CA2309135A1 - N,n-diethylglycolamido ester prodrugs of indole spla2 inhibitors - Google Patents
N,n-diethylglycolamido ester prodrugs of indole spla2 inhibitors Download PDFInfo
- Publication number
- CA2309135A1 CA2309135A1 CA002309135A CA2309135A CA2309135A1 CA 2309135 A1 CA2309135 A1 CA 2309135A1 CA 002309135 A CA002309135 A CA 002309135A CA 2309135 A CA2309135 A CA 2309135A CA 2309135 A1 CA2309135 A1 CA 2309135A1
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- Canada
- Prior art keywords
- arthritis
- compound
- methyl
- disease
- biphenyl
- 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
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- 150000002148 esters Chemical class 0.000 title claims abstract description 22
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 title abstract description 12
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- 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
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- 229940002612 prodrug Drugs 0.000 title description 9
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- 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 21
- -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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- 238000004519 manufacturing process Methods 0.000 claims 1
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- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 31
- 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
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 18
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 15
- 235000019439 ethyl acetate Nutrition 0.000 description 12
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 12
- 239000000243 solution Substances 0.000 description 11
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- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 8
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- 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
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- ZLNQQNXFFQJAID-UHFFFAOYSA-L magnesium carbonate Chemical compound [Mg+2].[O-]C([O-])=O ZLNQQNXFFQJAID-UHFFFAOYSA-L 0.000 description 1
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- YDCHPLOFQATIDS-UHFFFAOYSA-N methyl 2-bromoacetate Chemical compound COC(=O)CBr YDCHPLOFQATIDS-UHFFFAOYSA-N 0.000 description 1
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- WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 description 1
- 235000010234 sodium benzoate Nutrition 0.000 description 1
- 239000004299 sodium benzoate Substances 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
- 235000010265 sodium sulphite Nutrition 0.000 description 1
- 239000007909 solid dosage form Substances 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
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- 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
- C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
- C07D209/18—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D209/22—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals with an aralkyl radical attached to the ring nitrogen atom
-
- 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
- A61P1/18—Drugs for disorders of the alimentary tract or the digestive system for pancreatic disorders, e.g. pancreatic enzymes
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- 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
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
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- A—HUMAN NECESSITIES
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- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P19/06—Antigout agents, e.g. antihyperuricemic or uricosuric agents
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- A—HUMAN NECESSITIES
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- A—HUMAN NECESSITIES
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- A61P37/00—Drugs for immunological or allergic disorders
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- 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
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/18—Drugs for disorders of the endocrine system of the parathyroid hormones
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
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- 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
- A61P7/06—Antianaemics
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/02—Non-specific cardiovascular stimulants, e.g. drugs for syncope, antihypotensives
-
- 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)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Engineering & Computer Science (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Pulmonology (AREA)
- Heart & Thoracic Surgery (AREA)
- Physical Education & Sports Medicine (AREA)
- Diabetes (AREA)
- Rheumatology (AREA)
- Cardiology (AREA)
- Hematology (AREA)
- Pain & Pain Management (AREA)
- Immunology (AREA)
- Endocrinology (AREA)
- Dermatology (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 |
|---|---|---|---|
| US6328097P | 1997-10-27 | 1997-10-27 | |
| US60/063,280 | 1997-10-27 | ||
| PCT/US1998/022690 WO1999021546A1 (en) | 1997-10-27 | 1998-10-26 | N,N-DIETHYLGLYCOLAMIDO ESTER PRODRUGS OF INDOLE sPLA2 INHIBITORS |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2309135A1 true CA2309135A1 (en) | 1999-05-06 |
Family
ID=22048164
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002309135A Abandoned CA2309135A1 (en) | 1997-10-27 | 1998-10-26 | N,n-diethylglycolamido ester prodrugs of indole spla2 inhibitors |
Country Status (6)
| Country | Link |
|---|---|
| US (1) | US6274616B1 (https=) |
| EP (1) | EP1030661A4 (https=) |
| JP (1) | JP2001520991A (https=) |
| AU (1) | AU1279899A (https=) |
| CA (1) | CA2309135A1 (https=) |
| WO (1) | WO1999021546A1 (https=) |
Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| BR9501404A (pt) * | 1994-04-01 | 1996-03-05 | Lilly Co Eli | 1H-indol-3 glioxilamida e formulação farmacèutica |
| JP2003505372A (ja) * | 1999-07-19 | 2003-02-12 | イーライ・リリー・アンド・カンパニー | ｓＰＬＡ２インヒビター |
| US6706752B1 (en) | 1999-07-19 | 2004-03-16 | Eli Lilly And Company | sPLA2 inhibitors |
| DE60032254D1 (de) * | 1999-09-20 | 2007-01-18 | Lilly Co Eli | Hydroxyfunktionelle amid-1h-indolderivate aktiv als spla2 inhibitoren |
| US6831095B1 (en) | 1999-09-20 | 2004-12-14 | Eli Lilly And Company | Hydroxyfunctional amide 1h-indole derivatives active as sPLA2 inhibitors |
| 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 |
| NZ624963A (en) | 2009-04-29 | 2016-07-29 | Amarin Pharmaceuticals Ie Ltd | Pharmaceutical compositions comprising epa and a cardiovascular agent and methods of using the same |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| BR9501404A (pt) * | 1994-04-01 | 1996-03-05 | Lilly Co Eli | 1H-indol-3 glioxilamida e formulação farmacèutica |
| US5641800A (en) * | 1994-07-21 | 1997-06-24 | Eli Lilly And Company | 1H-indole-1-functional sPLA2 inhibitors |
| US5972988A (en) * | 1997-03-26 | 1999-10-26 | Eli Lilly And Company | Method for treatment of chronic bronchitis using indole compounds |
| AU1200799A (en) * | 1997-10-27 | 1999-05-17 | Eli Lilly And Company | Isopropyl ester prodrugs of indole spla2 inhibitors |
-
1998
- 1998-10-26 CA CA002309135A patent/CA2309135A1/en not_active Abandoned
- 1998-10-26 WO PCT/US1998/022690 patent/WO1999021546A1/en not_active Ceased
- 1998-10-26 AU AU12798/99A patent/AU1279899A/en not_active Abandoned
- 1998-10-26 JP JP2000517704A patent/JP2001520991A/ja not_active Withdrawn
- 1998-10-26 EP EP98956223A patent/EP1030661A4/en not_active Withdrawn
-
2000
- 2000-03-29 US US09/509,754 patent/US6274616B1/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| JP2001520991A (ja) | 2001-11-06 |
| WO1999021546A1 (en) | 1999-05-06 |
| US6274616B1 (en) | 2001-08-14 |
| AU1279899A (en) | 1999-05-17 |
| EP1030661A1 (en) | 2000-08-30 |
| EP1030661A4 (en) | 2002-07-17 |
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