An Efficient Approach for the Synthesis and Antitumor Evaluation of Novel Azo- and Anil-Linked with 3-Aminopyrazolo[3,4-b]pyridine.

Abstract

In this project, an effective procedure for constructing a new combination of pyrazolo[3,4-b]pyridine was depicted through the coupling of diazonium salt 2 of heterocyclic amine 1 with active methylene, enamine, and amidine moieties such as 3, 5, 7, and 9 at 0-5 °C in pyridine to afford hydrazinylhydrazonoyl derivatives 4, and diazenylheterocyclic derivatives 6, 8, and 10, respectively. Also, aminopyrazolo[3,4-b]pyridine 1 condensed with different aryl or heteroaryl aldehydes in EtOH/AcOH gave the corresponding aldimine 14, 15, 16. Compound 15 was cyclized via refluxing in DMF for 6 h to afford 18, while the transformation of compound 16 with an alkyl halide afforded 19a, b. The synthesized compounds, explicated by spectral data and elemental analysis, were examined for their antitumor activities. The in vitro cytotoxic activity of new pyrazolo[3,4-b]pyridines against the A2780CP, MCF-7, and HepG-2 cell lines was evaluated using the reference doxorubicin. Compounds 15 and 19a exhibited high reactivity against the A2780CP cell lines, with IC50 values of 35 and 17.9 μM, respectively. Also, compound 28 had the cytotoxic potential for A2780CP and MCF-7 cell lines, with IC50 values of 14.5, and 27.8 μM, respectively.