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1. 发明申请

US20050282767A1 Inhibitors of epoxide hydrolases for the treatment of hypertension 审中-公开
标题翻译：环氧化物水解酶抑制剂治疗高血压
公开(公告)号：US20050282767A1
公开(公告)日：2005-12-22
申请号：US11189964
申请日：2005-07-25
申请人： Deanna Kroetz , Darryl Zeldin , Bruce Hammock , Christophe Morisseau
发明人： Deanna Kroetz , Darryl Zeldin , Bruce Hammock , Christophe Morisseau
IPC分类号： A61K31/00 , A61K31/325 , A61K31/336 , A61K48/00
CPC分类号： A61K31/325 , A61K31/00 , A61K31/336
摘要： The invention provides compounds that inhibit epoxide hydrolase in therapeutic applications for treating hypertension. A preferred class of compounds for practicing the invention have the structure shown by Formula I wherein Z is oxygen or sulfur, W is carbon phosphorous or sulfur, X and Y is each independently nitrogen, oxygen, or sulfur, and X can further be carbon, at least one of R1—R4 is hydrogen, R2 is hydrogen when X is nitrogen but is not present when X is sulfur or oxygen, R4 is hydrogen when Y is nitrogen but is not present when Y is sulfur or oxygen, R1 and R3 is each independently C1-C20 substituted or unsubstituted alkyl, cycloalkyl, aryl, acyl, or heterocyclic.
摘要翻译：本发明提供在治疗高血压的治疗应用中抑制环氧化物水解酶的化合物。用于实施本发明的优选类化合物具有式I所示的结构，其中Z是氧或硫，W是碳磷或硫，X和Y各自独立地是氮，氧或硫，并且X还可以是碳， R 1至R 4中的至少一个为氢，当X为氮时，R 2为氢，但当X为硫或不存在时不存在当Y为氮时，氧，R 4为氢，但当Y为硫或氧时不存在，R 1和R 3各自独立地为 C 1 -C 20取代或未取代的烷基，环烷基，芳基，酰基或杂环。

2. 发明授权

US08409821B2 Detection of hypertension using glucuronidated metabolic products 有权
标题翻译：使用葡萄糖醛酸化代谢产物检测高血压
公开(公告)号：US08409821B2
公开(公告)日：2013-04-02
申请号：US12716570
申请日：2010-03-03
申请人： Hyesook Kim , Jorge H. Capdevila , Raymond F. Novak , Deanna Kroetz
发明人： Hyesook Kim , Jorge H. Capdevila , Raymond F. Novak , Deanna Kroetz
IPC分类号： G01N33/53 , G01N33/531 , G01N33/532 , C12Q1/48 , C07K16/00
CPC分类号： G01N33/88 , G01N2800/321
摘要： A method of assessing arachidonic acid (AA) metabolites-dependent hypertension by measuring glucuronidated dihydroxyeicosatrienoic acids (DHETs) and DHET metabolites in a biological sample which contains the epitopes unique to DHET (using any methods including GC/MS, LC/MS or ELISA). An example of the glucuronidated DHET metabolite is DHET-alcohols such as omega or omega-1 oxidated DHET and DHET esterified glycerol. The method further includes determining the amount of glucuronidated molecules containing a DHET-specific epitope which is immunoreactive with antibodies produced against DHETs.
摘要翻译：通过测量包含DHET特有的表位的生物样品中的葡糖苷酸化二羟基二十碳三烯酸（DHET）和DHET代谢物来评估花生四烯酸（AA）代谢物依赖性高血压的方法（使用任何方法，包括GC / MS，LC / MS或ELISA）。葡萄糖醛酸化的DHET代谢物的实例是DHET-醇，例如ω或ω-1氧化的DHET和DHET酯化甘油。该方法还包括确定含有针对DHET产生的抗体具有免疫反应性的DHET特异性表位的葡糖醛酸化分子的量。

3. 发明授权

US07695927B2 Detection of hypertension using glucuronidated metabolic products 有权
标题翻译：使用葡萄糖醛酸化代谢产物检测高血压
公开(公告)号：US07695927B2
公开(公告)日：2010-04-13
申请号：US11378062
申请日：2006-03-17
申请人： Hyesook Kim , Jorge H. Capdevila , Raymond R. Novak , Deanna Kroetz
发明人： Hyesook Kim , Jorge H. Capdevila , Raymond R. Novak , Deanna Kroetz
IPC分类号： G01N33/53 , G01N33/531 , C12Q1/48 , G01N33/532 , C07K16/00
CPC分类号： G01N33/88 , G01N2800/321
摘要： A method to assess arachidonic acid (AA) metabolites-dependent hypertension by measuring glucuronidated dihydroxyeicosatrienoic acids (DHETs) and DHET metabolites in a biological sample which contains the epitopes unique to DHET (using any methods including GC/MS, LC/MS or ELISA) is disclosed. An example of the glucuronidated DHET metabolite is DHET-alcohols such as omega or omega-1 oxidated DHET and DHET esterified glycerol. The method further includes determining the amount of glucuronidated molecules containing a DHET-specific epitope which is immunoreactive with antibodies produced against DHETs. The present invention measuring glucuronidated DHET levels in a biological sample is useful for drug development and monitoring efficiency of drug treatment of a mammal who has AA epoxygenase-, epoxide hydrolase-and/or UDP-glucuronosyl transferase-dependent hypertension.
摘要翻译：通过测量包含DHET特有的表位的生物样品中的葡糖醛酸二羟基二十碳三烯酸（DHET）和DHET代谢物来评估花生四烯酸（AA）代谢物依赖性高血压的方法（使用任何方法，包括GC / MS，LC / MS或ELISA）被披露。葡萄糖醛酸化的DHET代谢物的实例是DHET-醇，例如ω或ω-1氧化的DHET和DHET酯化甘油。该方法还包括确定含有针对DHET产生的抗体具有免疫反应性的DHET特异性表位的葡糖醛酸化分子的量。测量生物样品中葡萄糖醛酸化的DHET水平的本发明可用于具有AA环氧化酶，环氧化物水解酶和/或UDP-葡萄糖醛酸转移酶依赖性高血压的哺乳动物的药物治疗的药物开发和监测效率。

4. 发明授权

US06534282B2 Detection of hypertension using immunoreactive metabolic products 有权
公开(公告)号：US06534282B2
公开(公告)日：2003-03-18
申请号：US09946644
申请日：2001-09-04
申请人： Hyesook Kim , Jorge H. Capdevila , Raymond R. Novak , Deanna Kroetz
发明人： Hyesook Kim , Jorge H. Capdevila , Raymond R. Novak , Deanna Kroetz
IPC分类号： G01N3353
CPC分类号： C12Q1/26 , C12Q1/34 , G01N33/88 , Y10S435/973 , Y10S436/808 , Y10S436/811 , Y10S436/815 , Y10T436/25 , Y10T436/25875
摘要： A method to assess hypertension by measuring the amount of free and conjugated hydroxyeicosatrienoic acids (DHETs) and metabolites of DHETs, which are metabolites of arachidonic acid (AA) epoxygenases and epoxide hydrolases, in a biological sample which contains the DHETs (using any methods including GC/MS or ELISA) is disclosed. The method further included determining the amount of molecules containing a DHET-specific epitope immunoreactive with antibodies produced against DHETs present in the sample. This amount is compared with a control sample(s). Hypertension is determined through the comparison wherein the amount of increase of free and conjugated DHETs and metabolites of DHETs in the sample isolated from an organism. The present invention also provides a method to assess catalytic activity of AA epoxygenases using immunoassays by subtracting the amounts of NADPH-independent epoxyeicosatriencic acids (EETs) from total (NADPH-dependent+independent) EETs. The present invention also provides a method to decrease hepatic M epoxygenase expression including 2C23 by treatment of rats with a glucocorticoid including dexamethasone.

5. 发明申请

US20100159481A1 DETECTION OF HYPERTENSION USING GLUCURONIDATED METABOLIC PRODUCTS 有权
标题翻译：使用GLUCURONIDATED代谢产物检测高血压
公开(公告)号：US20100159481A1
公开(公告)日：2010-06-24
申请号：US12716570
申请日：2010-03-03
申请人： Hyesook Kim , Jorge H. Capdevila , Raymond F. Novak , Deanna Kroetz
发明人： Hyesook Kim , Jorge H. Capdevila , Raymond F. Novak , Deanna Kroetz
IPC分类号： G01N33/573 , C12Q1/34
CPC分类号： G01N33/88 , G01N2800/321
摘要： A method of assessing arachidonic acid (AA) metabolites-dependent hypertension by measuring glucuronidated dihydroxyeicosatrienoic acids (DHETs) and DHET metabolites in a biological sample which contains the epitopes unique to DHET (using any methods including GC/MS, LC/MS or ELISA). An example of the glucuronidated DHET metabolite is DHET-alcohols such as omega or omega-1 oxidated DHET and DHET esterified glycerol. The method further includes determining the amount of glucuronidated molecules containing a DHET-specific epitope which is immunoreactive with antibodies produced against DHETs.
摘要翻译：通过测量包含DHET特有的表位的生物样品中的葡糖醛酸二羟基二十碳三烯酸（DHET）和DHET代谢物来评估花生四烯酸（AA）代谢物依赖性高血压的方法（使用任何方法，包括GC / MS，LC / MS或ELISA）。葡萄糖醛酸化的DHET代谢物的一个实例是DHET-醇如ω或ω-1氧化的DHET和DHET酯化甘油。该方法还包括确定含有针对DHET产生的抗体具有免疫反应性的DHET特异性表位的葡糖醛酸化分子的量。

6. 发明申请

US20060211064A1 Detection of hypertension using glucuronidated metabolic products 有权
标题翻译：使用葡萄糖醛酸化代谢产物检测高血压
公开(公告)号：US20060211064A1
公开(公告)日：2006-09-21
申请号：US11378062
申请日：2006-03-17
申请人： Hyesook Kim , Jorge Capdevila , Raymond Novak , Deanna Kroetz
发明人： Hyesook Kim , Jorge Capdevila , Raymond Novak , Deanna Kroetz
IPC分类号： G01N33/92 , G01N33/53
CPC分类号： G01N33/88 , G01N2800/321
摘要： A method of assessing arachidonic acid (AA) metabolites-dependent hypertension by measuring glucuronidated dihydroxyeicosatrienoic acids (DHETS) and DHET metabolites in a biological sample which contains the epitopes unique to DHET (using any methods including GC/MS, LC/MS or ELISA). An example of the glucuronidated DHET metabolite is DHET-alcohols such as omega or omega-1 oxidated DHET and DHET esterified glycerol. The method further includes determining the amount of glucuronidated molecules containing a DHET-specific epitope which is immunoreactive with antibodies produced against DHETs.
摘要翻译：通过测量包含DHET特有的表位的生物样品中的葡糖苷酸化二羟基二十碳三烯酸（DHETS）和DHET代谢物来评估花生四烯酸（AA）代谢物依赖性高血压的方法（使用任何方法，包括GC / MS，LC / MS或ELISA）。葡萄糖醛酸化的DHET代谢物的实例是DHET-醇，例如ω或ω-1氧化的DHET和DHET酯化甘油。该方法还包括确定含有针对DHET产生的抗体具有免疫反应性的DHET特异性表位的葡糖醛酸化分子的量。

7. 发明授权

US06440682B1 Detection of hypertension using immunoreactive metabolic products 有权
标题翻译：使用免疫反应性代谢产物检测高血压
公开(公告)号：US06440682B1
公开(公告)日：2002-08-27
申请号：US09578821
申请日：2000-05-24
申请人： Hyesook Kim , Jorge H. Capdevila , Raymond R. Novak , Deanna Kroetz
发明人： Hyesook Kim , Jorge H. Capdevila , Raymond R. Novak , Deanna Kroetz
IPC分类号： G01N3353
CPC分类号： C12Q1/26 , C12Q1/34 , G01N33/88 , Y10S435/973 , Y10S436/808 , Y10S436/811 , Y10S436/815 , Y10T436/25 , Y10T436/25875
摘要： A method to assess hypertension by measuring the amount of free and conjugated hydroxyeicosatrienoic acids (DHETS) and metabolites of DHETs, which are metabolites of arachidonic acid (AA) epoxygenases and epoxide hydrolases, in a biological sample which contains the DHETs (using any methods including GC/MS or ELISA) is disclosed. The method further included determining the amount of molecules containing a DHET-specific epitope immunoreactive with antibodies produced against DHETs present in the sample. This amount is compared with a control sample(s). Hypertension is determined through the comparison wherein the amount of increase of free and conjugated DHETs and metabolites of DHETs in the sample isolated from an organism. The present invention also provides a method to assess catalytic activity of AA epoxygenases using immunoassays by measuring the amounts of NADPH-independent epoxyeicosatrienoic acids (EETs) and total (NADPH-dependent+independent) EETs. The present invention also provides a method to decrease hepatic AA epoxygenase expression including 2C23 by treatment of rats with a glucocorticoid including dexamethasone.
摘要翻译：通过测量含有DHET的生物样品中的花生四烯酸（AA）环氧化酶和环氧化物水解酶的代谢物的DHET的游离和共轭羟基二十碳烯酸（DHETS）和代谢物的量来评估高血压的方法（使用任何方法，包括 GC / MS或ELISA）。该方法还包括测定含有针对存在于样品中的DHET产生的抗体对与DHET特异性表位免疫反应的分子的量。将该量与对照样品进行比较。通过比较确定高血压，其中分离自生物体的样品中DHET的游离和缀合的DHETs和代谢物的增加量。本发明还提供了通过测量不依赖NADPH的环氧二十碳三烯酸（EET）和总（NADPH依赖+独立）EET的量来免疫测定来评估AA环氧化酶的催化活性的方法。本发明还提供了通过用包括地塞米松在内的糖皮质激素治疗大鼠来减少包括2C23在内的肝AA环氧化酶表达的方法。

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