DE60214713T2 - Arylborsäuren für die behandlung von fettsucht - Google Patents
Arylborsäuren für die behandlung von fettsucht Download PDFInfo
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- DE60214713T2 DE60214713T2 DE60214713T DE60214713T DE60214713T2 DE 60214713 T2 DE60214713 T2 DE 60214713T2 DE 60214713 T DE60214713 T DE 60214713T DE 60214713 T DE60214713 T DE 60214713T DE 60214713 T2 DE60214713 T2 DE 60214713T2
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- substituted
- amine
- ammonium
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- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 34
- -1 phenyl boronic acid compound Chemical class 0.000 claims abstract description 32
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 31
- 125000001183 hydrocarbyl group Chemical group 0.000 claims abstract description 24
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- 125000000217 alkyl group Chemical group 0.000 claims abstract description 14
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- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
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- JAJWGJBVLPIOOH-IZYKLYLVSA-M sodium taurocholate Chemical compound [Na+].C([C@H]1C[C@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(=O)NCCS([O-])(=O)=O)C)[C@@]2(C)[C@@H](O)C1 JAJWGJBVLPIOOH-IZYKLYLVSA-M 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F5/00—Compounds containing elements of Groups 3 or 13 of the Periodic Table
- C07F5/02—Boron compounds
- C07F5/025—Boronic and borinic acid compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/74—Synthetic polymeric materials
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/74—Synthetic polymeric materials
- A61K31/785—Polymers containing nitrogen
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/04—Anorexiants; Antiobesity agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/06—Antihyperlipidemics
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Epidemiology (AREA)
- Diabetes (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Child & Adolescent Psychology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US30208101P | 2001-06-29 | 2001-06-29 | |
| US302081P | 2001-06-29 | ||
| US35946702P | 2002-02-22 | 2002-02-22 | |
| US359467P | 2002-02-22 | ||
| PCT/US2002/020923 WO2003002570A1 (en) | 2001-06-29 | 2002-07-01 | Aryl boronic acids for treating obesity |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| DE60214713D1 DE60214713D1 (de) | 2006-10-26 |
| DE60214713T2 true DE60214713T2 (de) | 2007-09-06 |
Family
ID=26972758
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE60214713T Expired - Fee Related DE60214713T2 (de) | 2001-06-29 | 2002-07-01 | Arylborsäuren für die behandlung von fettsucht |
Country Status (12)
| Country | Link |
|---|---|
| US (3) | US6858592B2 (enExample) |
| EP (1) | EP1404685B1 (enExample) |
| JP (1) | JP2004535452A (enExample) |
| AT (1) | ATE339426T1 (enExample) |
| AU (2) | AU2002316499B2 (enExample) |
| CA (1) | CA2489681A1 (enExample) |
| CY (1) | CY1105829T1 (enExample) |
| DE (1) | DE60214713T2 (enExample) |
| DK (1) | DK1404685T3 (enExample) |
| ES (1) | ES2275888T3 (enExample) |
| PT (1) | PT1404685E (enExample) |
| WO (1) | WO2003002570A1 (enExample) |
Families Citing this family (25)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7041280B2 (en) * | 2001-06-29 | 2006-05-09 | Genzyme Corporation | Aryl boronate functionalized polymers for treating obesity |
| US6858592B2 (en) * | 2001-06-29 | 2005-02-22 | Genzyme Corporation | Aryl boronic acids for treating obesity |
| WO2003105860A1 (en) * | 2002-06-14 | 2003-12-24 | Novo Nordisk A/S | Pharmaceutical use of boronic acids and esters thereof |
| AU2003291567A1 (en) * | 2002-11-19 | 2004-06-15 | Genzyme Corporation | Polymeric boronic acid derivatives as lipase inhibitors |
| JP2008519853A (ja) * | 2004-11-12 | 2008-06-12 | トラスティーズ オブ タフツ カレッジ | リパーゼ阻害物質 |
| WO2006098270A1 (ja) * | 2005-03-14 | 2006-09-21 | Eisai R & D Management Co., Ltd. | オキシメチルホウ素化合物 |
| US7622492B2 (en) | 2005-08-31 | 2009-11-24 | Hoffmann-La Roche Inc. | Pyrazolones as inhibitors of 11β-hydroxysteroid dehydrogenase |
| US10157355B2 (en) | 2005-11-15 | 2018-12-18 | General Electric Company | Method to view schedule interdependencies and provide proactive clinical process decision support in day view form |
| US7801058B2 (en) * | 2006-07-27 | 2010-09-21 | Mobitrum Corporation | Method and system for dynamic information exchange on mesh network devices |
| JO3598B1 (ar) * | 2006-10-10 | 2020-07-05 | Infinity Discovery Inc | الاحماض والاسترات البورونية كمثبطات اميد هيدروليز الحامض الدهني |
| CA2731645C (en) * | 2007-07-24 | 2017-05-23 | The University Of British Columbia | Substituted aryl-fluoroborates as imaging agents |
| EP2282742A1 (en) * | 2008-04-09 | 2011-02-16 | Infinity Pharmaceuticals, Inc. | Inhibitors of fatty acid amide hydrolase |
| WO2010118155A1 (en) | 2009-04-07 | 2010-10-14 | Infinity Pharmaceuticals, Inc. | Inhibitors of fatty acid amide hydrolase |
| JP2012523425A (ja) | 2009-04-07 | 2012-10-04 | インフイニトイ プハルマセウトイカルス インコーポレイテッド | 脂肪酸アミドヒドロラーゼの阻害薬 |
| US8709489B2 (en) | 2009-09-30 | 2014-04-29 | Surmodics, Inc. | Emulsions containing arylboronic acids and medical articles made therefrom |
| BR112012019120A2 (pt) * | 2010-02-03 | 2016-06-28 | Infinity Pharmaceuticais Inc | forma sólida, composição farmacêutica, método de preparação do composto 1, método de tratamento de uma condição mediada por faah |
| US8546617B1 (en) | 2012-03-23 | 2013-10-01 | Empire Technology Development Llc | Dioxaborinanes and uses thereof |
| US9120938B2 (en) | 2012-07-31 | 2015-09-01 | Empire Technology Development Llc | Polymerizable organoboron alkyd resin anti fouling coatings |
| WO2014021845A1 (en) * | 2012-07-31 | 2014-02-06 | Empire Technology Development Llc | Polymerizable organoboron alkyd resin anti fouling coatings |
| ES2618374T3 (es) * | 2012-10-17 | 2017-06-21 | Board Of Supervisors Of Louisiana State University And Agricultural And Mechanical College | Composiciones y métodos para mejorar la absorción de glucosa |
| EP2964658B1 (en) | 2013-03-08 | 2024-08-07 | The University Of British Columbia | Positron-emitting substituted organofluoroborates as imaging agents |
| US11078528B2 (en) | 2015-10-12 | 2021-08-03 | Advanced Cell Diagnostics, Inc. | In situ detection of nucleotide variants in high noise samples, and compositions and methods related thereto |
| CN106243343B (zh) * | 2016-08-11 | 2018-04-03 | 江苏大学 | 一种苯硼酸功能化嵌段聚合物的合成及应用 |
| US12427209B2 (en) | 2018-12-18 | 2025-09-30 | Provincial Health Services Authority | Dual mode 18F-labelled theranostic compounds and uses thereof |
| AU2022245308A1 (en) * | 2021-03-24 | 2023-09-21 | Trustees Of Tufts College | Boronic acid compounds, compositions and methods |
Family Cites Families (52)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4496722A (en) * | 1981-05-01 | 1985-01-29 | The Children's Medical Center Corporation | Reporter compounds |
| GB8819224D0 (en) | 1988-08-12 | 1988-09-14 | Merck Patent Gmbh | Process for preparation of rod-like compounds |
| DE3930663C1 (en) | 1989-09-14 | 1990-11-15 | Merck Patent Gmbh, 6100 Darmstadt, De | Cross-coupling metal organic cpds. and e.g. halogen cpds. - includes using transition metal-palladium catalyst and opt. metal alcoholate |
| EP0478050A1 (en) | 1990-09-24 | 1992-04-01 | Unilever N.V. | Detergent composition |
| GB9024775D0 (en) | 1990-11-14 | 1991-01-02 | Axis Research | Chemical compounds |
| IE914573A1 (en) | 1991-01-17 | 1992-07-29 | Ici Plc | Boron compounds |
| HUT65823A (en) * | 1991-04-30 | 1994-07-28 | Procter & Gamble | Liquid detergents with an aryl boronic acid and process for using thereof |
| GB9119920D0 (en) * | 1991-09-18 | 1991-10-30 | Glaxo Group Ltd | Chemical compounds |
| CH683522A5 (de) | 1992-03-13 | 1994-03-31 | Hoffmann La Roche | Verfahren zur Herstellung von Diarylen. |
| JP3257029B2 (ja) | 1992-04-22 | 2002-02-18 | 日本油脂株式会社 | フェニルボロン酸誘導体及び製造方法 |
| CA2096496A1 (en) | 1992-05-29 | 1993-11-30 | Bradley C. Pearce | Acyclic tocotrienol analogs in the treatment of hypercholesterolemia and hyperlipidemia |
| US5290817A (en) * | 1992-06-09 | 1994-03-01 | The Du Pont Merck Pharmaceutical Co. | Substituted 1-benzylindanes and their use as inhibitors of phospholipase A2 |
| WO1994014803A1 (en) | 1992-12-21 | 1994-07-07 | Zeneca Limited | Quinuclidine derivatives as squalene synthase inhibitors |
| GB2276162A (en) | 1993-03-17 | 1994-09-21 | Glaxo Group Ltd | Aniline and benazilide derivatives |
| US5776951A (en) | 1993-06-30 | 1998-07-07 | Glaxo Wellcome Inc. | Anti-atherosclerotic diaryl compounds |
| AU7121394A (en) * | 1993-07-09 | 1995-02-06 | Borax Consolidated Ltd | Boronic acid or borinic acid derivatives as enzyme stabilizers |
| JP3412198B2 (ja) * | 1993-08-31 | 2003-06-03 | 日本油脂株式会社 | 変性マレイン酸共重合体および用途 |
| JPH09503773A (ja) | 1993-10-19 | 1997-04-15 | スミスクライン・ビーチャム・パブリック・リミテッド・カンパニー | ５ｈｔ−１ｄレセプター拮抗剤用のベンズアニリド誘導体 |
| EP0741693B1 (en) | 1994-01-27 | 1999-03-24 | Novartis AG | Process for the preparation of arylacetic ester derivatives via palladium-catalyzed cross coupling reaction |
| US5631364A (en) * | 1994-03-31 | 1997-05-20 | Axis Biochemicals Asa | Labelled boronic acid derivatives |
| SI9400289A (en) | 1994-07-13 | 1996-02-29 | Ponikvar Jadranka Buturovic | A method for preventing blood coagulation in a haemodialysis circuit or haemodialysis analogy procedure in the extra-body circuit. |
| WO1996017833A1 (en) | 1994-12-09 | 1996-06-13 | Smithkline Beecham Corporation | Bicyclic fibrinogen antagonists |
| FI972896A7 (fi) | 1995-01-09 | 1997-07-08 | Novo Nordisk As | Nestemäisten entsyymikoostumusten stabilointi |
| US6008219A (en) | 1995-03-27 | 1999-12-28 | Smithkline Beech P.L.C. | Bicyclic amine derivatives and their use as anti-psychotic agents |
| UA58494C2 (uk) * | 1995-06-07 | 2003-08-15 | Зенека Лімітед | Похідні n-гетероарилпіридинсульфонаміду, фармацевтична композиція, спосіб одержання та спосіб протидії впливам ендотеліну |
| WO1996041859A1 (en) * | 1995-06-13 | 1996-12-27 | Novo Nordisk A/S | 4-substituted-phenyl-boronic acids as enzyme stabilizers |
| US5631371A (en) * | 1995-11-22 | 1997-05-20 | Bayer Corporation | Method for the preparation of substituted 3-(phenylimino)-3H-phenothiazines and phenoxazines |
| GB9603137D0 (en) | 1996-02-15 | 1996-04-17 | Merck Sharp & Dohme | Therapeutic agents |
| AU5446098A (en) | 1996-11-21 | 1998-06-10 | Lawrence Livermore National Laboratory | Detection of biological molecules using boronate-based chemical amplification and optical sensors |
| JP2001526643A (ja) | 1997-04-18 | 2001-12-18 | スミスクライン・ビーチャム・パブリック・リミテッド・カンパニー | ５ｈｔ１ａ、５ｈｔ１ｂおよび５ｈｔ１ｄ受容体アンタゴニスト活性を合わせ持つ化合物を含む二環式アリールまたは二環式複素環 |
| JP2002504122A (ja) | 1997-06-13 | 2002-02-05 | ノースウエスタン ユニバーシティー | ベータラクタマーゼ阻害剤及びその使用方法 |
| US6184363B1 (en) * | 1997-06-13 | 2001-02-06 | Northwestern University | Inhibitors of β-lactamases and uses therefor |
| JP2002510328A (ja) | 1997-07-25 | 2002-04-02 | スミスクライン・ビーチャム・コーポレイション | ビトロネクチン受容体アンタゴニスト |
| CO5011067A1 (es) | 1997-11-03 | 2001-02-28 | Novartis Ag | Derivados de bifenilo como productos farmaceuticos, su pre- paracion y composiciones farmaceuticas que los contienen |
| US6264937B1 (en) * | 1998-01-09 | 2001-07-24 | Geltex Pharmaceuticals, Inc. | Fat-binding polymers |
| WO1999047474A1 (en) | 1998-03-18 | 1999-09-23 | Ciba Specialty Chemicals Holding Inc. | Coupling reactions with palladium catalysts |
| AU5235599A (en) | 1998-07-31 | 2000-02-21 | Eli Lilly And Company | N-substituted sulfonamide derivatives |
| EP1112262B1 (en) | 1998-09-09 | 2004-08-04 | Inflazyme Pharmaceuticals Ltd. | Substituted gamma-phenyl-delta-lactones and analogs thereof and uses related thereto |
| GB9824310D0 (en) | 1998-11-05 | 1998-12-30 | Univ London | Activators of soluble guanylate cyclase |
| GB9824579D0 (en) | 1998-11-10 | 1999-01-06 | Novartis Ag | Organic compounds |
| DE19857765A1 (de) * | 1998-12-15 | 2000-06-21 | Clariant Gmbh | Verfahren zur Herstellung von para-Oxadiazolyl-phenyl-boronsäuren |
| WO2000035904A1 (en) | 1998-12-16 | 2000-06-22 | Northwestern University | INHIBITORS OF β-LACTAMASES AND USES THEREFOR |
| WO2000042213A1 (en) | 1999-01-13 | 2000-07-20 | The Research Foundation Of State University Of New York | A novel method for designing protein kinase inhibitors |
| BRPI0011172B8 (pt) | 1999-04-14 | 2021-05-25 | Pacific Corp | derivados do 4,5-diaril-3(2h)-furanona como inibidores de ciclooxigenase-2 |
| JP4507294B2 (ja) | 1999-05-27 | 2010-07-21 | チッソ株式会社 | ビアリール誘導体の製造方法 |
| CA2315614C (en) | 1999-07-29 | 2004-11-02 | Pfizer Inc. | Pyrazoles |
| US6566372B1 (en) | 1999-08-27 | 2003-05-20 | Ligand Pharmaceuticals Incorporated | Bicyclic androgen and progesterone receptor modulator compounds and methods |
| CN1285601C (zh) | 2000-11-30 | 2006-11-22 | 佳能株式会社 | 发光器件和显示器 |
| JP3589450B2 (ja) | 2001-03-13 | 2004-11-17 | 独立行政法人 科学技術振興機構 | アミド脱水縮合触媒として有用なパーフルオロアルキルフェニルホウ酸 |
| US6858592B2 (en) * | 2001-06-29 | 2005-02-22 | Genzyme Corporation | Aryl boronic acids for treating obesity |
| WO2003106384A2 (en) | 2002-06-01 | 2003-12-24 | Johns Hopkins University | Novel boronic chalcone derivatives and uses thereof |
| US7045652B2 (en) * | 2002-07-03 | 2006-05-16 | Pfizer Inc | Processes for preparing substituted aryl boronic acids |
-
2002
- 2002-06-27 US US10/187,397 patent/US6858592B2/en not_active Expired - Lifetime
- 2002-07-01 WO PCT/US2002/020923 patent/WO2003002570A1/en not_active Ceased
- 2002-07-01 PT PT02746808T patent/PT1404685E/pt unknown
- 2002-07-01 DE DE60214713T patent/DE60214713T2/de not_active Expired - Fee Related
- 2002-07-01 CA CA002489681A patent/CA2489681A1/en not_active Abandoned
- 2002-07-01 EP EP02746808A patent/EP1404685B1/en not_active Expired - Lifetime
- 2002-07-01 DK DK02746808T patent/DK1404685T3/da active
- 2002-07-01 ES ES02746808T patent/ES2275888T3/es not_active Expired - Lifetime
- 2002-07-01 JP JP2003508951A patent/JP2004535452A/ja active Pending
- 2002-07-01 AT AT02746808T patent/ATE339426T1/de not_active IP Right Cessation
- 2002-07-01 AU AU2002316499A patent/AU2002316499B2/en not_active Ceased
-
2004
- 2004-12-30 US US11/027,643 patent/US7049304B2/en not_active Expired - Lifetime
-
2005
- 2005-10-05 AU AU2005220192A patent/AU2005220192A1/en not_active Abandoned
-
2006
- 2006-01-31 US US11/343,598 patent/US7456156B2/en not_active Expired - Fee Related
- 2006-12-05 CY CY20061101748T patent/CY1105829T1/el unknown
Also Published As
| Publication number | Publication date |
|---|---|
| DK1404685T3 (da) | 2007-01-22 |
| US7049304B2 (en) | 2006-05-23 |
| ATE339426T1 (de) | 2006-10-15 |
| US20030064963A1 (en) | 2003-04-03 |
| US6858592B2 (en) | 2005-02-22 |
| DE60214713D1 (de) | 2006-10-26 |
| EP1404685B1 (en) | 2006-09-13 |
| CY1105829T1 (el) | 2011-02-02 |
| WO2003002570A1 (en) | 2003-01-09 |
| JP2004535452A (ja) | 2004-11-25 |
| US7456156B2 (en) | 2008-11-25 |
| US20060128664A1 (en) | 2006-06-15 |
| PT1404685E (pt) | 2007-01-31 |
| CA2489681A1 (en) | 2003-01-09 |
| HK1065046A1 (en) | 2005-02-08 |
| AU2002316499B2 (en) | 2005-08-04 |
| EP1404685A1 (en) | 2004-04-07 |
| US20050107336A1 (en) | 2005-05-19 |
| ES2275888T3 (es) | 2007-06-16 |
| AU2005220192A1 (en) | 2005-12-01 |
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