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首页> 外文期刊>Pharmaceutical Chemistry Journal >SYNTHESIS AND PRELIMINARY EVALUATION OF AFFINITY TO RETINOIC ACID RECEPTORS FOR NEW ORGANOSILICON-BASED RETINOIDS
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SYNTHESIS AND PRELIMINARY EVALUATION OF AFFINITY TO RETINOIC ACID RECEPTORS FOR NEW ORGANOSILICON-BASED RETINOIDS

机译：基于有机硅的新型视黄醛对视黄酸受体的亲和力合成及初步评估

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摘要

Facile synthetic routes to new silicon-containing ligands (1-4) for retinoic acid receptors (RARs) are reported. The design of these RAR ligands is based on a pharmacophoric model that divides the molecules into three regions (A, B, and C). The series of ligands is unique in region A due to their acyclic nature and the presence of alkyl-substituted silicon at the core. Substituted silyl groups that are generally viewed as protecting groups are used to fulfill pharmacophore requirements. Various alkyl substituents available on the silicon starting materials afford an opportunity to explore steric effects on binding. In region B of ligands 1-4, a cinnamate moiety maintains some degree of conjugation and planarity in the molecules. A biaryl group used in region B of another series of compounds is reported to lead to RARb selectivity. Finally, region C of the ligands contains a carboxylate group, a well know pharmacophore requirement for RAR ligands. The compounds prepared in this work were found to have micromolar to nanomolar affinity for these medically relevant target receptors. The proposed silane-containing ligands 'represent a new series of siloacetylenic aryl acids that are worth of further investigation. They may serve as leads for the development of higher-affinity, more receptor-selective agents.
机译：据报道，对于视黄酸受体（RARs）而言，合成新的含硅配体（1-4）的简便合成路线。这些RAR配体的设计基于药效学模型，该模型将分子分为三个区域（A，B和C）。由于其无环性质和在核心存在烷基取代的硅，一系列配体在区域A中是独特的。通常被视为保护基的取代的甲硅烷基用于满足药效基团的要求。硅原料上可用的各种烷基取代基提供了探索对结合的空间效应的机会。在配体1-4的区域B中，肉桂酸酯部分在分子中保持一定程度的缀合和平面度。据报道，在另一系列化合物的区域B中使用的联芳基会导致RARb选择性。最后，配体的区域C包含羧酸酯基团，这是RAR配体的众所周知的药效基团要求。发现在这项工作中制备的化合物对这些医学上相关的靶受体具有微摩尔至纳摩尔的亲和力。提出的含硅烷的配体代表了一系列新的硅烷炔基芳基酸，值得进一步研究。它们可以充当开发更高亲和力，更多受体选择剂的先导。

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