特定二氢吡啶衍生物对红细胞中钙激活钾通道的特异性抑制作用。
Specific inhibition of Ca-activated K channels in red cells by selected dihydropyridine derivatives.
作者信息
Ellory J C, Culliford S J, Smith P A, Wolowyk M W, Knaus E E
机构信息
Department of Physiology, University of Oxford.
出版信息
Br J Pharmacol. 1994 Mar;111(3):903-5. doi: 10.1111/j.1476-5381.1994.tb14823.x.
Abstract
- Thirty two dihydropyridine derivatives were screened as potential inhibitors of the Ca-activated K-channel in human red cells. 2. Three derivatives (26, 29, 32 see Tables 1 and 2) with high activity were then characterized in detail, and also tested against the smooth muscle Ca-channel and shown to have varying potencies. 3. One of the more potent derivatives (32) and nitrendipine were also tested on the Ca-activated K-channel, Maxi-K channel, from mouse pancreatic beta-cells. 4. We conclude from our results that it may be possible to develop selective Gardos-channel inhibitors based on these molecules, which may be of benefit in the treatment of sickle cell disease.
摘要
- 对32种二氢吡啶衍生物进行了筛选，以确定它们作为人红细胞中钙激活钾通道潜在抑制剂的可能性。2. 然后对三种具有高活性的衍生物（26、29、32，见表1和表2）进行了详细表征，并对平滑肌钙通道进行了测试，结果显示它们具有不同的效力。3. 其中一种活性较强的衍生物（32）和尼群地平也在小鼠胰腺β细胞的钙激活钾通道、大电导钙激活钾通道上进行了测试。4. 我们从结果中得出结论，基于这些分子有可能开发出选择性加尔道斯通道抑制剂，这可能对镰状细胞病的治疗有益。
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本文引用的文献
1
The function of calcium in the potassium permeability of human erythrocytes.钙在人红细胞钾通透性中的作用。
Biochim Biophys Acta. 1958 Dec;30(3):653-4. doi: 10.1016/0006-3002(58)90124-0.
2
Synthesis and calcium channel antagonist activity of dialkyl 1,4-dihydro-2,6-dimethyl-4-(pyridinyl)-3,5-pyridinedicarboxylates.
J Med Chem. 1986 Dec;29(12):2524-9. doi: 10.1021/jm00162a016.
3
Synthesis and calcium channel antagonist activity of dialkyl 4- (dihydropyridinyl)-1,4-dihydro-2,6-dimethyl-3,5-pyridinecarboxylates.4-（二氢吡啶基）-1,4-二氢-2,6-二甲基-3,5-吡啶二甲酸二烷基酯的合成及其钙通道拮抗剂活性
J Med Chem. 1987 Apr;30(4):640-6. doi: 10.1021/jm00387a010.
4
Synthesis and calcium channel antagonist activity of 1,2-dihydropyridyl analogues of nifedipine.硝苯地平的1,2 - 二氢吡啶类似物的合成及钙通道拮抗剂活性
Drug Des Deliv. 1988 Nov;3(3):245-56.
5
6
Varieties of calcium-activated potassium channels.钙激活钾通道的种类。
Annu Rev Physiol. 1989;51:385-99. doi: 10.1146/annurev.ph.51.030189.002125.
7
Synthesis and calcium channel antagonist activity of alkyl cycloalkyl esters of nifedipine containing pyridinyl substituents.
Drug Des Deliv. 1989 Dec;5(2):117-23.
8
Electrophysiology of the pancreatic beta-cell.胰腺β细胞的电生理学
Prog Biophys Mol Biol. 1989;54(2):87-143. doi: 10.1016/0079-6107(89)90013-8.
9
Nifedipine inhibits calcium-activated K transport in human erythrocytes.硝苯地平抑制人红细胞中钙激活的钾转运。
Am J Physiol. 1990 Aug;259(2 Pt 1):C332-9. doi: 10.1152/ajpcell.1990.259.2.C332.
10
Synthesis and calcium channel antagonist activity of 3-arylmethyl 5-isopropyl 1,4-dihydro-2,6-dimethyl-4-(pyridyl)-3,5-pyridinedicarboxylates.3-芳基甲基5-异丙基-1,4-二氢-2,6-二甲基-4-(吡啶基)-3,5-吡啶二甲酸酯的合成及钙通道拮抗剂活性
Pharm Res. 1990 Sep;7(9):919-22. doi: 10.1023/a:1015941706008.
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