Phenols in Pharmaceuticals: Analysis of a Recurring Motif
Phenols in Pharmaceuticals: Analysis of a Recurring Motif
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DOI：
10.1021/acs.jmedchem.2c00223
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发表时间：
2022-05-26
影响因子：
7.3
通讯作者：
Njardarson, Jon T.
中科院分区：
文献类型：
--
作者：
Scott, Kevin A.;Cox, Philip B.;Njardarson, Jon T.
酚类和酚醚是重要的支架材料，在自然界和已批准的小分子药物中重复出现。本概要首次对美国FDA批准的含有苯酚或酚醚碎片的分子结构进行了全面的汇编和分析。这个数据集包括371个结构，这些结构由天然产物强烈代表。在这里描述的化合物中，共有55种在世界卫生组织的基本药物清单上。结构分析揭示了酚类和酚醚赋予的物理化学性质的显著差异，每种物质在药物开发方面都有优点和缺点。尽管在过去的十年里，药物先导中的SP(3)中心的比例有增加的趋势，从而“逃离平原”，但在2020年批准的小分子药物中，酚类和酚醚的比例为62%，这表明这种芳香族部分在药物和天然产品中具有特殊的地位。
Phenols and phenolic ethers are significant scaffolds recurring both in nature and among approved small-molecule pharmaceuticals. This compendium presents the first comprehensive compilation and analysis of the structures of U.S. FDA-approved molecules containing phenol or phenolic ether fragments. This dataset comprises 371 structures, which are strongly represented by natural products. A total of 55 of the compounds described here are on the World Health Organization's list of essential medicines. Structural analysis reveals significant differences in the physicochemical properties imparted by phenols versus phenol ethers, each having benefits and drawbacks for drug developability. Despite trends over the past decade to increase the fraction of sp(3) centers in drug leads, thereby "escaping flatland", phenols and phenolic ethers are represented in 62% of small-molecule drugs approved in 2020, suggesting that this aromatic moiety holds a special place in drugs and natural products.