ES2275888T3 - Acidos aril-boronicos para el tratamiento de la obesidad. - Google Patents
Acidos aril-boronicos para el tratamiento de la obesidad. Download PDFInfo
- Publication number
- ES2275888T3 ES2275888T3 ES02746808T ES02746808T ES2275888T3 ES 2275888 T3 ES2275888 T3 ES 2275888T3 ES 02746808 T ES02746808 T ES 02746808T ES 02746808 T ES02746808 T ES 02746808T ES 2275888 T3 ES2275888 T3 ES 2275888T3
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- Spain
- Prior art keywords
- group
- substituted
- compound
- unsubstituted
- ammonium
- 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
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- 208000008589 Obesity Diseases 0.000 title claims description 17
- 235000020824 obesity Nutrition 0.000 title claims description 17
- 239000002253 acid Substances 0.000 title description 38
- 150000007513 acids Chemical class 0.000 title description 5
- 150000001875 compounds Chemical class 0.000 claims abstract description 65
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 48
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims abstract description 42
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 30
- 125000001183 hydrocarbyl group Chemical group 0.000 claims abstract description 25
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 claims abstract description 22
- 230000021615 conjugation Effects 0.000 claims abstract description 16
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 12
- 150000002367 halogens Chemical class 0.000 claims abstract description 12
- 150000003839 salts Chemical class 0.000 claims abstract description 10
- 150000003568 thioethers Chemical class 0.000 claims abstract description 10
- 150000001412 amines Chemical class 0.000 claims abstract description 9
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 9
- 125000003277 amino group Chemical group 0.000 claims abstract description 6
- 125000000843 phenylene group Chemical group C1(=C(C=CC=C1)*)* 0.000 claims abstract description 6
- XYFCBTPGUUZFHI-UHFFFAOYSA-O phosphonium Chemical compound [PH4+] XYFCBTPGUUZFHI-UHFFFAOYSA-O 0.000 claims abstract description 4
- 150000003573 thiols Chemical class 0.000 claims abstract description 4
- -1 -CF 3 Chemical class 0.000 claims description 40
- 239000003814 drug Substances 0.000 claims description 17
- 125000000217 alkyl group Chemical group 0.000 claims description 16
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- 125000003118 aryl group Chemical group 0.000 claims description 11
- 239000008194 pharmaceutical composition Substances 0.000 claims description 10
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical group CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 claims description 10
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- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 9
- 125000001931 aliphatic group Chemical group 0.000 claims description 8
- 150000002632 lipids Chemical class 0.000 claims description 6
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 claims description 5
- 125000002947 alkylene group Chemical group 0.000 claims description 5
- 125000000547 substituted alkyl group Chemical group 0.000 claims description 5
- 125000005208 trialkylammonium group Chemical group 0.000 claims description 5
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 claims description 4
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 claims description 4
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- 206010011091 Coronary artery thrombosis Diseases 0.000 claims description 2
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- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 claims description 2
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- 102000004877 Insulin Human genes 0.000 claims description 2
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- 229910019142 PO4 Inorganic materials 0.000 claims description 2
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- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 claims description 2
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- 229940072107 ascorbate Drugs 0.000 claims description 2
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- 208000000509 infertility Diseases 0.000 claims description 2
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- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 claims description 2
- 239000010452 phosphate Substances 0.000 claims description 2
- 208000002815 pulmonary hypertension Diseases 0.000 claims description 2
- 201000002859 sleep apnea Diseases 0.000 claims description 2
- 208000011580 syndromic disease Diseases 0.000 claims description 2
- 230000004584 weight gain Effects 0.000 claims description 2
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- 150000003841 chloride salts Chemical class 0.000 claims 2
- 206010052805 Drug tolerance decreased Diseases 0.000 claims 1
- 208000034991 Hiatal Hernia Diseases 0.000 claims 1
- 241000469204 Mellita Species 0.000 claims 1
- 201000010099 disease Diseases 0.000 claims 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 1
- 230000002526 effect on cardiovascular system Effects 0.000 claims 1
- 125000001153 fluoro group Chemical group F* 0.000 claims 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 abstract description 4
- 229910004727 OSO3H Inorganic materials 0.000 abstract 1
- 229910006069 SO3H Inorganic materials 0.000 abstract 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 abstract 1
- 239000000243 solution Substances 0.000 description 63
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 51
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 49
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 42
- 239000011541 reaction mixture Substances 0.000 description 39
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 36
- 230000015572 biosynthetic process Effects 0.000 description 35
- 239000000203 mixture Substances 0.000 description 35
- 238000003786 synthesis reaction Methods 0.000 description 34
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 33
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 30
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 30
- 238000006243 chemical reaction Methods 0.000 description 30
- 239000002904 solvent Substances 0.000 description 30
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 26
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- 238000003756 stirring Methods 0.000 description 23
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 23
- SLCVBVWXLSEKPL-UHFFFAOYSA-N neopentyl glycol Chemical compound OCC(C)(C)CO SLCVBVWXLSEKPL-UHFFFAOYSA-N 0.000 description 21
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- 229920000642 polymer Polymers 0.000 description 18
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 16
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 15
- 125000001424 substituent group Chemical group 0.000 description 15
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 15
- 150000001543 aryl boronic acids Chemical class 0.000 description 14
- 238000000034 method Methods 0.000 description 14
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 13
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- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 10
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- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 8
- ZADPBFCGQRWHPN-UHFFFAOYSA-N boronic acid Chemical compound OBO ZADPBFCGQRWHPN-UHFFFAOYSA-N 0.000 description 8
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 8
- 229910052794 bromium Inorganic materials 0.000 description 8
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- HXITXNWTGFUOAU-UHFFFAOYSA-N phenylboronic acid Chemical compound OB(O)C1=CC=CC=C1 HXITXNWTGFUOAU-UHFFFAOYSA-N 0.000 description 8
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Classifications
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- 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
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Obesity (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Hematology (AREA)
- Diabetes (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (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 (4)
| 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 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2275888T3 true ES2275888T3 (es) | 2007-06-16 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES02746808T Expired - Lifetime ES2275888T3 (es) | 2001-06-29 | 2002-07-01 | Acidos aril-boronicos para el tratamiento de la obesidad. |
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| CA (1) | CA2489681A1 (cg-RX-API-DMAC7.html) |
| CY (1) | CY1105829T1 (cg-RX-API-DMAC7.html) |
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| PT (1) | PT1404685E (cg-RX-API-DMAC7.html) |
| WO (1) | WO2003002570A1 (cg-RX-API-DMAC7.html) |
Families Citing this family (25)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6858592B2 (en) * | 2001-06-29 | 2005-02-22 | Genzyme Corporation | Aryl boronic acids for treating obesity |
| US7041280B2 (en) * | 2001-06-29 | 2006-05-09 | Genzyme Corporation | Aryl boronate functionalized polymers for treating obesity |
| AU2003223930A1 (en) * | 2002-06-14 | 2003-12-31 | 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 |
| AU2005304318A1 (en) * | 2004-11-12 | 2006-05-18 | Trustees Of Tufts College | Lipase inhibitors |
| US7696347B2 (en) * | 2005-03-14 | 2010-04-13 | Eisai R&D Management Co., Ltd. | Oxymethyl boron compounds |
| 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 |
| WO2009012596A1 (en) * | 2007-07-24 | 2009-01-29 | The University Of British Columbia | Substituted aryl-fluoroborates as imaging agents |
| AU2009233711B2 (en) * | 2008-04-09 | 2015-02-12 | 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 |
| WO2010118159A1 (en) | 2009-04-07 | 2010-10-14 | Infinity Pharmaceuticals, Inc. | Inhibitors of fatty acid amide hydrolase |
| 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 |
| WO2014021845A1 (en) * | 2012-07-31 | 2014-02-06 | Empire Technology Development Llc | Polymerizable organoboron alkyd resin anti fouling coatings |
| WO2014062794A1 (en) * | 2012-10-17 | 2014-04-24 | Board Of Supervisors Of Louisiana State University And Agricultural And Mechanical College | Compositions and methods for improving glucose uptake |
| CA2903281C (en) | 2013-03-08 | 2022-11-29 | The University Of British Columbia | Substituted organofluoroborates as imaging agents |
| EP3913068B1 (en) | 2015-10-12 | 2023-08-02 | 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 |
| CA3118223A1 (en) | 2018-12-18 | 2020-06-25 | Provincial Health Services Authority | Dual mode 18f-labelled theranostic compounds and uses thereof |
| WO2022082312A1 (en) | 2020-10-21 | 2022-04-28 | Provincial Health Services Authority | Novel cxcr4-targeting compounds |
| EP4313033A4 (en) * | 2021-03-24 | 2025-04-23 | 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 |
| EP0674635B1 (en) | 1992-12-21 | 2001-03-28 | Syngenta Limited | Quinuclidine derivatives as squalene synthase inhibitors |
| GB2276162A (en) | 1993-03-17 | 1994-09-21 | Glaxo Group Ltd | Aniline and benazilide derivatives |
| JP3894949B2 (ja) | 1993-06-30 | 2007-03-22 | ザ、ウェルカム、ファンデーション、リミテッド | 抗アテローム性動脈硬化症ジアリール化合物 |
| BR9407048A (pt) | 1993-07-09 | 1996-08-13 | Novo Nordisk As | Composiçao liquida |
| 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 |
| CZ220296A3 (en) | 1994-01-27 | 1996-10-16 | Ciba Geigy Ag | Process for preparing derivatives of arylacetic acid esters and intermediates employed in the process |
| 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. |
| JPH11505509A (ja) | 1994-12-09 | 1999-05-21 | スミスクライン・ビーチャム・コーポレイション | 二環式フィブリノーゲン拮抗薬 |
| JPH10511855A (ja) | 1995-01-09 | 1998-11-17 | ノボ ノルディスク アクティーゼルスカブ | 液体酵素組成物の安定化 |
| DE69608551T2 (de) | 1995-03-27 | 2001-01-18 | Smithkline Beecham P.L.C., Brentford | Bicyclische amin-derivate und ihre verwendung als antipsychotische wirkstoffe |
| UA58494C2 (uk) | 1995-06-07 | 2003-08-15 | Зенека Лімітед | Похідні n-гетероарилпіридинсульфонаміду, фармацевтична композиція, спосіб одержання та спосіб протидії впливам ендотеліну |
| JP3895377B2 (ja) | 1995-06-13 | 2007-03-22 | ノボザイムス アクティーゼルスカブ | 酵素安定剤としての４−置換フェニルボロン酸 |
| 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 |
| WO1998022820A1 (en) | 1996-11-21 | 1998-05-28 | Lawrence Livermore National Laboratory | Detection of biological molecules using boronate-based chemical amplification and optical sensors |
| US6159979A (en) | 1997-04-18 | 2000-12-12 | Smithkline Beecham P.L.C. | Bicyclic aryl or a bicyclic heterocyclic ring containing compounds having a combined 5HT1A, 5HT1B and 5HT1D receptor antagonistic activity |
| US6075014A (en) | 1997-06-13 | 2000-06-13 | Northwestern University | Inhibitors of β-lactamases and uses therefor |
| US6184363B1 (en) | 1997-06-13 | 2001-02-06 | Northwestern University | Inhibitors of β-lactamases and uses therefor |
| US6239138B1 (en) | 1997-07-25 | 2001-05-29 | Smithkline Beecham Corporation | Vitronectin receptor antagonist |
| 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 |
| ES2183532T3 (es) | 1998-03-18 | 2003-03-16 | Ciba Sc Holding Ag | Reacciones de copulacion con catalizadores de paladio. |
| US6525099B1 (en) | 1998-07-31 | 2003-02-25 | Eli Lilly And Company | N-substituted sulfonamide derivatives |
| WO2000014083A1 (en) | 1998-09-09 | 2000-03-16 | Inflazyme Pharmaceuticals Ltd. | SUBSTITUTED η-PHENYL-Δ-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 |
| AU3124300A (en) | 1998-12-16 | 2000-07-03 | Northwestern University | Inhibitors of beta-lactamases and uses therefor |
| EP1147214B1 (en) | 1999-01-13 | 2011-01-05 | The Research Foundation Of State University Of New York | A novel method for designing protein kinase inhibitors |
| WO2000061571A1 (en) | 1999-04-14 | 2000-10-19 | Pacific Corporation | 4,5-diaryl-3(2h)-furanone derivatives as cyclooxygenase-2 inhibitors |
| 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 |
| EP1881050B1 (en) | 2000-11-30 | 2013-01-09 | Canon Kabushiki Kaisha | Luminescence device and display apparatus |
| 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 |
| AU2003243594A1 (en) | 2002-06-13 | 2003-12-31 | 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 AU AU2002316499A patent/AU2002316499B2/en not_active Ceased
- 2002-07-01 EP EP02746808A patent/EP1404685B1/en not_active Expired - Lifetime
- 2002-07-01 WO PCT/US2002/020923 patent/WO2003002570A1/en not_active Ceased
- 2002-07-01 AT AT02746808T patent/ATE339426T1/de not_active IP Right Cessation
- 2002-07-01 PT PT02746808T patent/PT1404685E/pt unknown
- 2002-07-01 DK DK02746808T patent/DK1404685T3/da active
- 2002-07-01 ES ES02746808T patent/ES2275888T3/es not_active Expired - Lifetime
- 2002-07-01 CA CA002489681A patent/CA2489681A1/en not_active Abandoned
- 2002-07-01 JP JP2003508951A patent/JP2004535452A/ja active Pending
- 2002-07-01 DE DE60214713T patent/DE60214713T2/de not_active Expired - Fee Related
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2004
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- 2006-12-05 CY CY20061101748T patent/CY1105829T1/el unknown
Also Published As
| Publication number | Publication date |
|---|---|
| US20050107336A1 (en) | 2005-05-19 |
| WO2003002570A1 (en) | 2003-01-09 |
| CA2489681A1 (en) | 2003-01-09 |
| US6858592B2 (en) | 2005-02-22 |
| EP1404685A1 (en) | 2004-04-07 |
| DE60214713D1 (de) | 2006-10-26 |
| US20060128664A1 (en) | 2006-06-15 |
| DE60214713T2 (de) | 2007-09-06 |
| HK1065046A1 (en) | 2005-02-08 |
| US7049304B2 (en) | 2006-05-23 |
| CY1105829T1 (el) | 2011-02-02 |
| ATE339426T1 (de) | 2006-10-15 |
| AU2005220192A1 (en) | 2005-12-01 |
| EP1404685B1 (en) | 2006-09-13 |
| AU2002316499B2 (en) | 2005-08-04 |
| US20030064963A1 (en) | 2003-04-03 |
| DK1404685T3 (da) | 2007-01-22 |
| JP2004535452A (ja) | 2004-11-25 |
| PT1404685E (pt) | 2007-01-31 |
| US7456156B2 (en) | 2008-11-25 |
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