Synthesis of novel amide/amino acid functionalized pyrazolo[3,4‐b]pyridine derivatives; their anticancer activity and docking studies

Abstract

AbstractimageA series of novel pyrazolo[3,4‐b]pyridine amide/amino acid functionalized derivatives 5a–h, 6a–d, and 7a, 7b were synthesized, respectively, from 6‐thiophenyl‐4‐(trifluoromethyl)‐1H‐pyrazolo[3,4‐b]pyridin‐3‐amine 1. Compound 1 reacted with chloroacetamide in the presence of K2CO3 to form compound 2 (O‐tagged acetamide derivative), compound 2 on reaction with hydrazine hydrate in refluxing condition to afford cyclized pyrazolopyridine derivatives 3, compound 3 on reaction with bromoethyl acetate to get ester derivative of pyrazolopyridine 4, compound 4 on reaction with different primary amines and amino acids like (aliphatic amines, cyclic secondary amines, or L‐amino acids) under different set of conditions to obtain title compounds. All the final synthesized compounds 5a–h, 6a–d, and 7a, 7b were screened for anticancer activity against four cancer cell lines, such as ‘A549—Lung cancer (CCL‐185), MCF7—Breast cancer (HTB‐22), DU145—Prostate cancer (HTB‐81), and HeLa—Cervical cancer(CCL‐2)’ promising 5c, 5e, and 5h compounds have been identified. For compounds 5c, 5e, and 5h molecular docking interactions have been identified.