理性设计的西咪替丁

发布时间：2018-05-14 07:02

本文选题：新药创制 + 物化性质　；参考：《药学学报》2015年03期

【摘要】：新药创制是复杂的智力活动,涉及科学研究、技术创造、产品开发和医疗效果等多维科技活动。每个药物都有自身的研发轨迹,而构建化学结构是最重要的环节,因为它涵盖了药效、药代、安全性和生物药剂学等性质。本栏目以药物化学视角,对有代表性的药物的成功构建,加以剖析和解读。在缺乏受体信息的情况下,以天然配体为出发点,在结构的变换和活性的变化中,逐渐演化出先导物,以及实施先导物的优化。理性药物设计不只限于计算机辅助的手段,构效关系可以在多层次上进行分析,化学结构、构象特征、功能基(药效团)分布、物化性质等,都可成为演绎和优化结构的依据。西咪替丁是理性药物设计的另一种典范,充分应用了药物化学原理,如同系律、电子等排原理、拼合原理等。首创性药物的可贵在于没有借鉴和参考下开辟了一个新的治疗领域,包括靶标的确证和药物的成功。也由于首创药物未能充分优化,存在不足之处,为后续研发的替丁留下了空间,在模拟中后来居上。
[Abstract]:New drug creation is a complex intellectual activity involving multi-dimensional scientific and technological activities such as scientific research, technological creation, product development and medical effects. Each drug has its own R & D track, and the construction of chemical structures is the most important step because it covers pharmacodynamics, pharmacology, safety and biopharmaceutical properties. This column analyzes and interprets the successful construction of representative drugs from the perspective of drug chemistry. In the absence of receptor information, with the natural ligands as the starting point, in the transformation of the structure and the change of activity, the leader gradually evolved, and the optimization of the precursor was carried out. Rational drug design is not limited to computer-aided means. Structure-activity relationships can be analyzed at multiple levels, chemical structure, conformational characteristics, functional group (pharmacophore) distribution, physicochemical properties and so on, all of which can be used as the basis for deducing and optimizing the structure. Cimetidine is another model of rational drug design, which makes full use of the principles of pharmacochemistry, such as system law, electronic equal-arrangement principle, splicing principle and so on. The value of pioneering drugs lies in the opening up of a new field of treatment without reference, including the confirmation of targets and the success of drugs. Because the original drug is not fully optimized, there are some shortcomings, which leave room for the subsequent research and development of tetidine, and become better in the simulation.
【作者单位】：中国医学科学院药物研究所;
【分类号】：R975

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