骨架跃迁在药物发现中的应用

骨架跃迁概述

药物发现的总体目标是快速鉴定新化合物，这些化合物对与疾病相关的预先选定的生物靶点具有足够的安全性和类药物特性。骨架跃迁是现代药物化学合理设计药物的中心任务，被药物化学家广泛用于寻找具有新骨架和改善已知苗头化合物分子性质的等价化合物。骨架跃迁中最常用的方法包括基于结构的跃迁(图1)^[1,2]，杂环替换(图2)^[3]，环打开(图3)^[4]或环闭合(图4)^[4]，等等。

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图2 用杂环替代法发现一种新的JAK1抑制剂

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图3. 使用开环方法发现新的酪氨酸激酶抑制剂

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图4. 使用环闭合方法发现新的前列腺素EP1受体拮抗剂

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