维甲类化合物构效关系研究-──维甲X受体特异性配体的二维和三维定量构效关系研究

STUDIES ON THE STRUCTUREACTIVITY RELATIONSHIP OF RETINOIDS HANSCH ANALYSIS AND 3DQSAR STUDIES ON SPECIFIC LIGANDS OF RETINOID X RECEPTOR

定向地设计作用于特定受体的维甲配体分子对于阐明维甲作用的分子机制、合成新作用类型的维甲类化合物有重要意义。本文在研究系列维甲Ｘ受体特异性配体的二维与三维构效关系的基础上，考察了维甲Ｘ核受体对其配体的结构及电性需求，以进一步指导设计和合成特异性的维甲Ｘ受体激动剂。

Retinoids (Vitamin A, its metabolites and synthetic analogues) play important roles in a variety of biological processes, including cellular differentiation, proliferation and apoptosis. The many diverse actions of retionids attribute to the ability of regulating transcription of different target genes through activation of multiple retinoid nuclear receptors (RAR of RXR). So, retinoids with selective binding ability to specific receptor may not only have improved therapeutic indices, but may also be invaluable for elucidating the molecular mechanism of retinoidal transcriptional activation. Based on the two dimensional and three dimensional quantitive structureactivity relationships of specific ligands of RXR, we carried out mimesis of enviroment of ligands interacting with their receptor and, to some extent, mapping the topological and physicochemical characteristics of receptor. The knowledge of the QSAR study will offer detailed molecular information for design, synthesis and biological evaluation in drug research and development.