【摘要】：新藥創(chuàng)制是復雜的智力活動,涉及科學研究、技術創(chuàng)造、產品開發(fā)和醫(yī)療效果等多維科技活動。每個藥物都有自身的研發(fā)軌跡,而構建化學結構是最重要的環(huán)節(jié),因為它涵蓋了藥效、藥代、安全性和生物藥劑學等性質。本欄目以藥物化學視角,對有代表性的藥物的成功構建,加以剖析和解讀。根據酶-底物復合物的結構和酶催化反應的過渡態(tài)結構特征設計合成的扎那米韋、奧司他韋和帕拉米韋,是理性藥物設計中具有教科書式的范例。它們都是從流感神經氨酸苷酶——唾液酸晶體結構提供的信息出發(fā),各自采用了不同的策略和方法,經歷了不同的研發(fā)路徑,在同一年內獲得了成功。三個藥物的結構骨架不同,而藥效團的分布非常相似,在運用結構生物學、計算化學和藥物化學方法和技術的結合上,給人們許多啟示。
[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. Zanamivir oseltamivir and paramivir which are designed and synthesized according to the structure of enzyme substrate complex and the transition structure of enzymatic catalytic reaction are textbook examples in rational drug design. Starting from the information provided by the crystal structure of influenza neuraminidase-sialic acid, each of them has adopted different strategies and methods, experienced different research and development paths, and achieved success in the same year. The structural skeletons of the three drugs are different, and the distribution of pharmacophore is very similar. The combination of structural biology, computational chemistry and pharmacochemical methods and techniques has given us a lot of enlightenment.
【作者單位】： 中國醫(yī)學科學院藥物研究所;
【分類號】：R914

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