biostudies-literatureGu CNatural Science Foundation of Shandong Province14492-14501https://www.ebi.ac.uk/biostudies/studies/S-EPMC9102048biostudies-literatureUnknown12(23)Two series of new pirfenidone derivatives, in which phenyl groups or benzyl groups are attached to the nitrogen atom of the pyridin-2(1<i>H</i>)-one moiety were synthesized and evaluated as anti-fibrosis agents. Among them, compound 5d, with a (<i>S</i>)-2-(dimethylamino) propanamido group in the R₂ position (series 1) exhibited 10 times the anti-fibrosis activity (IC₅₀: 0.245 mM) of pirfenidone (IC₅₀: 2.75 mM). Compound 9d (series 2) gave an IC₅₀ of 0.035 mM against the human fibroblast cell line HFL1. The mechanism of the optimal compound inhibiting fibrosis was also studied.RSC advancesSynthesis and evaluation of new pirfenidone derivatives as anti-fibrosis agents.PMC9102048ZR2021QB172Li WAn BLi XGu CYang LHu WYao HJu QfalseSynthesis and evaluation of new pirfenidone derivatives as anti-fibrosis agents.Two series of new pirfenidone derivatives, in which phenyl groups or benzyl groups are attached to the nitrogen atom of the pyridin-2(1<i>H</i>)-one moiety were synthesized and evaluated as anti-fibrosis agents. Among them, compound 5d, with a (<i>S</i>)-2-(dimethylamino) propanamido group in the R₂ position (series 1) exhibited 10 times the anti-fibrosis activity (IC₅₀: 0.245 mM) of pirfenidone (IC₅₀: 2.75 mM). Compound 9d (series 2) gave an IC₅₀ of 0.035 mM against the human fibroblast cell line HFL1. The mechanism of the optimal compound inhibiting fibrosis was also studied.2022-01-01T00:00:00Z2022 May2026-05-10T01:39:54.513Z2025-02-19T01:12:36.896ZS-EPMC91020483570219310.1039/d2ra00990k