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氮杂螺环三酮类支架的重塑可实现具有不同表型效应的多样化 sp 丰富化合物的合成。

Scaffold Remodelling of Diazaspirotricycles Enables Synthesis of Diverse sp -Rich Compounds With Distinct Phenotypic Effects.

机构信息

School of Chemistry, University of Leeds, Leeds, LS2 9JT, UK.

Max-Planck Institute of Molecular Physiology, Department of Chemical Biology, Otto-Hahn-Strasse 11, Dortmund, 44227, Germany.

出版信息

Chemistry. 2023 May 8;29(26):e202203992. doi: 10.1002/chem.202203992. Epub 2023 Mar 22.

DOI:10.1002/chem.202203992
PMID:36722618
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10946999/
Abstract

A 'top down' scaffold remodelling approach to library synthesis was applied to spirotricyclic ureas prepared by a complexity-generating oxidative dearomatisation. Eighteen structurally-distinct, sp -rich scaffolds were accessed from the parent tricycle through ring addition, cleavage and expansion strategies. Biological screening of a small compound library based on these scaffolds using the cell-painting assay demonstrated distinctive phenotypic responses engendered by different library members, illustrating the functional as well as structural diversity of the compounds.

摘要

采用“自上而下”的支架重塑方法合成螺环三嗪脲，由生成复杂性的氧化去芳构化反应制备。通过环加成、断裂和扩展策略，从母体三环中获得了十八个结构不同的富 sp 支架。基于这些支架的小分子文库的细胞染色测定法的生物学筛选显示，不同文库成员引起的表型反应具有独特性，说明了化合物的功能和结构多样性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ef67/10946999/38a92783e4bb/CHEM-29-0-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ef67/10946999/44c0c663b61b/CHEM-29-0-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ef67/10946999/8880673ecedc/CHEM-29-0-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ef67/10946999/75bd5ca876f9/CHEM-29-0-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ef67/10946999/8ab119582b34/CHEM-29-0-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ef67/10946999/12047f46e566/CHEM-29-0-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ef67/10946999/772f48dc4a82/CHEM-29-0-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ef67/10946999/38a92783e4bb/CHEM-29-0-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ef67/10946999/44c0c663b61b/CHEM-29-0-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ef67/10946999/8880673ecedc/CHEM-29-0-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ef67/10946999/75bd5ca876f9/CHEM-29-0-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ef67/10946999/8ab119582b34/CHEM-29-0-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ef67/10946999/12047f46e566/CHEM-29-0-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ef67/10946999/772f48dc4a82/CHEM-29-0-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ef67/10946999/38a92783e4bb/CHEM-29-0-g006.jpg

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