-09-04 | 2008-10-31 | Merck & Co Inc | Ophthalmic compositions for treating ocular hypertension |
| WO2005027931A1 (en) * | 2003-09-19 | 2005-03-31 | Pfizer Products Inc. | Pharmaceutical compositions and methods comprising combinations of 2-alkylidene-19-nor-vitamin d derivatives and an ep2 or ep4 selective agonist |
| WO2005080367A1 (en) | 2004-02-12 | 2005-09-01 | Pharmagene Laboratories Limited | Ep2 receptor agonists |
| US7563816B2 (en) | 2004-07-20 | 2009-07-21 | Merck & Co. Inc. | Ophthalmic compositions for treating ocular hypertension |
| CA2587318A1 (en) | 2004-12-06 | 2006-06-15 | Laboratoires Serono S.A. | Pyrrolidin-2-one derivatives for use as dp1 receptor agonists |
| US7531533B2 (en) | 2005-01-27 | 2009-05-12 | Asahi Kasei Pharma Corporation | 6-Membered heterocyclic compound and use thereof |
| US20090074844A1 (en) | 2005-04-28 | 2009-03-19 | Ono Pharmaceutical Co., Ltd. | Trenadermal absorption preparation |
| KR100686186B1 (ko) * | 2005-06-13 | 2007-02-26 | 영진종합건설 주식회사 | 교량용 배수 구조물 |
| JP2009505973A (ja) | 2005-08-09 | 2009-02-12 | アステランド ユーケイ リミテッド | Ｅｐ２受容体アゴニスト |
| KR20090075864A (ko) | 2006-10-26 | 2009-07-09 | 오노 야꾸힝 고교 가부시키가이샤 | 첨부제 |
| WO2008073748A1 (en) | 2006-12-08 | 2008-06-19 | University Of Rochester | Expansion of hematopoietic stem cells |
| US8063240B2 (en) | 2007-11-14 | 2011-11-22 | Cayman Chemical Company, Incorporated | Prostaglandin E1 and E2 analogs for the treatment of various medical conditions |
| CA2738045C (en) | 2010-05-28 | 2019-02-19 | Simon Fraser University | Conjugate compounds, methods of making same, and uses thereof |
| CA2842906A1 (en) | 2011-08-02 | 2013-02-07 | Ono Pharmaceutical Co., Ltd. | Left ventricular diastolic function improving agent |
| EP3175852B1 (en) | 2012-07-19 | 2019-03-06 | Cayman Chemical Company, Incorporated | Difluorolactam compositions for ep4-mediated osteo related diseases and conditions |
| US20150272874A1 (en) | 2012-10-29 | 2015-10-01 | Cardio Incorporated | Pulmonary disease-specific therapeutic agent |
| US9676712B2 (en) | 2013-03-15 | 2017-06-13 | Cayman Chemical Company, Inc. | Lactam compounds as EP4 receptor-selective agonists for use in the treatment of EP4-mediated diseases and conditions |
| EA201591793A1 (ru) * | 2013-03-15 | 2016-01-29 | Кайман Кемикал Компани, Инк. | Лактамные соединения в качестве селективных агонистов ep4-рецепторов для применения при лечении опосредованных ep4 заболеваний и состояний |
| KR20160048054A (ko) | 2013-07-19 | 2016-05-03 | 카이맨 케미칼 컴파니 인코포레이티드 | 골 성장의 촉진을 위한 방법, 시스템 및 조성물 |
| JP6694385B2 (ja) | 2013-08-09 | 2020-05-13 | アーデリクス，インコーポレーテッド | リン酸塩輸送阻害のための化合物及び方法 |
| JP6449166B2 (ja) | 2013-10-15 | 2019-01-09 | 小野薬品工業株式会社 | 薬剤溶出性ステントグラフト |
| JP7174982B2 (ja) | 2015-06-12 | 2022-11-18 | サイモン フレイザー ユニヴァーシティー | アミド連結ｅｐ４アゴニスト－ビスホスホネート化合物およびその使用 |
| EP3972599B1 (en) | 2019-05-21 | 2025-10-22 | Ardelyx, Inc. | Combination for lowering serum phosphate in a patient |
Family Cites Families (25)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR897566A (fr) | 1942-08-28 | 1945-03-26 | Bopp & Reuther Gmbh | Machine à rotors |
| US3528961A (en) | 1966-08-16 | 1970-09-15 | Allied Chem | Monoazo dyes from e-caprolactam |
| US3780095A (en) | 1970-04-08 | 1973-12-18 | Byk Gulden Lomberg Chem Fab | Acylated anilino-carboxylic acids and their salts |
| US3987091A (en) | 1973-04-12 | 1976-10-19 | Merck & Co., Inc. | 11,12-secoprostaglandins |
| US4033996A (en) | 1973-04-25 | 1977-07-05 | Merck & Co., Inc. | 8-Aza-9-oxo(and dioxo)-thia-11,12-secoprostaglandins |
| SE7414770L (cg-RX-API-DMAC7.html) | 1973-12-13 | 1975-06-16 | Merck & Co Inc | |
| DK366475A (da) | 1974-08-30 | 1976-03-01 | Merck & Co Inc | Fremgangsmade til fremstilling af aryloxy- eller arylthioholdige secoprostaglandiner |
| US3991106A (en) | 1974-09-13 | 1976-11-09 | Merck & Co., Inc. | 16-Ethers of 8-aza-9-dioxothia-11,12-seco-prostaglandins |
| US4055596A (en) | 1974-09-13 | 1977-10-25 | Merck & Co., Inc. | 11,12-Seco-prostaglandins |
| US4113873A (en) | 1975-04-26 | 1978-09-12 | Tanabe Seiyaku Co. Ltd. | 8-azaprostanoic acid derivatives |
| DE2528664A1 (de) * | 1975-06-27 | 1977-01-13 | Hoechst Ag | Pyrrolidone und verfahren zu ihrer herstellung |
| IL49325A (en) | 1976-03-31 | 1979-11-30 | Labaz | 8-aza-11-deoxy-pge1 derivatives,their preparation and pharmaceutical compositions containing them |
| DE2619638A1 (de) | 1976-05-04 | 1977-11-17 | Hoechst Ag | Pyrrolidone und verfahren zu ihrer herstellung |
| US4177346A (en) | 1976-08-06 | 1979-12-04 | Pfizer Inc. | 1,5-Disubstituted-2-pyrrolidones |
| US4175203A (en) | 1976-12-17 | 1979-11-20 | Merck & Co., Inc. | Interphenylene 11,12-secoprostaglandins |
| US4243678A (en) | 1977-12-30 | 1981-01-06 | Byk Gulden Lomberg Chemische Fabrik Gmbh | Acylhydrocarbylaminoalkanoic acids, compositions and uses |
| DE3000377A1 (de) | 1980-01-07 | 1981-07-09 | Boehringer Mannheim Gmbh, 6800 Mannheim | Neue sulfonamide, verfahren zu deren herstellung sowie diese verbindungen enthaltende arzneimittel |
| DE3042482A1 (de) | 1980-11-11 | 1982-06-24 | A. Nattermann & Cie GmbH, 5000 Köln | N-benzoyl- (omega) -anilinoalkancarbonsaeuren, -salze und -ester, verfahren zu ihrer herstellung und diese enthaltende pharmazeutische praeparate |
| EP0068968B1 (fr) | 1981-06-16 | 1985-09-18 | Choay S.A. | Nouveaux médicaments contenant à titre de substance active des composés du type arylbenzènesulfonamide et leurs procédés de préparation |
| AU6427596A (en) * | 1992-04-14 | 1996-10-31 | Alfred Maximillian Stessl | A boat hull |
| TW383306B (en) | 1992-12-22 | 2000-03-01 | Lilly Co Eli | New use of 2-phenyl-3-aroylbenzothiophenes in lowering serum cholesterol |
| ATE390917T1 (de) * | 1996-12-20 | 2008-04-15 | Pfizer | Prävention und behandlung von skeletterkrankungen mit ep2 subtyp selektiven prostaglandin e2 agonisten |
| GB2330307A (en) * | 1998-02-07 | 1999-04-21 | Glaxo Group Ltd | EP4 Receptor antagonists as bone resorption inhibitors |
| AU1444200A (en) * | 1998-10-15 | 2000-05-01 | Merck & Co., Inc. | Methods for inhibiting bone resorption |
| AU6427599A (en) * | 1998-10-15 | 2000-05-01 | Merck & Co., Inc. | Methods for stimulating bone formation |
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