Repolarizing M2-like tumor associated macrophages (TAMs) into M1 phenotype by blocking CSF-1/CSF-1R signaling pathway represents a promising strategy to remodel the tumor immune microenvironment. Therefore, the discovery of novel potent CSF-1R inhibitors is of great significance for colorectal cancer immunotherapy. In this work, a series of novel CSF-1R inhibitors were designed and synthesized through rational molecular hybridization strategy and step by step structural optimization based on PLX3397 and BLZ945. Among these derivatives, compound