{"title":"The roles of fused-cyclopropanes in medicinal chemistry: Insights from the past decade","authors":"Dongsheng Li","doi":"10.1016/j.ejmech.2025.117951","DOIUrl":null,"url":null,"abstract":"<div><div>Fused-cyclopropane rings have become increasingly prevalent in modern drug discovery and medicinal chemistry campaigns as they can provide inherent three-dimensionality, structural novelty, and unique physicochemical properties. This review presents an overview of examples from the primary medicinal chemistry literature over the past decade to illustrate diverse applications of fused-cyclopropane ring motifs, including (a) enhanced metabolic stability, (b) improved target binding potency, (c) novel chemotype generation, (d) reduced off-target effects, (e) increased membrane/blood-brain barrier (BBB) permeability, (f) improved hydrolytic stability, (g) mitigated toxicity liability, (h) enhanced chemical stability, and (i) improved aqueous solubility.</div></div>","PeriodicalId":314,"journal":{"name":"European Journal of Medicinal Chemistry","volume":"297 ","pages":"Article 117951"},"PeriodicalIF":6.0000,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"European Journal of Medicinal Chemistry","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0223523425007160","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CHEMISTRY, MEDICINAL","Score":null,"Total":0}
引用次数: 0
Abstract
Fused-cyclopropane rings have become increasingly prevalent in modern drug discovery and medicinal chemistry campaigns as they can provide inherent three-dimensionality, structural novelty, and unique physicochemical properties. This review presents an overview of examples from the primary medicinal chemistry literature over the past decade to illustrate diverse applications of fused-cyclopropane ring motifs, including (a) enhanced metabolic stability, (b) improved target binding potency, (c) novel chemotype generation, (d) reduced off-target effects, (e) increased membrane/blood-brain barrier (BBB) permeability, (f) improved hydrolytic stability, (g) mitigated toxicity liability, (h) enhanced chemical stability, and (i) improved aqueous solubility.
期刊介绍:
The European Journal of Medicinal Chemistry is a global journal that publishes studies on all aspects of medicinal chemistry. It provides a medium for publication of original papers and also welcomes critical review papers.
A typical paper would report on the organic synthesis, characterization and pharmacological evaluation of compounds. Other topics of interest are drug design, QSAR, molecular modeling, drug-receptor interactions, molecular aspects of drug metabolism, prodrug synthesis and drug targeting. The journal expects manuscripts to present the rational for a study, provide insight into the design of compounds or understanding of mechanism, or clarify the targets.