Put a ring on it: application of small aliphatic rings in medicinal chemistry

被引：280

作者：

Bauer, Matthias R. ^{[1
]}

Di Fruscia, Paolo ^{[1
]}

Lucas, Simon C. C. ^{[1
]}

Michaelides, Iacovos N. ^{[1
]}

Nelson, Jennifer E. ^{[1
]}

Storer, R. Ian ^{[1
]}

Whitehurst, Benjamin C. ^{[1
]}

机构：

[1] AstraZeneca, Discovery Sci, BioPharmaceut R&D, Cambridge, England

来源：

RSC MEDICINAL CHEMISTRY | 2021年 / 12卷 / 04期

关键词：

INDUCED PROTEIN-DEGRADATION; IN-VIVO EFFICACY; DRUG DISCOVERY; BRAIN PENETRANT; HIGHLY POTENT; BIOLOGICAL EVALUATION; PDE10A INHIBITORS; DESIGN; OXETANES; KINASE;

D O I：

10.1039/d0md00370k

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：448 / 471

页数：24

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