The development of HEC-866 and its analogues for the treatment of idiopathic pulmonary fibrosis.
Lin R, Zhang Z, Cao S, Yang W, Zuo Y, Yang X, Zhang J, Xu J, Li J, Wang X.
Idiopathic pulmonary fibrosis (IPF) is a chronic progressive lung disease with a typical survival time between three to five years. Two drugs, pirfenidone and nintedanib have been approved for the treatment of IPF, but they have limited efficacy. Thus, the development of new drugs to treat IPF is an urgent medical need. In this paper we report the discovery of a series of orally active pyrimidin-4(3<i>H</i>)-one analogs which exhibit potent activity in <i>in vitro</i> assays. Among them, HEC-866 showed promising efficacy in rat IPF models. Since HEC-866 also had good oral bioavailability, a long half-life and favorable long-term safety profiles, it was selected for further clinical evaluation.