Synthesis and Docking Studies of Novel Bis(2-(Substituted(methyl)amino)-4-phenylthiazol-5-yl)methanone

Abstract

A new series of novel synthesis of bis(2-(substituted(methyl)amino)-4-phenylthiazol-5-yl)methanone (PVS 1-9) is reported. The carbonyl isothiocyanate (3) was synthesized by a para-cleavage of C–Cl bond of benzoyl chloride (1) with ammonium thiocyanate (2). The presence of carbonyl group in acyl isothiocyanates enhance the reactivity of acyl isothiocyanates upon reaction with substituted secondary amine (4) give n-alkylated adduct (5), which upon the reaction with dichloro acetone give target compound 7. Substituted derivatives as inhibitors against lungs, breast and EJFR assist cancer based on virtual screening cellular evaluations with NSCLC H1975 harboring EGFR L858R/T790M double mutations indicated that the most active compound PVS-7 could inhibit the proliferation of two cell lines in one digital micromolar scale. The enzymatically results indicated that compounds PVS-2, PVS-4 and PVS-9 were the most active inhibitor against EGFR T790M and above cancer activity with a ~82%. All compounds were well characterized by spectroscopic techniques and their purity was confirmed by UV-HPLC.