以药物化学方法研发的首创药物苏沃雷生

发布时间：2018-01-16 14:29

本文关键词：以药物化学方法研发的首创药物苏沃雷生　出处：《药学学报》2016年12期 　论文类型：期刊论文

【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。2014年上市的苏沃雷生,无论在策略上还是实施上都是一个"摸着石头过河"的原创性药物的研发实例。基于配体-受体的生物功能研制药物往往因多重生理功能而改变研究方向和目标,以多肽食欲素-受体为靶标的新药研究由减肥药转向为催眠药,乃至研制成功,就是一个范例。从300万个化合物随机筛选出苗头化合物,到用药物化学方法和分析构效关系作结构变换,在活性方面,要对双靶标有相同(近)的活性,在受体的分子水平和功能的细胞水平上优化出高活性化合物,并对实验动物的睡眠/觉醒有良好的调节作用。在成药性上,吸收性、代谢性、安全性等多方面的一步步优化,显示出研发者的学术严谨性和技术娴熟性。全新的靶标和首创的药物在实验室、临床和市场曾经并继续受到审视,因为一个药物靶标的确证还要到"真实世界"大范围考量。
[Abstract]:Drug discovery is a complicated intellectual activity, involving scientific research, technology creation, product development and effect of multi-dimensional medical science and technology activities. Each drug has its own development trajectory and the construction of chemical structure, is the most important link, because it covers the pharmacodynamics, pharmacokinetics, safety and biopharmaceutical properties. In this column from the perspective of medicinal chemistry, the representative drug is successfully constructed to analyze and interpret the.2014 listed suvo Lei, both in strategy and implementation are the original drug a "stones" research examples. The biological function of the ligand receptor drugs often due to multiple physiological function change the research direction and goal based on the orexin receptor peptide to study drug targets by weight-loss drug to hypnotic, and even developed, is a good example. From 3 million randomly selected compounds Signs of compounds, to pharmaceutical chemistry and structure-activity relationship analysis method for structural transformation, in terms of activity, to be marked with the same double target (near) activity at the molecular level and the function of the receptor on the cell level optimization of high active compounds, and the experimental animal sleep / wake have the good effect. In medicine, absorption, metabolism and many other aspects of security step by step optimization, showing the academic rigor and a skilled R & D researchers. The new target and the first drug in the laboratory, clinical and market have been and continue to be scrutinized, as confirmed a drug target but also to the real world "a wide range of considerations.

【作者单位】：中国医学科学院北京协和医学院药物研究所;
【分类号】：R914
【正文快照】： 1 背景 1998年美国霍华德休斯医学研究中心(HHMI)发现了一种肽类神经递质,命名为下视丘泌素(hypocretin)(De Lecea L,Kilduff TS,Peyron C,et al.Proc Natl Acad Sci U S A,1998,95:322-327),是源于在下丘脑(hypothalamus)发现了特异性的mR NA。同年Scrips研究所也独立发现了

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