SBA-Pr-SO۳H catalyzed synthesis, and molecular docking study of aryltetrahydrodipyrazolopyridine derivatives as PDK۱ inhibitors

Hantzsch reaction is a popular procedure for the synthesis of dihydropyridines (DHPs) through the reaction of two equivalents of a β-ketoester with one equivalent of aldehyde in the presence of an ammonia source. The Hantzsch reaction of pyrazolone, aromatic aldehydes and ammonium acetate was studied in the presence of SBA-Pr-SO۳H, as the catalyst, to gain tetrahydrodipyrazolopyridines. The high yield of products (۸۰-۹۵%) within a short reaction time (۶-۱۵ min) proves the efficiency of this methodology. Finally, molecular docking studies were used to show the binding mode of these compounds in the active site of ۳-phosphoinositide-dependent kinase ۱ (۵OOT). Docking computations show the Gold Score value and the binding mode of resulting complexes. The synthesized compounds can bind to the receptor’s residues by forming hydrogen bonds and π interactions. The detailed analysis of the binding mode of the best-docked molecule exhibited a hydrogen bond between NH substituent and Tyr۲۰. Moreover, π-π and π-cation interactions can be seen with the residues Tyr۲۰ and Lys۳۸, respectively.