Worldwide Medicinal Chemistry, Pfizer Worldwide Research & Development, 610 Main Street, Cambridge, MA 02139, United States.
Bioorg Med Chem Lett. 2020 Dec 1;30(23):127503. doi: 10.1016/j.bmcl.2020.127503. Epub 2020 Aug 25.
Among the most devastating disorders of our time, neurologic and psychiatric diseases combine to cause more disability than any other disease area. One of the key objectives within the medicinal chemistry discipline is to design molecules that penetrate into the target tissue. The objective of tissue specificity can be to gain or restrict drug access to the compartment of interest. This article briefly reviews the progress of CNS drug discovery over the past few decades. Included are the most recent efforts to harness structural and physicochemical properties assessment coupled with the impact of efflux transporters in determining brain penetration and the translation from rodent to human brain tissue targeting.
在我们这个时代最具破坏性的疾病中，神经和精神疾病相结合导致的残疾比任何其他疾病领域都多。药物化学学科的主要目标之一是设计能够穿透靶组织的分子。组织特异性的目标可以是增加或限制药物进入感兴趣的隔室的机会。本文简要回顾了过去几十年中枢神经系统药物发现的进展。其中包括利用结构和物理化学性质评估以及外排转运体的影响来确定脑穿透性，并将啮齿动物脑组织靶向转化为人体的最新努力。
