Defining optimum lipophilicity and molecular weight ranges for drug candidates-Molecular weight dependent lower logD limits based on permeability
Defining optimum lipophilicity and molecular weight ranges for drug candidates-Molecular weight dependent lower logD limits based on permeability
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DOI：
10.1016/j.bmcl.2009.03.109
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发表时间：
2009-05-15
影响因子：
2.7
通讯作者：
Waring, Michael J.
中科院分区：
文献类型：
--
作者：
Waring, Michael J.
使用各种统计技术对结构多样的大型 Caco-2 渗透性数据集进行分析表明，logD 和分子量是确定候选药物渗透性的最重要因素。 logD 的限制显示取决于分子量。这些限制被证明在增加发现高渗透性化合物的机会方面可能优于当前的指导方针。当与文献中基于避免毒理学和其他不利影响而建议的亲脂性上限相结合时，这有助于 de。 ne 是候选药物的最佳亲脂性范围。 (C) 2009 Elsevier Ltd. 保留所有权利。
Analysis of a large, structurally diverse Caco-2 permeability dataset using a variety of statistical techniques suggests that logD and molecular weight are the most important factors in determining the permeability of drug candidates. The limit for logD is shown to be dependent on molecular weight. These limits are shown to be potentially superior to current guidelines in increasing the chances of finding highly permeable compounds. When combined with suggested upper limits for lipophilicity suggested in the literature based on the avoidance of toxicology and other adverse effects, this helps de. ne a lipophilicity range that is optimum for drug candidates. (C) 2009 Elsevier Ltd. All rights reserved.