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

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.

Automated summary

This review discusses the increasing use of aliphatic three- and four-membered rings in medicinal chemistry, highlighting both their advantages and potential risks. Understanding the characteristics of small ring structures is crucial for enhancing the efficacy and safety of pharmaceuticals.