可溶性环氧化物水解酶(Soluble epoxide hydrolases,sEH)是一种能代谢环氧脂肪酸的酶,它在哺乳动物中广泛存在,能将内源性环氧二十碳三烯酸(Epoxyeicosatrienoic acids or EETs)转化为二羟基二十碳三烯酸(Dihydroxy epoxyeicosatrienoic...可溶性环氧化物水解酶(Soluble epoxide hydrolases,sEH)是一种能代谢环氧脂肪酸的酶,它在哺乳动物中广泛存在,能将内源性环氧二十碳三烯酸(Epoxyeicosatrienoic acids or EETs)转化为二羟基二十碳三烯酸(Dihydroxy epoxyeicosatrienoic acids or DHETs)。内源性EETs是由花生四烯酸(Arachidonic acid or AA)经细胞色素P450氧化而来,它是生物体内重要的信号分子,具有调节离子转运和基因表达、血管扩张、抗炎等作用。在动物体内,有很多种途径可以降解EETs,其中sEH将EETs代谢为DHETs是最主要的代谢途径,使EETs的浓度降低,生理活性下降,从而使体内的血压升高,并进一步影响肾脏,心脏等功能。研究表明,抑制sEH的活性可治疗多种心血管疾病及炎症。因此开发新型sEH的抑制剂在治疗相关疾病中具有很好的应用价值。主要概述了sEH的抑制剂的作用机理以及抑制剂研究的最新进展,并展望了抑制剂今后的研究方向。展开更多
Chlorothalonil 1 was treated with anhydrous KF in DMF at 110 ℃ to give the corresponding crystalline fluorine-containing 1,3-benzenedicarbonitrile 2. KF was used in an equivalent to the number of chlorine atoms to be...Chlorothalonil 1 was treated with anhydrous KF in DMF at 110 ℃ to give the corresponding crystalline fluorine-containing 1,3-benzenedicarbonitrile 2. KF was used in an equivalent to the number of chlorine atoms to be substituted. Compound 2 was subsequently reacted with ammonia to yield compound 3. In addition, halobenzamide 4 were refluxed with oxalyl chloride in anhydrous 1,2-dichloroethane(DCE) to yield benzoylisocyanates 5. Finally, seven novel BPUs chitin inhibitors 6a—6g were synthesized via the selective reaction of compound 3 with benzoylisocyanate derivatives 5, the total yield is over 30%—50%.展开更多
文摘可溶性环氧化物水解酶(Soluble epoxide hydrolases,sEH)是一种能代谢环氧脂肪酸的酶,它在哺乳动物中广泛存在,能将内源性环氧二十碳三烯酸(Epoxyeicosatrienoic acids or EETs)转化为二羟基二十碳三烯酸(Dihydroxy epoxyeicosatrienoic acids or DHETs)。内源性EETs是由花生四烯酸(Arachidonic acid or AA)经细胞色素P450氧化而来,它是生物体内重要的信号分子,具有调节离子转运和基因表达、血管扩张、抗炎等作用。在动物体内,有很多种途径可以降解EETs,其中sEH将EETs代谢为DHETs是最主要的代谢途径,使EETs的浓度降低,生理活性下降,从而使体内的血压升高,并进一步影响肾脏,心脏等功能。研究表明,抑制sEH的活性可治疗多种心血管疾病及炎症。因此开发新型sEH的抑制剂在治疗相关疾病中具有很好的应用价值。主要概述了sEH的抑制剂的作用机理以及抑制剂研究的最新进展,并展望了抑制剂今后的研究方向。
文摘Chlorothalonil 1 was treated with anhydrous KF in DMF at 110 ℃ to give the corresponding crystalline fluorine-containing 1,3-benzenedicarbonitrile 2. KF was used in an equivalent to the number of chlorine atoms to be substituted. Compound 2 was subsequently reacted with ammonia to yield compound 3. In addition, halobenzamide 4 were refluxed with oxalyl chloride in anhydrous 1,2-dichloroethane(DCE) to yield benzoylisocyanates 5. Finally, seven novel BPUs chitin inhibitors 6a—6g were synthesized via the selective reaction of compound 3 with benzoylisocyanate derivatives 5, the total yield is over 30%—50%.
