The Rab23 protein overexpression has a well-validated role in variety of human cancers. Therefore, the present research aimed to identify new Rab23 protein inhibitor candidates using computational based drug design methodology. A novel series of chromeno[2,3-b] pyridine derivatives has been synthesized by the cyclocondensation of 2-amino-3-cyano-4H-chromenes with cyclohexanone and cyclopentanone in ethanolicpiperidine solution. The 2-amino-4H-chromenes were obtained using one pot multicomponent condensation of resorcinol, malononitrile and aromatic aldehydes in the presence in ethanolicpiperidine solution. All newly synthetic compounds were characterized by spectral analysis IR, NMR and MS and elemental analysis techniques. The best binding modes of chromene derivatives were evaluated via molecular docking studies and binding energy calculations, using PyRx tool. The study has shown that the pyran and pyridine moieties interact favorably with the binding site of target protein, providing the mechanism of action against human sapiens Rab23 protein.