1,4-Dihydropyridines as Calcium Channel Ligands and Privileged Structures
1,4-Dihydropyridines as Calcium Channel Ligands and Privileged Structures
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DOI：
10.1023/a:1023632419813
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发表时间：
2003-06
影响因子：
4
通讯作者：
D. Triggle
中科院分区：
文献类型：
--
作者：
D. Triggle
1.1，4-二氢吡啶核团作为重要的心血管药物--钙拮抗剂--硝苯地平、尼群地平、氨氯地平和尼索地平的支架，通过作用于CaV_1(L型)电压门控钙通道发挥降压和抗心绞痛作用。这些药物作用于特定的受体部位，存在明确的构效关系，包括立体选择性。尽管CaV1类通道广泛存在，但钙拮抗剂在心血管系统中表现出显著的选择性作用。这种选择性是由多种因素引起的，包括通道亚型、状态依赖的相互作用、药代动力学和钙动员方式。1，4-二氢吡啶核也是一种特权结构或支架，当适当修饰取代基时，它可以与不同的受体和离子通道相互作用，包括钾和钠通道以及G蛋白类受体。
1. The 1,4-dihydropyridine nucleus serves as the scaffold for important cardiovascular drugs—calcium antagonists—including nifedipine, nitrendipine, amlodipine, and nisoldipine, which exert their antihypertensive and antianginal actions through actions at voltage-gated calcium channels of the CaV1 (L-type) class.2. These drugs act at a specific receptor site for which defined structure-activity relationships exist, including stereoselectivity.3. Despite the widespread occurrence of the CaV1 class of channel, the calcium antagonists exhibit significant selectivity of action in the cardiovascular system. This selectivity arises from a number of factors including subtype of channel, state-dependent interactions, pharmacokinetics, and mode of calcium mobilization.4. The 1,4-dihydropyridine nucleus is also a privileged structure or scaffold that can, when appropriately decorated substituents, interact at diverse receptors and ion channels, including potassium and sodium channels and receptors of the G-protein class.