Cyclobutanes in Small-Molecule Drug Candidates

被引：116
作者：
van der Kolk, Marnix R. [1 ]
Janssen, Mathilde A. C. H. [1 ]
Rutjes, Floris P. J. T. [1 ]
Blanco-Ania, Daniel [1 ]
机构：
[1] Radboud Univ Nijmegen, Inst Mol & Mat, Heyendaalseweg 135, NL-6526 AJ Nijmegen, Netherlands
来源：
CHEMMEDCHEM | 2022年 / 17卷 / 09期
基金：
荷兰研究理事会;
关键词：
Cyclobutanes; strained carbocycles; conformational restriction; pharmacophores; isosteres; HISTAMINE H-3 RECEPTOR; GLYCOGEN-SYNTHASE KINASE-3; APOLIPOPROTEIN-E; GLUCOKINASE ACTIVATORS; BIOLOGICAL EVALUATION; HISTONE MODIFICATIONS; SELECTIVE INHIBITORS; INDAZOLE DERIVATIVES; STRUCTURAL BASIS; POTENTIAL ROLE;
D O I：
10.1002/cmdc.202200020
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
Cyclobutanes are increasingly used in medicinal chemistry in the search for relevant biological properties. Important characteristics of the cyclobutane ring include its unique puckered structure, longer C-C bond lengths, increased C-C pi-character and relative chemical inertness for a highly strained carbocycle. This review will focus on contributions of cyclobutane rings in drug candidates to arrive at favorable properties. Cyclobutanes have been employed for improving multiple factors such as preventing cis/trans-isomerization by replacing alkenes, replacing larger cyclic systems, increasing metabolic stability, directing key pharmacophore groups, inducing conformational restriction, reducing planarity, as aryl isostere and filling hydrophobic pockets.
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页数：22
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