Aiming to develop novel tropomyosin receptor kinase A (TrkA) inhibitors, a scaffold hopping strategy was utilized by transforming the fused indazole of Entrectinib to phenyl triazole/thiazole skeleton to obtain compounds 7a-7 h and 13a-13 h. In the light of MTT assay, phenyl triazole derivatives 7a-7 h exhibited moderate anti-proliferative activities against KM-12 cells with the IC₅₀ values of 1.78–17.51 μM, while phenyl thiazole derivatives 13a-13 h showed the weaker efficacy. Further structure-guided optimizations by combining the phenyl triazole skeleton with 3,5‑difluorophenyl and 3-carbamoyl-4-piperazinylaniline moiety led to compounds 19a-19d and 20. Eventually, 19c bearing (2-(4-methylpiperazin-1-yl)phenyl)(morpholino)methanone moiety exhibited excellent anti-proliferative activity on TrkA-positive KM-12 cells with IC₅₀ value of 0.17 μM. Meanwhile, compound 19c showed the inhibitory potency on TrkA with IC₅₀ value of 1.6 nM, and displayed higher selectivity on TrkA over TrkB (IC₅₀ = 12.3 nM) and TrkC (IC₅₀ = 18.4 nM). The dedicated wound healing and colony formation assay indicated that the optimal compound 19c could suppress migration and significantly inhibit KM-12 cell colony formation in a dose-dependent manner. In addition, 19c could weakly induce apoptosis of KM-12 cell in immunofluorescent staining analysis. Taken together, the above results suggest 19c as a novel TrkA inhibitor worthy of further profiling.