Current state and perspectives of 3D-QSAR

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.