A green tandem cyclization approach to substituted 2-aminothiazoles via molecular sieve/I2 catalysis: DFT, molecular dockings, and pharmacokinetic profiles

Abstract

In an effort to promote eco-friendly organic synthesis, a facile, sustainable, and highly efficient procedure for the synthesis of 2-amino-1,3-thiazole derivatives was developed. The protocol of this process incorporates the principles of green chemistry. Moreover, the NMR, FT-IR, and UV simulations of the compounds were conducted at the B3LYP/6-311++G** level for comparison with the observed counterparts. FMO analyses revealed that the PhTA compound exhibited the highest stability via back-donation; among the compounds, NapTA exhibited the lowest stability via back-donation. Furthermore, the –NH₂ group did not influence electrophilic attacks because the LUMO for all compounds did not separate from this group. Also, the lipophilicity, solubility, pharmacokinetics, and drug-likeness profiles of the compounds were evaluated. The BOILED-Egg model implied that the compounds PhTA, BFTA, and NapTA permeate through the BBB (blood–brain-barrier) passively, while the FTA and ThTA compounds have no potency in terms of BBB penetration. Also, all compounds met the requested physicochemical criteria according to the Lipinski, Veber, and Egan rules. Additionally, the molecules were analyzed using the molecular docking method to gain insights into their possible anticancer activity. Vascular endothelial growth factor receptor-2, human estrogen receptor, human cytochrome P450, and human extracellular signal-regulated kinase 2 were selected. All the obtained results are expected to provide important insights into the structure–reactivity relationship in early-stage drug design research.