Styrylquinoline analogs exhibiting antiproliferative activity against glioblastoma multiforme were tested for tyrosine kinase inhibition. A preliminary SAR analysis based on previous results showed that the styrylquinoline fragment is a promising privileged structure. The addition of appropriate pharmacophores to both the quinoline structure and the benzene ring, which was attached to the 2-position, significantly altered the antiproliferative properties. Namely, OH or NO2 substituents had a positive effect on activity, while F and OAc molecular fragments had a negative impact. Screening conducted on a panel of receptor tyrosine kinases revealed the high potential of the tested compounds for use as IGF1R inhibitors. Molecular docking performed on the IGF1R unphosphorylated inactive conformation confirmed the high binding affinity of the active styrylquinoline derivatives.