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新型吡非尼酮衍生物作为抗纤维化药物的合成与评价

Synthesis and evaluation of new pirfenidone derivatives as anti-fibrosis agents.

作者信息

Gu Chenxi, Li Wei, Ju Qing, Yao Han, Yang Lisheng, An Baijiao, Hu Wenhao, Li Xingshu

机构信息

School of Pharmaceutical Sciences, Sun Yat-Sen University Guangzhou 510006 PR China

Medicine and Pharmacy Research Center, Binzhou Medical University Yantai Shandong Province 264003 PR China.

出版信息

RSC Adv. 2022 May 13;12(23):14492-14501. doi: 10.1039/d2ra00990k. eCollection 2022 May 12.

DOI:10.1039/d2ra00990k
PMID:35702193
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9102048/
Abstract

Two series of new pirfenidone derivatives, in which phenyl groups or benzyl groups are attached to the nitrogen atom of the pyridin-2(1)-one moiety were synthesized and evaluated as anti-fibrosis agents. Among them, compound 5d, with a ()-2-(dimethylamino) propanamido group in the R position (series 1) exhibited 10 times the anti-fibrosis activity (IC: 0.245 mM) of pirfenidone (IC: 2.75 mM). Compound 9d (series 2) gave an IC of 0.035 mM against the human fibroblast cell line HFL1. The mechanism of the optimal compound inhibiting fibrosis was also studied.

摘要

合成了两系列新的吡非尼酮衍生物，其中苯基或苄基连接到吡啶-2(1)-酮部分的氮原子上，并作为抗纤维化剂进行了评估。其中，在R位带有()-2-(二甲基氨基)丙酰胺基的化合物5d（系列1）表现出比吡非尼酮（IC：2.75 mM）高10倍的抗纤维化活性（IC：0.245 mM）。化合物9d（系列2）对人成纤维细胞系HFL1的IC为0.035 mM。还研究了最佳化合物抑制纤维化的机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7eb0/9102048/130d650fcb6c/d2ra00990k-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7eb0/9102048/3c9e9c0a6f9b/d2ra00990k-s1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7eb0/9102048/55db8b3674ca/d2ra00990k-s2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7eb0/9102048/04151f153954/d2ra00990k-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7eb0/9102048/c880eddb2b63/d2ra00990k-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7eb0/9102048/836533fd13b7/d2ra00990k-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7eb0/9102048/8428272afdaf/d2ra00990k-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7eb0/9102048/130d650fcb6c/d2ra00990k-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7eb0/9102048/3c9e9c0a6f9b/d2ra00990k-s1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7eb0/9102048/55db8b3674ca/d2ra00990k-s2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7eb0/9102048/04151f153954/d2ra00990k-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7eb0/9102048/c880eddb2b63/d2ra00990k-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7eb0/9102048/836533fd13b7/d2ra00990k-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7eb0/9102048/8428272afdaf/d2ra00990k-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7eb0/9102048/130d650fcb6c/d2ra00990k-f5.jpg

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