Design, Synthesis, Molecular Docking and Biological Activity of Pyrazolo[3,4-b]pyridines as Promising Lead Candidates AgainstMycobacterium tuberculosis

Abstract

AbstractPyrazolo[3,4-b]pyridine is a medicinally privileged structure. We have achieved a new and facile synthesis of a combinatorial library of its tetra- and persubstituted derivatives by trifluoracetic acid catalysed condensation of a group of 5-aminopyrazoles and a group of α-oxoketene dithioacetals. Furthermore, we demonstrated structural modification of the products via reductive desulfurization, hydrolysis of the ester and Suzuki coupling of the bromo derivative with aryl bornoic acids. Some of the products were subjected toin vitroMABA assay againstM. tuberclulosisH37Rv strain andin silicoanalysis by binding to pantothenate synthetase fromM. tuberclulosis(MTBPS). The results indicated that the pyazolo[3,4-b]pyridine with N(1)CH3, C(3)C6H5, C(4)pCH3C6H5, C(5)CO2Et, C(6)SMe substitutions exhibits promising antituberculotic activity.