Applications of Fluorine in Medicinal Chemistry
Applications of Fluorine in Medicinal Chemistry
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DOI：
10.1021/acs.jmedchem.5b00258
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发表时间：
2015-11-12
影响因子：
7.3
通讯作者：
Meanwell, Nicholas A.
中科院分区：
文献类型：
--
作者：
Gillis, Eric P.;Eastman, Kyle J.;Meanwell, Nicholas A.
氟在药物设计和开发中的作用正在迅速扩大，因为我们更多地了解了与这种不同寻常的元素相关的独特性质，以及如何以更复杂的方式使用它。在分子中适当地引入氟可以有效地影响构象、pK(A)、内在效力、膜通透性、代谢途径和药代动力学性质。此外，F-18已被确定为一种有用的正电子发射同位素，可与体内成像技术一起使用，这一技术可能在药物发现和开发中有广泛的应用，但通常仅限于标记化合物的方便合成可及性。氟在药物设计中的广泛应用为开发新的合成方法提供了强有力的刺激，使人们能够更容易地获得各种含氟化合物。在这篇综述中，我们提供了氟在药物分子中的战略性掺入的影响以及在正电子发射断层扫描中的应用的最新进展。
The role of fluorine in drug design and development is expanding rapidly as we learn more about the unique properties associated with this unusual element and how to deploy it with greater sophistication. The judicious introduction of fluorine into a molecule can productively influence conformation, pK(a), intrinsic potency, membrane permeability, metabolic pathways, and pharmacokinetic properties. In addition, F-18 has been established as a useful positron emitting isotope for use with in vivo imaging technology that potentially has extensive application in drug discovery and development, often limited only by convenient synthetic accessibility to labeled compounds. The wide ranging applications of fluorine in drug design are providing a strong stimulus for the development of new synthetic methodologies that allow more facile access to a wide range of fluorinated compounds. In this review, we provide an update on the effects of the strategic incorporation of fluorine in drug molecules and applications in positron emission tomography.