2‐(1‐Methyl‐1H‐indazol‐5‐yl)‐N‐arylisonicotinamide Analogs: Synthesis, Anticancer Screening, SAR and ADMET Studies

Abstract

In this current research framework, we detailed the synthesis of ten novel 2‐(1‐methyl‐1H‐indazol‐5‐yl)‐N‐arylisonicotinamide analogs (3a–j). The synthesis of these compounds (3a–j) involved a three‐step process, employing the Suzuki‐Miyaura coupling reaction, which successfully linked 1‐methyl‐1H‐indazole with isonicotinamide to satisfactory yields. The synthesized compounds were characterized using various spectroscopic techniques. To assess their potential, the anticancer activity of compounds (3a–j) was evaluated following the National Cancer Institute (NCI US) protocol against nine panels comprising different cancer cell lines, at a concentration of 10−5 M. Growth percentage (GP) and percentage growth inhibition (PGI) were calculated for each compound. Notably, the CNS cancer cell line SNB‐75 exhibited a remarkable PGI of 99.16 percent, indicating high sensitivity to the tested compound 3e. Additionally, ADMET prediction suggested that most of the synthesized compounds possess drug‐like properties, with low adverse effects and toxicity. These findings represent a significant advancement, offering potential avenues for further developments in the field of cancer research.