CA2308443A1 - Morpholino-n-ethyl ester prodrugs of indole spla2 inhibitors - Google Patents
Morpholino-n-ethyl ester prodrugs of indole spla2 inhibitors Download PDFInfo
- Publication number
- CA2308443A1 CA2308443A1 CA002308443A CA2308443A CA2308443A1 CA 2308443 A1 CA2308443 A1 CA 2308443A1 CA 002308443 A CA002308443 A CA 002308443A CA 2308443 A CA2308443 A CA 2308443A CA 2308443 A1 CA2308443 A1 CA 2308443A1
- Authority
- CA
- Canada
- Prior art keywords
- arthritis
- compound
- methyl
- disease
- ylmethyl
- 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.)
- Abandoned
Links
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 title abstract description 12
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 title abstract description 8
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 title abstract description 8
- 239000003112 inhibitor Substances 0.000 title description 25
- 239000000651 prodrug Substances 0.000 title description 8
- 229940002612 prodrug Drugs 0.000 title description 8
- 150000001875 compounds Chemical class 0.000 claims abstract description 56
- 102000005473 Secretory Phospholipases A2 Human genes 0.000 claims abstract description 36
- 108010031873 Secretory Phospholipases A2 Proteins 0.000 claims abstract description 36
- CXAFWBHDYGONMZ-UHFFFAOYSA-N 2-[2-methyl-3-oxamoyl-1-[(3-phenylphenyl)methyl]indol-4-yl]oxyacetic acid Chemical compound CC1=C(C(=O)C(N)=O)C2=C(OCC(O)=O)C=CC=C2N1CC(C=1)=CC=CC=1C1=CC=CC=C1 CXAFWBHDYGONMZ-UHFFFAOYSA-N 0.000 claims abstract description 24
- -1 indole compound Chemical class 0.000 claims abstract description 10
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- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 claims description 3
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- AWMLDBKLOPNOAR-UHFFFAOYSA-N indole-3-glyoxylamide Natural products C1=CC=C2C(C(=O)C(=O)N)=CNC2=C1 AWMLDBKLOPNOAR-UHFFFAOYSA-N 0.000 claims description 2
- 230000001225 therapeutic effect Effects 0.000 claims description 2
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- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 29
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 21
- 239000000203 mixture Substances 0.000 description 19
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 15
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 15
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 12
- 235000019439 ethyl acetate Nutrition 0.000 description 11
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- 150000002148 esters Chemical group 0.000 description 9
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 8
- 239000003814 drug Substances 0.000 description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 8
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Chemical compound OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 7
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- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
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- QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 4
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- 239000002502 liposome Substances 0.000 description 1
- WGOPGODQLGJZGL-UHFFFAOYSA-N lithium;butane Chemical compound [Li+].CC[CH-]C WGOPGODQLGJZGL-UHFFFAOYSA-N 0.000 description 1
- 239000006210 lotion Substances 0.000 description 1
- ZLNQQNXFFQJAID-UHFFFAOYSA-L magnesium carbonate Chemical compound [Mg+2].[O-]C([O-])=O ZLNQQNXFFQJAID-UHFFFAOYSA-L 0.000 description 1
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- COPHUROCEVYXDJ-UHFFFAOYSA-N methyl 2-[2-methyl-3-oxamoyl-1-[(3-phenylphenyl)methyl]indol-4-yl]oxyacetate Chemical compound CC1=C(C(=O)C(N)=O)C=2C(OCC(=O)OC)=CC=CC=2N1CC(C=1)=CC=CC=1C1=CC=CC=C1 COPHUROCEVYXDJ-UHFFFAOYSA-N 0.000 description 1
- YDCHPLOFQATIDS-UHFFFAOYSA-N methyl 2-bromoacetate Chemical compound COC(=O)CBr YDCHPLOFQATIDS-UHFFFAOYSA-N 0.000 description 1
- 150000004702 methyl esters Chemical class 0.000 description 1
- 239000000693 micelle Substances 0.000 description 1
- HPNSFSBZBAHARI-UHFFFAOYSA-N micophenolic acid Natural products OC1=C(CC=C(C)CCC(O)=O)C(OC)=C(C)C2=C1C(=O)OC2 HPNSFSBZBAHARI-UHFFFAOYSA-N 0.000 description 1
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- UEUXEKPTXMALOB-UHFFFAOYSA-J tetrasodium;2-[2-[bis(carboxylatomethyl)amino]ethyl-(carboxylatomethyl)amino]acetate Chemical compound [Na+].[Na+].[Na+].[Na+].[O-]C(=O)CN(CC([O-])=O)CCN(CC([O-])=O)CC([O-])=O UEUXEKPTXMALOB-UHFFFAOYSA-J 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/30—Indoles; Hydrogenated indoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to carbon atoms of the hetero ring
- C07D209/42—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- 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
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/06—Antiasthmatics
-
- 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
-
- 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
- A61P19/06—Antigout agents, e.g. antihyperuricemic or uricosuric agents
-
- 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]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Rheumatology (AREA)
- Pulmonology (AREA)
- Pain & Pain Management (AREA)
- Physical Education & Sports Medicine (AREA)
- Hematology (AREA)
- Diabetes (AREA)
- Immunology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Indole Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US6364697P | 1997-10-27 | 1997-10-27 | |
| US60/063,646 | 1997-10-27 | ||
| PCT/US1998/022679 WO1999021559A1 (en) | 1997-10-27 | 1998-10-26 | MORPHOLINO-N-ETHYL ESTER PRODRUGS OF INDOLE sPLA2 INHIBITORS |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2308443A1 true CA2308443A1 (en) | 1999-05-06 |
Family
ID=22050578
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002308443A Abandoned CA2308443A1 (en) | 1997-10-27 | 1998-10-26 | Morpholino-n-ethyl ester prodrugs of indole spla2 inhibitors |
Country Status (9)
| Country | Link |
|---|---|
| US (1) | US6177426B1 (enExample) |
| EP (1) | EP1039911B1 (enExample) |
| JP (1) | JP2001520998A (enExample) |
| AT (1) | ATE296286T1 (enExample) |
| AU (1) | AU1200899A (enExample) |
| CA (1) | CA2308443A1 (enExample) |
| DE (1) | DE69830335T2 (enExample) |
| ES (1) | ES2241178T3 (enExample) |
| WO (1) | WO1999021559A1 (enExample) |
Families Citing this family (26)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU1200899A (en) | 1997-10-27 | 1999-05-17 | Eli Lilly And Company | Morpholino-n-ethyl ester prodrugs of indole spla2 inhibitors |
| US6274578B1 (en) | 1999-04-20 | 2001-08-14 | Eli Lilly And Company | sPLA2 inhibitor ester |
| US6140327A (en) * | 1999-05-12 | 2000-10-31 | Eli Lilly And Company | Morpholino-n-ethyl ester derivative of an indole sPLA2 inhibitor |
| DE60032774D1 (de) * | 1999-07-19 | 2007-02-15 | Lilly Co Eli | Spla2 inhibitoren |
| US6706752B1 (en) | 1999-07-19 | 2004-03-16 | Eli Lilly And Company | sPLA2 inhibitors |
| US6831095B1 (en) | 1999-09-20 | 2004-12-14 | Eli Lilly And Company | Hydroxyfunctional amide 1h-indole derivatives active as sPLA2 inhibitors |
| DE60032254D1 (de) * | 1999-09-20 | 2007-01-18 | Lilly Co Eli | Hydroxyfunktionelle amid-1h-indolderivate aktiv als spla2 inhibitoren |
| DE19962300A1 (de) * | 1999-12-23 | 2001-06-28 | Asta Medica Ag | Substituierte N-Benzyl-Indol-3-yl-glyoxylsäure-Derivate mit Antitumorwirkung |
| EP1303262A2 (en) * | 2000-07-14 | 2003-04-23 | Eli Lilly And Company | Use of a spla2 inhibitor for the treatment of sepsis |
| US20030124174A1 (en) * | 2001-10-25 | 2003-07-03 | Endo Pharmaceuticals, Inc | Method for treating non-neuropathic pain |
| AUPS282602A0 (en) | 2002-06-07 | 2002-06-27 | Garvan Institute Of Medical Research | Method of inhibiting cell proliferation |
| EP4008327A1 (en) | 2009-04-29 | 2022-06-08 | Amarin Pharmaceuticals Ireland Limited | Pharmaceutical compositions comprising epa and a cardiovascular agent and methods of using the same |
| EP2887934A1 (en) * | 2012-08-22 | 2015-07-01 | XenoPort, Inc. | Methods of administering monomethyl fumarate and prodrugs thereof having reduced side effects |
| US20140348915A9 (en) | 2012-08-22 | 2014-11-27 | Xenoport, Inc. | Oral Dosage Forms of Methyl Hydrogen Fumarate and Prodrugs Thereof |
| US10179118B2 (en) | 2013-03-24 | 2019-01-15 | Arbor Pharmaceuticals, Llc | Pharmaceutical compositions of dimethyl fumarate |
| US9421182B2 (en) | 2013-06-21 | 2016-08-23 | Xenoport, Inc. | Cocrystals of dimethyl fumarate |
| US9416096B2 (en) | 2013-09-06 | 2016-08-16 | Xenoport, Inc. | Crystalline forms of (N,N-Diethylcarbamoyl)methyl methyl (2E)but-2-ene-1,4-dioate, methods of synthesis and use |
| US9999672B2 (en) | 2014-03-24 | 2018-06-19 | Xenoport, Inc. | Pharmaceutical compositions of fumaric acid esters |
| JOP20160086B1 (ar) | 2015-05-08 | 2021-08-17 | 2 Katholieke Univ Leuven Ku Leuven Research And Development | مشتقات اندول مستبدلة احاديا او ثنائيا بصفتها مانعات للتكاثر الفيروسي لحمى الفنك |
| JOP20160198B1 (ar) * | 2015-09-16 | 2022-03-14 | Janssen Pharmaceuticals Inc | مشتقات اندول مستبدلة احاديا او ثنائيا بصفتها مانعات للتكاثر الفيروسي لحمى الفنك |
| CA3013407A1 (en) | 2016-03-31 | 2017-10-05 | Janssen Pharmaceuticals, Inc. | Substituted indoline derivatives as dengue viral replication inhibitors |
| JOP20170069B1 (ar) | 2016-04-01 | 2021-08-17 | 1 Janssen Pharmaceuticals Inc | مشتقات اندولين مستبدلة بصفتها مانعات للتكاثر الفيروسي لحمى الفنك |
| JOP20180026A1 (ar) | 2017-03-31 | 2019-01-30 | Univ Leuven Kath | مشتقات اندولين مستبدلة بصفتها مانعات للتكاثر الفيروسي لحمى الفنك |
| JOP20180025B1 (ar) | 2017-03-31 | 2021-08-17 | Janssen Pharmaceuticals Inc | مشتقات اندولين مستبدلة بصفتها مانعات للتكاثر الفيروسي لحمى الفنك |
| EA201992782A1 (ru) | 2017-05-22 | 2020-03-24 | Янссен Фармасьютикалз, Инк. | Замещенные производные индолина в качестве ингибиторов репликации вирусов денге |
| EA039702B1 (ru) | 2017-05-22 | 2022-03-01 | Янссен Фармасьютикалз, Инк. | Замещенные производные индолина в качестве ингибиторов репликации вирусов денге |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ATE220394T1 (de) | 1994-04-01 | 2002-07-15 | Lilly Co Eli | 1h-indol-3-glyoxylamid spla2 inhibitoren |
| US5972988A (en) | 1997-03-26 | 1999-10-26 | Eli Lilly And Company | Method for treatment of chronic bronchitis using indole compounds |
| AU1200899A (en) | 1997-10-27 | 1999-05-17 | Eli Lilly And Company | Morpholino-n-ethyl ester prodrugs of indole spla2 inhibitors |
| AU1200799A (en) * | 1997-10-27 | 1999-05-17 | Eli Lilly And Company | Isopropyl ester prodrugs of indole spla2 inhibitors |
| CA2310249A1 (en) | 1997-11-14 | 1999-05-27 | August Masaru Watanabe | Treatment for alzheimer's disease |
-
1998
- 1998-10-26 AU AU12008/99A patent/AU1200899A/en not_active Abandoned
- 1998-10-26 DE DE69830335T patent/DE69830335T2/de not_active Expired - Fee Related
- 1998-10-26 JP JP2000517717A patent/JP2001520998A/ja not_active Withdrawn
- 1998-10-26 WO PCT/US1998/022679 patent/WO1999021559A1/en not_active Ceased
- 1998-10-26 ES ES98955125T patent/ES2241178T3/es not_active Expired - Lifetime
- 1998-10-26 US US09/509,755 patent/US6177426B1/en not_active Expired - Fee Related
- 1998-10-26 CA CA002308443A patent/CA2308443A1/en not_active Abandoned
- 1998-10-26 EP EP98955125A patent/EP1039911B1/en not_active Expired - Lifetime
- 1998-10-26 AT AT98955125T patent/ATE296286T1/de not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| ATE296286T1 (de) | 2005-06-15 |
| US6177426B1 (en) | 2001-01-23 |
| WO1999021559A1 (en) | 1999-05-06 |
| EP1039911B1 (en) | 2005-05-25 |
| JP2001520998A (ja) | 2001-11-06 |
| AU1200899A (en) | 1999-05-17 |
| EP1039911A1 (en) | 2000-10-04 |
| DE69830335T2 (de) | 2006-02-02 |
| EP1039911A4 (en) | 2002-07-17 |
| ES2241178T3 (es) | 2005-10-16 |
| DE69830335D1 (de) | 2005-06-30 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FZDE | Discontinued |