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具有抗癌活性的新型稠合吡咯并二氮杂卓类化合物库的合成。

Synthesis of a novel fused pyrrolodiazepine-based library with anti-cancer activity.

作者信息

Malik Neha, Iyamu Iredia D, Scheidt Karl A, Schiltz Gary E

机构信息

Center for Molecular Innovation and Drug Discovery, Northwestern University, Evanston, Illinois, 60208, United States.

Department of Chemistry, Northwestern University, Evanston, Illinois, 60208, United States.

出版信息

Tetrahedron Lett. 2018 Apr 11;59(15):1513-1516. doi: 10.1016/j.tetlet.2018.03.021. Epub 2018 Mar 8.

DOI:10.1016/j.tetlet.2018.03.021
PMID:29610541
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5877814/
Abstract

Development of drugs for new and persistent diseases will increasingly rely on the expansion of accessible chemical space to allow exploration of novel molecular targets. Here we report the synthesis of a library of novel fused heterobicyclic small molecules based on the 1,4-diazepine and 2,4-pyrrolidinedione scaffolds. Key chemical transformations included a Mannich-type condensation and chemoselective N-acylation reactions. Screening shows anti-cancer activity of several library compounds which suggests translational potential of this novel chemical scaffold.

摘要

针对新型和持续性疾病的药物研发将越来越依赖于可及化学空间的拓展，以便探索新的分子靶点。在此，我们报告了基于1,4 - 二氮杂卓和2,4 - 吡咯烷二酮支架的新型稠合杂双环小分子文库的合成。关键的化学转化包括曼尼希型缩合反应和化学选择性N - 酰化反应。筛选结果显示文库中的几种化合物具有抗癌活性，这表明这种新型化学支架具有转化应用潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa71/5877814/6bc8f5f95dee/nihms952811f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa71/5877814/464a8d9ae317/nihms952811f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa71/5877814/b9cd4128b1e0/nihms952811f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa71/5877814/6d8c1c617f3c/nihms952811f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa71/5877814/6bc8f5f95dee/nihms952811f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa71/5877814/464a8d9ae317/nihms952811f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa71/5877814/b9cd4128b1e0/nihms952811f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa71/5877814/6d8c1c617f3c/nihms952811f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa71/5877814/6bc8f5f95dee/nihms952811f4.jpg

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本文引用的文献

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