Acetylene Group, Friend or Foe in Medicinal Chemistry
Acetylene Group, Friend or Foe in Medicinal Chemistry
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DOI：
10.1021/acs.jmedchem.9b01617
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发表时间：
2020-06-11
影响因子：
7.3
通讯作者：
Talele, Tanaji T.
中科院分区：
文献类型：
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作者：
Talele, Tanaji T.
在药物化学中使用乙炔（乙炔）基团恰逢1959年《药物化学杂志》的创刊。从那时起，乙炔基团在药物发现和开发中得到了广泛的利用。因此，它已被认为是一种特殊的结构特征，可靶向广泛的治疗靶蛋白，包括MAO、酪氨酸激酶、BACE1、类固醇受体、mGlu5受体、FFA1/GPR40和HIV-1 rt。此外，末端炔功能经常被引入化学生物学探针中，作为点击手柄来识别分子靶标并评估靶标接合。本展望分为三个部分，包括：(1)乙基的理化性质，(2)乙基在药物化学中的优缺点，以及(3)乙基对化学生物学方法的影响。
The use of an acetylene (ethynyl) group in medicinal chemistry coincides with the launch of the Journal of Medicinal Chemistry in 1959. Since then, the acetylene group has been broadly exploited in drug discovery and development. As a result, it has become recognized as a privileged structural feature for targeting a wide range of therapeutic target proteins, including MAO, tyrosine kinases, BACE1, steroid receptors, mGlu5 receptors, FFA1/GPR40, and HIV-1 RT. Furthermore, a terminal alkyne functionality is frequently introduced in chemical biology probes as a click handle to identify molecular targets and to assess target engagement. This Perspective is divided into three parts encompassing: (1) the physicochemical properties of the ethynyl group, (2) the advantages and disadvantages of the ethynyl group in medicinal chemistry, and (3) the impact of the ethynyl group on chemical biology approaches.