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

ABSTRACT

Two series of new pirfenidone derivatives, in which phenyl groups or benzyl groups are attached to the nitrogen atom of the pyridin-2(1H)-one moiety were synthesized and evaluated as anti-fibrosis agents. Among them, compound 5d, with a (S)-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.