Amide Bond Bioisosteres: Strategies, Synthesis, and Successes.
Amide Bond Bioisosteres: Strategies, Synthesis, and Successes.
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DOI：
10.1021/acs.jmedchem.0c00530
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发表时间：
2020-11-12
影响因子：
7.3
通讯作者：
Trippier PC
中科院分区：
文献类型：
--
作者：
Kumari S;Carmona AV;Tiwari AK;Trippier PC
酰胺官能团在生物分子（包括许多临床批准的药物）的组成中起着关键作用。生物电子等排体原理在先导化合物的合理修饰中应用广泛，用于提高效力、增强选择性、改善药代动力学性质、消除毒性以及获取新的化学空间以确保知识产权。引入生物电子等排体可导致分子大小、形状、电子分布、极性、pKa、偶极或极化率等结构变化，这些变化对生物活性可能有利，也可能有害。这种方法为药物设计与研发开辟了新途径，使得更多高效的候选药物进入市场以及临床研发阶段。在此，我们综述了选择酰胺生物电子等排体的策略考量（原因）、每种等排体的合成路线（方法）以及每种生物电子等排体的成功案例（应用），以便为药物化学家全面介绍这一重要的工具库。
The amide functional group plays a key role in the composition of biomolecules, including many clinically approved drugs. Bioisosterism is widely employed in the rational modification of lead compounds, being used to increase potency, enhance selectivity, improve pharmacokinetic properties, eliminate toxicity, and acquire novel chemical space to secure intellectual property. The introduction of a bioisostere leads to structural changes in molecular size, shape, electronic distribution, polarity, pKa, dipole or polarizability, which can be either favorable or detrimental to biological activity. This approach has opened up new avenues in drug design and development resulting in more efficient drug candidates introduced onto the market as well as in the clinical pipeline. Herein, we review the strategic decisions in selecting an amide bioisostere (the why), synthetic routes to each (the how), and success stories of each bioisostere (the implementation) to provide a comprehensive overview of this important toolbox for medicinal chemists.
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影响因子：
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