Background: Zika virus (ZIKV) remains an important cause of congenital infection, fetal microcephaly, and Guillain-Barré syndrome in the population. In 2016, WHO declared a cluster of microcephaly cases and other neurological disorders reported as a global public health emergency in Brazil. There is still no specific treatment for Zika virus fever, only palliative care. Therefore, there is a need for new therapies against this disease. According to the literature, thiosemicarbazone, phthalimide and thiazole are privileged structures with several biological activities, including antiviral activity against various viruses. Objective: Based on this, this work presents an antiviral screening using previously synthesized compounds derived from thiosemicarbazone, phthalimide, and thiazole as new hits active against ZIKV. Methods: After synthesis and characterization, all compounds were submitted to Cytotoxicity by MTT and Antiviral activity against ZIKV assays. Results: Compounds 63, 64, 65, and 73 exhibited major reductions in the ZIKV title from this evaluation. Compounds 63 (99.74%), 64 (99.77%), 65 (99.92%), and 73 (99.21%) showed a higher inhibition than the standard 6MMPr (98.74%) at the CC20 dose. These results revealed new chemical entities with anti-ZIKV activity. Conclusion: These derivatives are promising candidates for further assays. In addition, the current approach brings a new privileged scaffolding, which may drive future drug discovery for ZIKV.