發(fā)布時(shí)間：2018-11-08 10:02

【摘要】：新藥創(chuàng)制是復(fù)雜的智力活動(dòng),涉及科學(xué)研究、技術(shù)創(chuàng)造、產(chǎn)品開發(fā)和醫(yī)療效果等多維科技活動(dòng)。每個(gè)藥物都有自身的研發(fā)軌跡,而構(gòu)建化學(xué)結(jié)構(gòu)是最重要的環(huán)節(jié),因?yàn)樗w了藥效、藥代、安全性和生物藥劑學(xué)等性質(zhì)。本欄目以藥物化學(xué)視角,對(duì)有代表性的藥物的成功構(gòu)建,加以剖析和解讀。根據(jù)酶-底物復(fù)合物的結(jié)構(gòu)和酶催化反應(yīng)的過渡態(tài)結(jié)構(gòu)特征設(shè)計(jì)合成的扎那米韋、奧司他韋和帕拉米韋,是理性藥物設(shè)計(jì)中具有教科書式的范例。它們都是從流感神經(jīng)氨酸苷酶——唾液酸晶體結(jié)構(gòu)提供的信息出發(fā),各自采用了不同的策略和方法,經(jīng)歷了不同的研發(fā)路徑,在同一年內(nèi)獲得了成功。三個(gè)藥物的結(jié)構(gòu)骨架不同,而藥效團(tuán)的分布非常相似,在運(yùn)用結(jié)構(gòu)生物學(xué)、計(jì)算化學(xué)和藥物化學(xué)方法和技術(shù)的結(jié)合上,給人們?cè)S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(xué)科學(xué)院藥物研究所;
【分類號(hào)】：R914

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