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Cyclobutanes in Small‐Molecule Drug Candidates
Author(s) -
Kolk Marnix R.,
Janssen Mathilde A. C. H.,
Rutjes Floris P. J. T.,
BlancoAnia Daniel
Publication year - 2022
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.202200020
Subject(s) - cyclobutanes , cyclobutane , pharmacophore , chemistry , planarity testing , stereochemistry , isomerization , ring (chemistry) , molecule , isostere , ring size , computational chemistry , crystallography , organic chemistry , catalysis
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 π‐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.