Saturated bioisosteres of substituted benzenes offer opportunities to fine-tune the properties of drug candidates in development. Bioisosteres of -benzenes, such as those based on bicyclo[1.1.1]pentane, are now very common and can be used to increase aqueous solubility and improve metabolic stability, among other benefits. Bioisosteres of - and -benzenes were for a long time severely underdeveloped by comparison. This has begun to change in recent years, with a number of potential systems being reported that can act as bioisosteres for these important fragments. In this review, we will discuss these recent developments, summarizing the synthetic approaches to the different bioisosteres as well as the impact they have on the physiochemical and biological properties of pharmaceuticals and agrochemicals.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11035989 | PMC |
| http://dx.doi.org/10.3762/bjoc.20.78 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Modular access to saturated bioisosteres of anilines via photoelectrochemical decarboxylative C(sp)-N coupling.
Nat Commun
January 2025
Frontiers Science Center for Transformative Molecules, School of Chemistry and Chemical Engineering, Zhangjiang Institute for Advanced Study, Shanghai Jiao Tong University, Shanghai, 200240, China.
In drug development, the substitution of benzene rings in aniline-based drug candidates with saturated bridged bicyclic ring systems often enhances pharmacokinetic properties while preserving biological activity. However, current efforts predominantly focuses on bicyclo[1.1.
View Article and Find Full Text PDFRecent Advances in Radical Coupling Reactions Directly Involving Bicyclo[1.1.1]pentane (BCP).
Top Curr Chem (Cham)
January 2025
School of Pharmacy, Hangzhou Normal University, Hangzhou, 311121, Zhejiang, People's Republic of China.
BCP (bicyclo[1.1.1]pentane) is an ideal saturated carbon bioisostere, instead of the traditional benzene group, which has been extensively developed.
View Article and Find Full Text PDFLight-enabled scalable synthesis of bicyclo[1.1.1]pentane halides and their functionalizations.
Nat Synth
September 2024
Enamine Ltd., Kyiv, Ukraine.
In 2012, bicyclo[1.1.1]pentanes were demonstrated to be bioisosteres of the benzene ring.
View Article and Find Full Text PDFCatalytic Intermolecular Asymmetric [2π + 2σ] Cycloadditions of Bicyclo[1.1.0]butanes: Practical Synthesis of Enantioenriched Highly Substituted Bicyclo[2.1.1]hexanes.
J Am Chem Soc
December 2024
State Key Laboratory of Chemical Oncogenomics, Institute of Biopharmaceutics and Health Engineering, Tsinghua Shenzhen International Graduate School, Shenzhen 518055, China.
The high percentage of sp-hybridized carbons and the presence of chiral carbon centers could contribute to increased molecular complexity, enhancing the likelihood of clinical success of drug candidates. Three-dimensional (3D) bridged motifs have recently garnered significant interest in medicinal chemistry. Bicyclo[2.
View Article and Find Full Text PDFRing Expansion toward Fused Diazabicyclo[3.1.1]heptanes through Lewis Acid Catalyzed Highly Selective C-C/C-N Bond Cross-Exchange Reaction between Bicyclobutanes and Diaziridines.
Angew Chem Int Ed Engl
January 2025
State Key Laboratory of Chemo/Biosensing and Chemometrics, Advanced Catalytic Engineering Research Center of the Ministry of Education, College of Chemistry and Chemical Engineering, Hunan University, 410082, Changsha, Hunan, P. R. China.
Article Synopsis
- Bicyclic scaffolds are important in drug discovery due to their ability to resemble benzene structures.
- This study presents a novel method using a Lewis acid catalyst to facilitate a reaction between bicyclobutanes and diaziridines, yielding valuable azabicyclo[3.1.1]heptane compounds with high efficiency.
- The research also successfully scaled up the process and introduced a chiral zinc-based catalyst to promote enantioselective synthesis, achieving significant optical purity.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!