Synthesis of New Conjugates 1H‑Pyrazolo[3,4-b]pyridine-phosphoramidate and Evaluation against Leishmania amazonensis

Abstract

In this research three series of substituted 1H-pyrazolo[3,4-b]pyridine phosphoramidates were synthesized and characterized by infrared, 1 H, 13 C, and 31 P nuclear magnetic resonance (NMR) spectroscopy and high-resolution mass spectrometry. The products were obtained in good yields (67-83%) under mild conditions by nucleophilic aromatic substitution reaction of aminoalkylphosphoramidates over 4-chloro-1H-pyrazolo[3,4-b]pyridines. These compounds were evaluated as antileishmanials against Leishmania amazonensis promastigotes in vitro. Among all, compounds of a series showed expressive antileishmanial activity. Two of them emerged as the most active, with IC 50 values of 6.44 ± 1.49 and 12.25 ± 0.68 µM. The cytotoxicity of this series was assessed on murine cells and presented values similar to the reference drug pentamidine.