Discovery of 4-cyclopropyl-3-(2-((1-cyclopropyl-1-pyrazol-4-yl) amino) quinazolin-6-yl)--(3-(trifluoromethyl) phenyl) benzamides as potent discoidin domain receptor inhibitors for the treatment of idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a chronic fatal lung disease with a median survival time of 3-5 years. Inaccurate diagnosis, limited clinical therapy and high mortality together indicate that the development of effective therapeutics for IPF is an urgent need. In recent years, it was reported that DDRs are potential targets in anti-fibrosis treatment. Based on previous work we carried out further structure modifications and led to a more selective inhibitor by averting some fibrosis-unrelated kinases, such as RET, AXL and ALK. Extensive profiling of compound has demonstrated that it has potent DDR1/2 inhibitory activities, low toxicity, good pharmacokinetic properties and reliable anti-fibrosis efficacy. Therefore, we confirmed that discoidin domain receptors are promising drug targets for IPF, and compound would be a promising candidate for further drug development.