Synthesis and Molecular Docking Studies of Some Fluorinated 2-Aminopyrimidines, Pyrazoles and Isoxazoles as Possible Anti-cancer Agents

Abstract

The reaction of a-fluoro-oxoketene dithioacetals (2) with guanidinium nitrate, hydrazine hydrate, and hydroxyl amine hydrochloride in the presence of sodium ethoxide in ethanol under reflux conditions produced new series of fluorinated 2-aminopyrimidines, pyrazoles, and isoxazoles. In silico study was carried out to explore the binding potential of all the synthesized compounds toward the cancer target receptors (EGFR and IGF1R). It is worth noting that 4-fluoro-5- (methylthio)-3-(naphthalen-4-yl)isoxazole (5h) had a higher affinity for both targets. In particular, the synthesized compound showed crucial interatomic interactions with IGF1R along with two hydrogen bond interactions (LYS1030 and ASP1150). Further, experimental investigation of this molecule will be an interesting direction to take to develop a new anti-cancer agent.. KEYWORDS :Anti-cancer activity, Fluorinated 2-aminopyrimidines, Isoxazoles and Pyrazoles, Molecular Docking Studies.