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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。西米匹韦是继特拉匹韦与波西匹韦(本刊2014,7:1084-1088;2014,8:1208-1210)FDA批准的第三个丙肝治疗药,虽然作用靶标相同,但结构类型为大环化合物,不含有亲电性基团,不与酶发生共价结合。本品也是以酶的裂解产物多肽为起始物,但由六肽演化成非肽性口服药物的过程中,进行了药物化学、结构生物学、分子模拟、有机合成等多学科领域的研究,体现了新药研究的鲜明个性、复杂性和风险性。
The creation of new drugs 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 development trajectory, and the construction of the chemical structure is the most important part, because it covers the properties such as efficacy, drug substitution, safety and biopharmaceutical. This column from the perspective of medicinal chemistry, representative of the successful construction of drugs, to be analyzed and interpreted. Simicavir is the third HCV drug approved by the FDA following telaprevir and positidine (publication 2014, 7: 1084-1088; 2014, 8: 1208-1210). Although the targets of action are the same, Structure type macrocyclic compound, does not contain electrophilic groups, not covalently bonded with the enzyme. This product is also based on the enzymatic cleavage product peptide as starting material, but in the process of evolution of hexapeptide into non-peptide oral drug, the research in multidisciplinary fields such as drug chemistry, structural biology, molecular simulation and organic synthesis has been conducted. Embodies the distinctive personality of new drug research, complexity and risk.