•Five novel 4-aminopyridine derivatives were designed, synthesized, and evaluated.•Compounds 2 and 3 showed strong cell viability and low cytotoxicity.•Compound 2 displayed obvious activity on anti-inflammation.•Compound 5 showed considerable inhibition of cell apoptosis.•Compound 3 showed anti-oxidation and positive inhibition of Rho kinase.Neuroprotection refers to the relative preservation of neuronal structure and function. Neuroprotective agents refer to substances that are capable of preserving brain function and structure. Currently, there are no neuroprotective agents available that can effectively relieve the progression of Parkinson’s disease. In this work, five novel 4-aminopyridine derivatives, including three amides and two ureas, were designed, synthesized, and evaluated using the rat PC12 mice pheochromocytoma cell line as an in vitro model. As well as human Rho kinase inhibitory experiment was performed. Among them, compound 3, which exhibited high cell viability, low cytotoxicity and good efficacy of inhibition on α-synuclein, oxidation, inflammation and Rho kinase, was profound as potential agents for Parkinson’s disease (PD).Download high-res image (52KB)Download full-size image