The goal of this work was to synthesize new substituted 2-aminoquinoline-3-carboxamide derivatives from substituted anilines utilizing the Vilsmeier-Haack reaction, and then to test these compounds for in vitro anticancer activity and molecular docking in order to identify prospective lead molecules. Substituted aniline, acetanilide, 2-chloro-3-carbaldehyde to carboxylic acid as well as coupling provide the lead compounds and were characterized by physical and spectral methods. In vitro cytotoxicity testing was done by using MTT assay method. Research on the binding interaction of the most effective drugs was conducted using AutoDock molecular docking tool. Novel Series of substituted 2-aminoquinoline-3-carboxamide derivatives have been synthesized as well as verified utilizing different spectral methods for example mass spectrometry, carbon-13 nuclear magnetic resonance, nuclear magnetic resonance, and infra-red. In a cytotoxicity testing vs a breast cancer cell line, synthesized compounds showed some potential (MCF-7). Four derivatives 6b, 6c, 6j, and 6o were shown to have more efficacy than Sunitinib in an in vitro cytotoxicity assessment research. Moreover compounds 6b, 6c, 6j, and 6o exhibited higher binding score at platelet-derived growth factor receptor active sites (PDB: 5GRN) compared with standard sunitinib. This article described the synthesis of sixteen novel substituted aniline results in substituted 2-aminoquinoline-3-carboxamide derivatives. The results showed that compounds 6b, 6c, 6j, and 6o exhibited promising anticancer activity. Sunitinib is currently the only approved inhibitor of PDGFR; however the 2-aminoquinoline-3-carboxamides showed promise as a more selective alternative. The above findings were also supported by molecular docking studies.These findings may serve as models for future research and derivatization, opening the door to the development of effective and precise PDGFR inhibitors.