为其戴上一环：小脂肪族环在药物化学中的应用
Put a ring on it: application of small aliphatic rings in medicinal chemistry.
作者信息
Bauer Matthias R, Di Fruscia Paolo, Lucas Simon C C, Michaelides Iacovos N, Nelson Jennifer E, Storer R Ian, Whitehurst Benjamin C
机构信息
Discovery Sciences, BioPharmaceuticals R&D, AstraZeneca Cambridge UK
出版信息
RSC Med Chem. 2021 Jan 7;12(4):448-471. doi: 10.1039/d0md00370k. eCollection 2021 Apr 28.
Abstract
Aliphatic three- and four-membered rings including cyclopropanes, cyclobutanes, oxetanes, azetidines and bicyclo[1.1.1]pentanes have been increasingly exploited in medicinal chemistry for their beneficial physicochemical properties and applications as functional group bioisosteres. This review provides a historical perspective and comparative up to date overview of commonly applied small rings, exemplifying key principles with recent literature examples. In addition to describing the merits and advantages of each ring system, potential hazards and liabilities are also illustrated and explained, including any significant chemical or metabolic stability and toxicity risks.
摘要
脂肪族三元和四元环，包括环丙烷、环丁烷、氧杂环丁烷、氮杂环丁烷和双环[1.1.1]戊烷，因其有益的物理化学性质以及作为官能团生物电子等排体的应用，在药物化学中得到了越来越广泛的应用。本综述提供了一个历史视角，并对常用小环进行了最新的比较概述，用近期文献实例说明了关键原理。除了描述每个环系的优点和优势外，还阐述并解释了潜在的危害和缺点，包括任何重大的化学或代谢稳定性以及毒性风险。
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