Insilico Studies and Synthesis of New 2-Cycloproply Quinazoline Derivatives as Potential Anticancer Agents

The quinazoline scaffold is of significant importance in medicinal chemistry due to the diverse pharmacological activities of its derivatives, particularly their prominent role in cancer chemotherapy. In our continuous pursuit of novel anticancer pharmacophores, we aimed to synthesize a series of substituted quinazolines fused with substituted benzothiazoles and assess their in vitro anticancer potential. We commenced this endeavor by reacting anthranilic acid with cyclopropyl carbonyl chloride in the presence of 2,6-lutidine to yield an oxazine intermediate, which was subsequently converted into the targeted quinazoline derivatives. The subsequent reaction of these quinazolines with substituted isothiocyanatobenzene produced a series of novel compounds designed as potential inhibitors of EGF receptor tyrosine kinase. With a focus on the C-3 position of the quinazoline ring, we synthesized eleven diverse derivatives. These compounds underwent characterization and confirmation using IR, 1H NMR, 13C NMR, and mass spectrometry. All eleven synthesized compounds were submitted to the National Cancer Institute (NCI), USA, for in vitro anticancer screening, and seven of these were selected by the NCI for further evaluation against the full NCI 60 cell panel at a single high dose (10-5 M).