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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。防止血栓形成的药物可以通过阻断血小板聚集的不同环节或靶标而实现,沃拉帕沙是第一个作用于蛋白酶激活受体的拮抗剂,防止血栓形成的口服小分子药物。本品研制成功给我们的启示是:结构复杂的天然产物作为先导物进行优化的一个重要前提是实现高效率的全合成,从而可以自如地改造或修饰结构乃至多个手性中心的化合物。由有初步活性的喜巴辛到手性中心完全翻转改变和加入了重要结构片段,首创性地完成了沃拉帕沙研制,药物化学方法展现了精雕细刻式的对活性与成药性的飞跃。
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. Drugs that prevent thrombosis can be achieved by blocking different aspects or targets of platelet aggregation. Valapresti is the first oral small-molecule drug that acts on antagonists of protease-activated receptors and prevents thrombosis. The successful development of this product gives us some enlightenment: One of the most important preconditions for optimizing the structure of complex natural products as precursors is to realize efficient and total synthesis, so that compounds with structural or even chiral centers can be easily modified or modified. By the initial activity of Hibiscus to the chiral center complete flip change and added important structural fragments, the first to complete the development of the Volapapa, the drug chemistry shows a carved of the activity of the drug and a significant leap .