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设计、合成和评价 2、6、8-取代咪唑并吡啶衍生物作为有效的 PI3K 抑制剂。

Design, synthesis and evaluation of 2, 6, 8-substituted Imidazopyridine derivatives as potent PI3K inhibitors.

机构信息

Guizhou Provincial Engineering Technology Research Center for Chemical Drug R&D, Guizhou Medical University, Guiyang, China.

Department of Pharmacy, Guizhou Provincial People's Hospital, Guiyang, China.

出版信息

J Enzyme Inhib Med Chem. 2023 Dec;38(1):2155638. doi: 10.1080/14756366.2022.2155638.

DOI:10.1080/14756366.2022.2155638
PMID:36650905
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9858543/
Abstract

Inhibition of PI3K pathway has become a desirable strategy for cancer treatment. In this work, a series of 2, 6, 8-substituted Imidazo[1,2-a]pyridine derivatives were designed and screened for their activities against PI3K and a panel of PI3K-addicted cancer cells. Among them, compound was identified as a PI3K inhibitor with nanomolar potency as well as acceptable antiproliferative activity. Flow cytometry analysis confirmed induced cell cycle arrest and apoptosis in T47D cells. In addition, it also showed desirable ADME properties. The design, synthesis, and SAR exploration of are described within.

摘要

抑制 PI3K 通路已成为癌症治疗的一种理想策略。在这项工作中，设计并筛选了一系列 2、6、8-取代的咪唑并[1,2-a]吡啶衍生物，以评估它们对 PI3K 和一系列依赖于 PI3K 的癌细胞的活性。其中，化合物 被鉴定为具有纳摩尔效力和可接受的抗增殖活性的 PI3K 抑制剂。流式细胞术分析证实 诱导了 T47D 细胞的细胞周期停滞和细胞凋亡。此外，它还表现出良好的 ADME 性质。本文描述了 的设计、合成和 SAR 探索。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a3e1/9858543/9fb47fec6f4f/IENZ_A_2155638_F0005_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a3e1/9858543/fdd5f90723e1/IENZ_A_2155638_F0001_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a3e1/9858543/ae95624878b2/IENZ_A_2155638_F0002_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a3e1/9858543/9be28e778354/IENZ_A_2155638_SCH0001_B.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a3e1/9858543/100ad1e193d3/IENZ_A_2155638_F0003_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a3e1/9858543/f302a8712c97/IENZ_A_2155638_F0004_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a3e1/9858543/9fb47fec6f4f/IENZ_A_2155638_F0005_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a3e1/9858543/fdd5f90723e1/IENZ_A_2155638_F0001_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a3e1/9858543/ae95624878b2/IENZ_A_2155638_F0002_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a3e1/9858543/9be28e778354/IENZ_A_2155638_SCH0001_B.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a3e1/9858543/100ad1e193d3/IENZ_A_2155638_F0003_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a3e1/9858543/f302a8712c97/IENZ_A_2155638_F0004_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a3e1/9858543/9fb47fec6f4f/IENZ_A_2155638_F0005_C.jpg

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