Akamatsu Miki
Division of Environmental Science and Technology, Graduate School of Agriculture, Kyoto University, Kitashirakawa-oiwake-cho, Sakyo-ku, Kyoto, 606-8502, Japan.
Curr Top Med Chem. 2002 Dec;2(12):1381-94. doi: 10.2174/1568026023392887.
Quantitative structure-activity relationships (QSAR) have played an important role in the design of pharmaceuticals and agrochemicals. All QSAR techniques assume that all the compounds used in analyses bind to the same site of the same biological target. However, each method differs in how it describes structural properties of compounds and how it finds the quantitative relationships between the properties and activities. The Hansch-Fujita approach, the so-called classical QSAR, is a representative of QSAR methods. Despite the usefulness, classical QSAR techniques cannot be applied to all datasets due to the lack of availability of physicochemical parameters of the whole molecule or its substituents and often it is difficult to estimate those values. In addition, molecular properties based on the three dimensional (3D) structure of compounds may be useful in describing the ligand-receptor interactions. Recently, a variety of ligand-based 3D-QSAR methods such as Comparative Molecular Field Analysis (CoMFA) have been developed and widely used in medicinal chemistry. This review describes different 3D-QSAR techniques and indicates their advantages and disadvantages. Several studies about 3D-QSAR of ADME-toxicity and perspective of 3D-QSAR are also described in this review.
定量构效关系（QSAR）在药物和农用化学品设计中发挥了重要作用。所有QSAR技术都假定分析中使用的所有化合物都与同一生物靶点的同一部位结合。然而，每种方法在描述化合物的结构性质以及如何找到性质与活性之间的定量关系方面有所不同。Hansch-Fujita方法，即所谓的经典QSAR，是QSAR方法的代表。尽管很有用，但由于缺乏整个分子或其取代基的物理化学参数，经典QSAR技术不能应用于所有数据集，而且通常很难估计这些值。此外，基于化合物三维（3D）结构的分子性质可能有助于描述配体-受体相互作用。最近，已经开发了多种基于配体的3D-QSAR方法，如比较分子场分析（CoMFA），并在药物化学中广泛使用。本综述描述了不同的3D-QSAR技术，并指出了它们的优缺点。本综述还描述了一些关于ADME毒性的3D-QSAR研究以及3D-QSAR的前景。
