Synthesis and antitumor activity of novel 2-(1-substituted- piperidin-4-ylamino)quinazolines as antitumor agents

A variety of novel 2-(1-substituted-piperidine-4-ylamino)quinazoline derivatives were prepared and their antiproliferative activities on five cancer cell lines were evaluated by MTT assay.  Quinazolines 4j−4l, 5a, 5b and 5d bearing a small hydrophobic alkyl group on piperidine ring exhibited potent antitumor activities with IC₅₀ values at micromolar level.  Compound 4l displayed significant in vivo antitumor activity with 72.9% inhibition on H22 tumor growth and 80% inhibition on Lewis lung cancer growth at a dose of 200 mg·kg⁻¹.