Log P as a tool in intramolecular hydrogen bond considerations.
Log P as a tool in intramolecular hydrogen bond considerations.
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DOI：
10.1016/j.ddtec.2018.03.001
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发表时间：
2018-07-01
期刊：
影响因子：
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通讯作者：
Ermondi, Giuseppe
中科院分区：
文献类型：
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作者：
Caron, Giulia;Vallaro, Maura;Ermondi, Giuseppe
分子内氢键（IMHB）的考虑因素在药物发现中越来越重要，需要一种可以很早预测化合物形成IMHB的能力的分子描述符来加速候选药物的优化过程。虽然log Poct主要用于优化目的，但在本文中，我们首先使用块相关性（BR）分析从理论上说明log Poct不是评估候选IMHB属性的方便选择。然后讨论了log Poct的极限，并引入了Deltalog Poct-tol，即log Poct与log Ptol（甲苯/水体系中分配系数的对数）之间的差值。最后，我们提供了一些例子，也包括bRo 5蛋白酶抑制剂，以澄清如何解释Deltalog Poct-tol值。
Intramolecular hydrogen bonding (IMHB) considerations are gaining relevance in drug discovery and a molecular descriptor which can predict very early the capacity of a compound to form IMHB is needed to speed up the optimization process of drug candidates. Although log Poct is largely used for optimization purposes, in this paper we firstly use the Block Relevance (BR) analysis to theoretically show how log Poct is not a convenient choice to assess IMHB properties of candidates. Then we discuss the limits of log Poct and introduce Deltalog Poct-tol, i.e. the difference between log Poct and log Ptol (the logarithm of the partition coefficient in the toluene/water system). Finally, we provided some examples also including bRo5 protease inhibitors, to clarify how to interpret Deltalog Poct-tol values.