ES2635635T3 - Compuestos de difluorolactama como agonistas selectivos del receptor EP4 para su uso en el tratamiento de enfermedades y afecciones mediadas por EP4 - Google Patents
Compuestos de difluorolactama como agonistas selectivos del receptor EP4 para su uso en el tratamiento de enfermedades y afecciones mediadas por EP4 Download PDFInfo
- Publication number
- ES2635635T3 ES2635635T3 ES14729106.6T ES14729106T ES2635635T3 ES 2635635 T3 ES2635635 T3 ES 2635635T3 ES 14729106 T ES14729106 T ES 14729106T ES 2635635 T3 ES2635635 T3 ES 2635635T3
- Authority
- ES
- Spain
- Prior art keywords
- oxopyrrolidin
- hydroxy
- methyl
- acid
- thiophene
- 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.)
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- 150000001875 compounds Chemical class 0.000 title claims abstract description 264
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- 239000000556 agonist Substances 0.000 title description 17
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 title description 17
- 101001117509 Homo sapiens Prostaglandin E2 receptor EP4 subtype Proteins 0.000 title description 16
- 102100024450 Prostaglandin E2 receptor EP4 subtype Human genes 0.000 title description 15
- 201000010099 disease Diseases 0.000 title description 12
- 230000001404 mediated effect Effects 0.000 title description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract description 77
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims abstract description 71
- 125000001188 haloalkyl group Chemical group 0.000 claims abstract description 38
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- 125000001424 substituent group Chemical group 0.000 claims abstract description 35
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- 229910052736 halogen Inorganic materials 0.000 claims abstract description 26
- 150000002367 halogens Chemical class 0.000 claims abstract description 26
- 125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 23
- 125000006677 (C1-C3) haloalkoxy group Chemical group 0.000 claims abstract description 22
- 125000006274 (C1-C3)alkoxy group Chemical group 0.000 claims abstract description 18
- 125000000262 haloalkenyl group Chemical group 0.000 claims abstract description 18
- 125000000008 (C1-C10) alkyl group Chemical group 0.000 claims abstract description 16
- 125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 15
- 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 15
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- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims abstract description 4
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- FAHUKNBUIVOJJR-UHFFFAOYSA-N 1-(4-fluorophenyl)-1,2,3,4-tetrahydropyrrolo[1,2-a]pyrazine Chemical compound C1=CC(F)=CC=C1C1C2=CC=CN2CCN1 FAHUKNBUIVOJJR-UHFFFAOYSA-N 0.000 claims description 88
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 88
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- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 claims description 11
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- ARLQDYZAXIPMJQ-UHFFFAOYSA-N methyl hept-5-enoate Chemical compound COC(=O)CCCC=CC ARLQDYZAXIPMJQ-UHFFFAOYSA-N 0.000 claims description 8
- HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical compound O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 claims description 8
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- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 6
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical compound CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 claims description 5
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 5
- TVQGDYNRXLTQAP-UHFFFAOYSA-N ethyl heptanoate Chemical compound CCCCCCC(=O)OCC TVQGDYNRXLTQAP-UHFFFAOYSA-N 0.000 claims description 4
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 3
- QYDYPVFESGNLHU-UHFFFAOYSA-N elaidic acid methyl ester Natural products CCCCCCCCC=CCCCCCCCC(=O)OC QYDYPVFESGNLHU-UHFFFAOYSA-N 0.000 claims description 2
- AEDIXYWIVPYNBI-UHFFFAOYSA-N heptanamide Chemical compound CCCCCCC(N)=O AEDIXYWIVPYNBI-UHFFFAOYSA-N 0.000 claims description 2
- QYDYPVFESGNLHU-KHPPLWFESA-N methyl oleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OC QYDYPVFESGNLHU-KHPPLWFESA-N 0.000 claims description 2
- 229940073769 methyl oleate Drugs 0.000 claims description 2
- RMQUEHVMCJEEOS-UHFFFAOYSA-N propan-2-yl heptanoate Chemical compound CCCCCCC(=O)OC(C)C RMQUEHVMCJEEOS-UHFFFAOYSA-N 0.000 claims description 2
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- QEMXHQIAXOOASZ-UHFFFAOYSA-N tetramethylammonium Chemical compound C[N+](C)(C)C QEMXHQIAXOOASZ-UHFFFAOYSA-N 0.000 description 1
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- 125000001889 triflyl group Chemical group FC(F)(F)S(*)(=O)=O 0.000 description 1
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Classifications
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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
- C07D207/04—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 no double bonds between ring members or between ring members and non-ring members
- C07D207/10—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 no double bonds between ring members or between ring members and non-ring members 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
- C07D207/12—Oxygen or sulfur atoms
-
- 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
- A61P1/02—Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/14—Drugs for dermatological disorders for baldness or alopecia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
- A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
-
- 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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
- A61P27/06—Antiglaucoma agents or miotics
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
-
- 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
- C07D207/22—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
-
- 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
- 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
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Physical Education & Sports Medicine (AREA)
- Rheumatology (AREA)
- Immunology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Ophthalmology & Optometry (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Biomedical Technology (AREA)
- Pain & Pain Management (AREA)
- Transplantation (AREA)
- Dermatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Pyrrole Compounds (AREA)
- Epidemiology (AREA)
- Cosmetics (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201361793736P | 2013-03-15 | 2013-03-15 | |
| US201361793736P | 2013-03-15 | ||
| PCT/US2014/029057 WO2014144584A2 (en) | 2013-03-15 | 2014-03-14 | Lactam compounds as ep4 receptor-selective agonists for use in the treatment of ep4-mediated diseases and conditions |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2635635T3 true ES2635635T3 (es) | 2017-10-04 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
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| ES14729106.6T Active ES2635635T3 (es) | 2013-03-15 | 2014-03-14 | Compuestos de difluorolactama como agonistas selectivos del receptor EP4 para su uso en el tratamiento de enfermedades y afecciones mediadas por EP4 |
Country Status (16)
| Country | Link |
|---|---|
| US (1) | US9688627B2 (https=) |
| EP (2) | EP3235817B1 (https=) |
| JP (2) | JP6317807B2 (https=) |
| KR (1) | KR20150130326A (https=) |
| CN (1) | CN105143217A (https=) |
| AU (1) | AU2014228973B2 (https=) |
| BR (1) | BR112015023080A2 (https=) |
| CA (1) | CA2906134A1 (https=) |
| DK (1) | DK2989098T3 (https=) |
| EA (1) | EA201591793A1 (https=) |
| ES (1) | ES2635635T3 (https=) |
| IL (2) | IL240988A (https=) |
| PH (1) | PH12015502165A1 (https=) |
| PT (1) | PT2989098T (https=) |
| SG (1) | SG11201507470WA (https=) |
| WO (1) | WO2014144584A2 (https=) |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2014015247A1 (en) | 2012-07-19 | 2014-01-23 | Cayman Chemical Company, Inc. | Difluorolactam compounds as ep4 receptor-selective agonists for use in the treatment of ep4-mediated disease and conditions |
| KR20160048054A (ko) | 2013-07-19 | 2016-05-03 | 카이맨 케미칼 컴파니 인코포레이티드 | 골 성장의 촉진을 위한 방법, 시스템 및 조성물 |
| CN107365329B (zh) * | 2016-05-12 | 2019-02-01 | 华东师范大学 | 一种3-甲基-2-氧代-5-庚炔基磷酸二甲酯的制备方法 |
| PT3733665T (pt) * | 2017-12-25 | 2022-10-21 | Asahi Kasei Pharma Corp | Compostos contendo unidade de 2-oxo-1,3,4-tiadiazinan-3-ilo com atividade agonista do recetor ep4 |
| AU2020256166A1 (en) | 2019-04-02 | 2021-10-14 | Aligos Therapeutics, Inc. | Compounds targeting PRMT5 |
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| US3975399A (en) | 1974-08-06 | 1976-08-17 | E. I. Du Pont De Nemours And Company | 1,5-Disubstituted-2-pyrrolidinones, -3-pyrrolin-2-ones, and -4-pyrrolin-2-ones |
| DE2517771A1 (de) | 1975-04-18 | 1976-10-28 | Schering Ag | Neue prostaglandin-acetylen-analoga und verfahren zu ihrer herstellung |
| CA1085859A (en) | 1975-06-27 | 1980-09-16 | Wilhelm Bartmann | Pyrrolidones and process for their manufacture |
| DE2528664A1 (de) | 1975-06-27 | 1977-01-13 | Hoechst Ag | Pyrrolidone und verfahren zu ihrer herstellung |
| DE2619638A1 (de) | 1976-05-04 | 1977-11-17 | Hoechst Ag | Pyrrolidone und verfahren zu ihrer herstellung |
| US4268522A (en) | 1976-06-14 | 1981-05-19 | Pfizer Inc. | 13,14-Dihydro-15-alkenyl- and 13,14-dihydro-15-alkynyl prostaglandins and analogs thereof |
| US4320136A (en) | 1980-08-11 | 1982-03-16 | E. I. Du Pont De Nemours And Company | 8-Aza-16,16-difluoroprostanoids |
| US6043275A (en) | 1998-04-16 | 2000-03-28 | Ono Pharmaceutical Co., Ltd. | 3,7-dithiaprostanoic acid derivative |
| US6894175B1 (en) | 1999-08-04 | 2005-05-17 | The Procter & Gamble Company | 2-Decarboxy-2-phosphinico prostaglandin derivatives and methods for their preparation and use |
| TWI247606B (en) | 1999-11-24 | 2006-01-21 | Ono Pharmaceutical Co | Treating agent for osteopenic diseases |
| GEP20043203B (en) * | 1999-12-22 | 2004-03-25 | Pfizer Prod Inc | EP4 Receptor Selective Agonists in the Treatment of Osteoporosis |
| US20010056060A1 (en) | 2000-02-07 | 2001-12-27 | Cameron Kimberly O. | Treatment of osteoporsis with EP2/EP4 receptor selective agonists |
| AU2001290250A1 (en) | 2000-09-21 | 2002-04-02 | Ono Pharmaceutical Co. Ltd. | Ep4 receptor agonists containing 8-azaprostaglandin derivatives as the active ingredient |
| OA12533A (en) | 2000-11-27 | 2006-06-05 | Pfizer Prod Inc | Ep4 receptor selective agonists in the treatment of osteoporosis. |
| CA2451392A1 (en) | 2001-07-16 | 2003-01-30 | F. Hoffmann-La Roche Ag | Prostaglandin analogues as ep4 receptor agonists |
| CN100371322C (zh) | 2001-07-16 | 2008-02-27 | 霍夫曼-拉罗奇有限公司 | 作为前列腺素类化合物激动剂的2-吡咯烷酮衍生物 |
| EP2255829A3 (en) | 2001-07-23 | 2012-03-28 | Ono Pharmaceutical Co., Ltd. | Pharmaceutical composition for treatment of diseases associated with decrease in bone mass comprising EP4 agonist as active ingredient |
| US7410991B2 (en) | 2001-10-23 | 2008-08-12 | Laboratoires Serono S.A. | Pyrazolidinone compounds as ligands of the prostaglandin EP2 and/or EP4 receptors |
| EP1461026A2 (en) | 2001-12-03 | 2004-09-29 | Merck & Co., Inc. | Method for treating ocular hypertension |
| WO2003047417A2 (en) | 2001-12-03 | 2003-06-12 | Merck & Co., Inc. | Ep4 receptor agonist, compositions and methods thereof |
| AU2003211574A1 (en) | 2002-03-05 | 2003-09-16 | Ono Pharmaceutical Co., Ltd. | 8-azaprostaglandin derivative compounds and drugs containing the compounds as the active ingredient |
| EP1490055A1 (en) | 2002-03-18 | 2004-12-29 | Pfizer Products Inc. | Use of selective ep4 receptor agonists for the treatment of liver failure, loss of patency of the ductus arteriosus, glaucoma or ocular hypertension |
| WO2003077910A1 (en) | 2002-03-18 | 2003-09-25 | Pfizer Products Inc. | Methods of treatment with selective ep4 receptor agonists |
| US6573294B1 (en) | 2002-05-14 | 2003-06-03 | Allergan, Inc. | 8-azaprostaglandin analogs as agents for lowering intraocular pressure |
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| US20060167081A1 (en) | 2002-10-25 | 2006-07-27 | Xavier Billot | Ep4 receptor agonists |
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| ES2305779T3 (es) * | 2003-03-03 | 2008-11-01 | Laboratoires Serono Sa | Derivados de g-lactama como agonistas de prostaglandinas. |
| US7169807B2 (en) | 2004-04-09 | 2007-01-30 | Allergan, Inc. | 10-Hydroxy-11-dihydroprostaglandin analogs as selective EP4 agonists |
| WO2006016695A1 (ja) | 2004-08-10 | 2006-02-16 | Ono Pharmaceutical Co., Ltd. | Ｅｐ４アゴニストを含有してなる高カリウム血症の予防および／または治療剤 |
| US7858610B2 (en) | 2004-08-10 | 2010-12-28 | Ono Pharmaceutical Co., Ltd. | Preventive and/or remedy for lower urinary tract diseases containing EP4 agonist |
| AU2006253356B2 (en) * | 2005-06-03 | 2011-12-01 | Ono Pharmaceutical Co., Ltd. | Agent for regeneration and/or protection of nerves |
| US20070232660A1 (en) | 2006-04-04 | 2007-10-04 | Allergan, Inc. | Therapeutic and delivery methods of prostaglandin ep4 agonists |
| EP2147672A4 (en) | 2007-05-08 | 2011-11-02 | Nat University Corp Hamamatsu University School Of Medicine | CYTOTOXIC T CELL ACTIVATOR WITH AN EP4 AGONIST |
| WO2009055289A2 (en) | 2007-10-23 | 2009-04-30 | Allergan, Inc. | Therapeutic substituted lactams |
| US20120270934A1 (en) * | 2009-07-03 | 2012-10-25 | Concert Pharmaceuticals, Inc. | Prostacyclin derivatives |
| CN103201261A (zh) | 2010-11-10 | 2013-07-10 | 埃科特莱茵药品有限公司 | 用作为食欲素受体拮抗剂的内酰胺衍生物 |
| US20120283293A1 (en) | 2011-05-06 | 2012-11-08 | The Board Of Trustees Of The Leland Stanford Junior University | Methods of neuroprotection involving Prostaglandin E2 EP4 (PGE2 EP4) receptor activation |
| WO2013018837A1 (ja) | 2011-08-02 | 2013-02-07 | 小野薬品工業株式会社 | 左室拡張機能改善剤 |
| WO2014015247A1 (en) | 2012-07-19 | 2014-01-23 | Cayman Chemical Company, Inc. | Difluorolactam compounds as ep4 receptor-selective agonists for use in the treatment of ep4-mediated disease and conditions |
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2014
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| IL240988A0 (en) | 2015-11-30 |
| WO2014144584A2 (en) | 2014-09-18 |
| CA2906134A1 (en) | 2014-09-18 |
| IL240988A (en) | 2017-05-29 |
| JP6317807B2 (ja) | 2018-04-25 |
| SG11201507470WA (en) | 2015-10-29 |
| AU2014228973B2 (en) | 2018-11-08 |
| AU2014228973A1 (en) | 2015-09-17 |
| HK1222170A1 (en) | 2017-06-23 |
| US9688627B2 (en) | 2017-06-27 |
| IL250077A0 (en) | 2017-03-30 |
| JP2016516050A (ja) | 2016-06-02 |
| PT2989098T (pt) | 2017-08-16 |
| JP2017186356A (ja) | 2017-10-12 |
| US20160060216A1 (en) | 2016-03-03 |
| CN105143217A (zh) | 2015-12-09 |
| EP2989098A2 (en) | 2016-03-02 |
| BR112015023080A2 (pt) | 2017-07-18 |
| JP6352497B2 (ja) | 2018-07-04 |
| EP3235817B1 (en) | 2018-12-12 |
| EA201591793A1 (ru) | 2016-01-29 |
| EP2989098B1 (en) | 2017-05-10 |
| DK2989098T3 (en) | 2017-08-28 |
| WO2014144584A3 (en) | 2014-11-20 |
| EP3235817A1 (en) | 2017-10-25 |
| KR20150130326A (ko) | 2015-11-23 |
| PH12015502165A1 (en) | 2016-01-25 |
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