SBA-Pr-SO3H catalyzed synthesis, and molecular docking study of aryltetrahydrodipyrazolopyridine derivatives as PDK1 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-SO3H, as the catalyst, to gain tetrahydrodipyrazolopyridines. The high yield of products (80-95%) within a short reaction time (6-15 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 3-phosphoinositide-dependent kinase 1 (5OOT). 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 Tyr20. Moreover, π-π and π-cation interactions can be seen with the residues Tyr20 and Lys38, respectively.

SBA-Pr-SO3H catalyzed synthesis, and molecular docking study of aryltetrahydrodipyrazolopyridine derivatives as PDK1 inhibitors Keywords:

Hantzsch reaction , SBA-Pr-SO3H , Pyrazolone , Tetrahydrodipyrazolopyridines , Molecular docking