ES2291196T3 - Uso de complejos de epoxido hidrolasas para tratar la hipertension. - Google Patents
Uso de complejos de epoxido hidrolasas para tratar la hipertension. Download PDFInfo
- Publication number
- ES2291196T3 ES2291196T3 ES00911767T ES00911767T ES2291196T3 ES 2291196 T3 ES2291196 T3 ES 2291196T3 ES 00911767 T ES00911767 T ES 00911767T ES 00911767 T ES00911767 T ES 00911767T ES 2291196 T3 ES2291196 T3 ES 2291196T3
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- Spain
- Prior art keywords
- epoxide
- hydrolase
- compounds
- compound
- hydrogen
- 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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| US252148 | 1999-02-18 | ||
| US09/252,148 US6150415A (en) | 1996-08-13 | 1999-02-18 | Epoxide hydrolase complexes and methods therewith |
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| ES2291196T3 true ES2291196T3 (es) | 2008-03-01 |
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| ES00911767T Expired - Lifetime ES2291196T3 (es) | 1999-02-18 | 2000-02-10 | Uso de complejos de epoxido hidrolasas para tratar la hipertension. |
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| ES (1) | ES2291196T3 (enExample) |
| WO (1) | WO2000048593A1 (enExample) |
Families Citing this family (65)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6150415A (en) * | 1996-08-13 | 2000-11-21 | The Regents Of The University Of California | Epoxide hydrolase complexes and methods therewith |
| US8815951B2 (en) * | 1996-08-13 | 2014-08-26 | The Regents Of The University Of California | Inhibitors of epoxide hydrolases for the treatment of inflammation |
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| EP1140840B1 (en) | 1999-01-13 | 2006-03-22 | Bayer Pharmaceuticals Corp. | -g(v)-carboxyaryl substituted diphenyl ureas as raf kinase inhibitors |
| US6831099B1 (en) * | 1999-05-12 | 2004-12-14 | Yale University | Enzyme inhibition |
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| US6562563B1 (en) | 1999-11-03 | 2003-05-13 | Mitokor | Compositions and mehtods for determining interactions of mitochondrial components, and for identifying agents that alter such interactions |
| US7235576B1 (en) | 2001-01-12 | 2007-06-26 | Bayer Pharmaceuticals Corporation | Omega-carboxyaryl substituted diphenyl ureas as raf kinase inhibitors |
| US6794158B2 (en) * | 2001-04-09 | 2004-09-21 | Boehringer Ingelheim Pharmaceuticals, Inc. | Fluorescence polarization assay |
| US7371763B2 (en) | 2001-04-20 | 2008-05-13 | Bayer Pharmaceuticals Corporation | Inhibition of raf kinase using quinolyl, isoquinolyl or pyridyl ureas |
| US6756210B2 (en) * | 2001-05-29 | 2004-06-29 | The Regents Of The University Of California | Linoleic acid diol and glucuronide conjugate levels as diagnostic markers of disorders of abnormal regulation of cytochrome P450 metabolism of unsaturated fatty acids |
| EP1578987A2 (en) * | 2001-08-03 | 2005-09-28 | Diversa Corporation | Epoxide hydrolases, nucleic acids encoding them and methods for making and using them |
| US6943001B2 (en) * | 2001-08-03 | 2005-09-13 | Diversa Corporation | Epoxide hydrolases, nucleic acids encoding them and methods for making and using them |
| US20030139469A1 (en) * | 2002-01-23 | 2003-07-24 | The Regents Of The University Of California | Use of inhibitors of soluble epoxide hydrolase to inhibit vascular smooth muscle cell proliferation |
| AU2003209119A1 (en) | 2002-02-11 | 2003-09-04 | Bayer Pharmaceuticals Corporation | Pyridine, quinoline, and isoquinoline n-oxides as kinase inhibitors |
| ES2425739T3 (es) | 2002-02-11 | 2013-10-17 | Bayer Healthcare Llc | Sorafenib-tosilato para el tratamiento de enfermedades caracterizadas por angiogénesis anormal |
| CA2475818C (en) | 2002-02-11 | 2011-07-19 | Bayer Pharmaceuticals Corporation | Aryl ureas as kinase inhibitors |
| GB0214342D0 (en) * | 2002-06-21 | 2002-07-31 | Givaudan Sa | Insect repellents |
| UA80841C2 (en) | 2002-10-07 | 2007-11-12 | Univ California | Fatty acid amide hydrolase inhibitors, pharmaceutical composition (variants) and method to treat appetite disorders, glaucoma, pain, and related neurological disorders (variants) |
| US7557129B2 (en) | 2003-02-28 | 2009-07-07 | Bayer Healthcare Llc | Cyanopyridine derivatives useful in the treatment of cancer and other disorders |
| US20050164951A1 (en) * | 2003-04-03 | 2005-07-28 | The Regents Of The University Of California | Inhibitors for the soluble epoxide hydrolase |
| WO2004089296A2 (en) | 2003-04-03 | 2004-10-21 | The Regents Of The University Of California | Improved inhibitors for the soluble epoxide hydrolase |
| DE602004011340T2 (de) | 2003-05-20 | 2008-11-06 | Bayer Healthcare Llc | Diaryl-harnstoffe mit kinasehemmender wirkung |
| NZ544920A (en) | 2003-07-23 | 2009-11-27 | Bayer Healthcare Llc | 4{4-[3-(4-chloro-3-trifluoromethylphenyl)-ureido]-3-fluorophenoxy}-pyridine-2-carboxylic acid methylamide and metabolites for the treatment and prevention of diseases and conditions |
| CA2559665A1 (en) | 2004-03-16 | 2005-09-29 | The Regents Of The University Of California | Reducing nephropathy with inhibitors of soluble epoxide hydrolase and epoxyeicosanoids |
| ES2257152B1 (es) * | 2004-05-31 | 2007-07-01 | Laboratorios Almirall S.A. | Combinaciones que comprenden agentes antimuscarinicos y agonistas beta-adrenergicos. |
| NZ554555A (en) * | 2004-10-20 | 2011-09-30 | Univ California | Cyclohexyl-urea derivatives as improved inhibitors for the soluble epoxide hydrolase |
| JP2008540424A (ja) * | 2005-05-06 | 2008-11-20 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | ｓＥＨインヒビターとしてのアシルヒドラゾンの使用方法 |
| JP2008540433A (ja) * | 2005-05-06 | 2008-11-20 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | 可溶性エポキシドヒドロラーゼインヒビター及びその使用方法 |
| EP1931201B1 (en) * | 2005-08-19 | 2012-05-02 | The Regents of the University of California | Use of seh inhibitors as analgesics |
| CA2622754A1 (en) * | 2005-10-07 | 2007-04-19 | Boehringer Ingelheim International Gmbh | N-substituted pyridinone or pyrimidinone compounds useful as soluble epoxide hydrolase inhibitors |
| ES2415756T3 (es) | 2005-11-09 | 2013-07-26 | Onyx Therapeutics, Inc. | Compuestos para la inhibición de enzimas |
| EP1973868B1 (en) * | 2006-01-13 | 2015-09-09 | McGill University | Novel elatonin ligands having antidepressant activity as well as sleep inducing properties |
| JP2009529577A (ja) * | 2006-03-10 | 2009-08-20 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | 可溶性エポキシドヒドロラーゼインヒビター及びその使用方法 |
| AR059826A1 (es) * | 2006-03-13 | 2008-04-30 | Univ California | Inhibidores de urea conformacionalmente restringidos de epoxido hidrolasa soluble |
| ES2415632T3 (es) | 2006-06-19 | 2013-07-26 | Onyx Therapeutics, Inc. | Epoxicetonas peptídicas para la inhibición del proteosoma |
| WO2008073130A1 (en) * | 2006-12-15 | 2008-06-19 | Regents Of The University Of California | Use of cis-epoxyeicosatrienoic acids and inhibitors of soluble epoxide hydrolase to treat conditions mediated by pbr, cb2, and nk2 receptors |
| JP2010513372A (ja) * | 2006-12-18 | 2010-04-30 | エフ．ホフマン−ラ ロシュ アーゲー | 可溶性エポキシドヒドロラーゼの阻害剤の新規な使用 |
| WO2009011872A1 (en) * | 2007-07-17 | 2009-01-22 | Merck & Co., Inc. | Soluble epoxide hydrolase inhibitors, compositions containing such compounds and methods of treatment |
| EP2187746A4 (en) * | 2007-08-06 | 2011-01-19 | Univ California | PREPARATION OF NEW 1,3-SUBSTITUTED UREASES AS A HOLDER OF SOLUBLE EPOXY HYDROLASE |
| EP2207791B2 (en) | 2007-10-04 | 2019-08-07 | Onyx Therapeutics, Inc. | Crystalline peptide epoxy ketone protease inhibitors and the synthesis of amino acid keto-epoxides |
| WO2009111207A1 (en) * | 2008-03-04 | 2009-09-11 | Merck & Co., Inc. | Soluble epoxide hydrolase inhibitors, compositions containing such compounds and methods of treatment |
| EP2100598A1 (en) | 2008-03-13 | 2009-09-16 | Laboratorios Almirall, S.A. | Inhalation composition containing aclidinium for treatment of asthma and chronic obstructive pulmonary disease |
| EP2100599A1 (en) | 2008-03-13 | 2009-09-16 | Laboratorios Almirall, S.A. | Inhalation composition containing aclidinium for treatment of asthma and chronic obstructive pulmonary disease |
| EA024364B1 (ru) | 2008-10-21 | 2016-09-30 | Оникс Терапьютикс, Инк. | Способ лечения множественной миеломы |
| WO2010096722A1 (en) | 2009-02-20 | 2010-08-26 | Takeda Pharmaceutical Company Limited | 3-oxo-2, 3-dihydro- [1,2, 4] triazolo [4, 3-a]pyridines as soluble epoxide hydrolase (seh) inhibitors |
| TWI504598B (zh) | 2009-03-20 | 2015-10-21 | Onyx Therapeutics Inc | 結晶性三肽環氧酮蛋白酶抑制劑 |
| WO2011060179A1 (en) | 2009-11-13 | 2011-05-19 | Onyx Therapeutics, Inc | Use of peptide epoxyketones for metastasis suppression |
| WO2012054093A2 (en) | 2010-01-29 | 2012-04-26 | The Regents Of The University Of California | Acyl piperidine inhibitors of soluble epoxide hydrolase |
| EP2542238B1 (en) | 2010-03-01 | 2015-08-12 | Onyx Therapeutics, Inc. | Compounds for immunoproteasome inhibition |
| BR112012025264A2 (pt) | 2010-04-07 | 2019-09-24 | Onyx Therapeutics Inc | inibidor de imunoproteassoma de e´poxicetona peptídica cristalina. |
| EP2389922A1 (en) | 2010-05-25 | 2011-11-30 | Symrise AG | Cyclohexyl carbamate compounds as anti-ageing actives |
| CA2826277A1 (en) | 2011-02-14 | 2012-08-23 | The Regents Of The University Of California | Sorafenib derivatives as seh inhibitors |
| EP2510928A1 (en) | 2011-04-15 | 2012-10-17 | Almirall, S.A. | Aclidinium for use in improving the quality of sleep in respiratory patients |
| CN104093708B (zh) | 2012-02-01 | 2016-11-09 | 加利福尼亚大学董事会 | 可溶性环氧化物水解酶的酰基哌啶抑制剂 |
| WO2013138118A1 (en) | 2012-03-14 | 2013-09-19 | The Regents Of The University Of California | Treatment of inflammatory disorders in non-human mammals |
| UY34897A (es) | 2012-07-09 | 2014-01-31 | Onyx Therapeutics Inc | Profarmacos de inhibidores peptidicos de expoxi cetona proteasa |
| US10813894B2 (en) | 2015-02-20 | 2020-10-27 | The Regents Of The University Of California | Methods of inhibiting pain |
| US20200317813A1 (en) | 2016-05-25 | 2020-10-08 | Johann Wolfgang Goethe-Universitat Frankfurt Am Main | Treatment and diagnosis of non-proliferative diabetic retinopathy |
| US20210378995A1 (en) | 2018-10-10 | 2021-12-09 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods and topical pharmaceutical compositions for the treatment of skin microvascular dysfunction |
| WO2020097588A1 (en) | 2018-11-09 | 2020-05-14 | Ginkgo Bioworks, Inc. | Biosynthesis of mogrosides |
Family Cites Families (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1056290A (en) * | 1963-05-06 | 1967-01-25 | Du Pont | Dicycloalkyl ureas |
| CA2017383A1 (en) * | 1989-06-08 | 1990-12-08 | Raymond R. Martodam | Use of vanilloids for the treatment of respiratory diseases or disorders |
| CA2036770C (en) * | 1990-02-26 | 2003-09-09 | Jeffrey P. Whitten | Inhibitors of nitric oxide biosynthesis |
| US5445956A (en) * | 1993-08-13 | 1995-08-29 | The Regents Of The University Of California | Recombinant soluble epoxide hydrolase |
| US5599984A (en) * | 1994-01-21 | 1997-02-04 | The Picower Institute For Medical Research | Guanylhydrazones and their use to treat inflammatory conditions |
| JP2909620B2 (ja) * | 1995-03-07 | 1999-06-23 | 参天製薬株式会社 | Ｎ，ｎ−ジアルキルアミノフェニル基を有する新規アミノ酸誘導体 |
| US6150415A (en) * | 1996-08-13 | 2000-11-21 | The Regents Of The University Of California | Epoxide hydrolase complexes and methods therewith |
| US5955496A (en) * | 1996-08-13 | 1999-09-21 | The Regents Of The University Of California | Dihydroxy-oxy-eicosadienoates |
-
1999
- 1999-02-18 US US09/252,148 patent/US6150415A/en not_active Expired - Lifetime
-
2000
- 2000-02-10 JP JP2000599385A patent/JP2002540767A/ja active Pending
- 2000-02-10 DK DK00911767T patent/DK1154764T3/da active
- 2000-02-10 DE DE60036690T patent/DE60036690T2/de not_active Expired - Lifetime
- 2000-02-10 EP EP00911767A patent/EP1154764B1/en not_active Expired - Lifetime
- 2000-02-10 AU AU33608/00A patent/AU3360800A/en not_active Abandoned
- 2000-02-10 ES ES00911767T patent/ES2291196T3/es not_active Expired - Lifetime
- 2000-02-10 AT AT00911767T patent/ATE375153T1/de active
- 2000-02-10 CA CA2362331A patent/CA2362331C/en not_active Expired - Fee Related
- 2000-02-10 WO PCT/US2000/003495 patent/WO2000048593A1/en not_active Ceased
- 2000-02-10 EP EP07014966A patent/EP1844767B1/en not_active Expired - Lifetime
Also Published As
| Publication number | Publication date |
|---|---|
| CA2362331C (en) | 2010-04-20 |
| DE60036690T2 (de) | 2008-07-17 |
| WO2000048593A1 (en) | 2000-08-24 |
| DE60036690D1 (de) | 2007-11-22 |
| JP2002540767A (ja) | 2002-12-03 |
| EP1154764A4 (en) | 2005-02-16 |
| DK1154764T3 (da) | 2008-02-04 |
| AU3360800A (en) | 2000-09-04 |
| EP1154764B1 (en) | 2007-10-10 |
| CA2362331A1 (en) | 2000-08-24 |
| ATE375153T1 (de) | 2007-10-15 |
| US6150415A (en) | 2000-11-21 |
| EP1154764A1 (en) | 2001-11-21 |
| EP1844767B1 (en) | 2012-08-29 |
| EP1844767A3 (en) | 2010-01-13 |
| EP1844767A2 (en) | 2007-10-17 |
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