Sustainable synthesis of nitrogen rich pyridazine-triazole scaffolds as efficient Tyrosine kinase inhibitors via Click reaction
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2025
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The Cu-catalyzed click reaction was employed to furnish 1H-1,2,3-triazoles from substituted phenylacetylenes and 6-azido-3-nitroimidazo[1,2-b]pyridazine through which the resulting 3-nitroimidazo[1,2-b]pyridazine-triazoles (4a-4k) achieved in yields between 82‐98 %. In silico approach identified compounds as the most promising candidates to assess their tyrosine kinase inhibition capabilities. The target compounds with bromo, hydroxy, acetyl and methyl groups at para positions were subjected for In vitro assessments according to their Tyrosine Kinase (TK) enzyme binding affinity. All synthesized compounds fulfilled the criteria for drug likeness according to their ADMET profile assessment. The investigated compounds demonstrated medium-level to good activity against multiple TK enzymes; specifically, compounds with acetyl substitution demonstrated lower IC50 values, whereas hydroxy-substituted compounds presented higher IC50 values across all tested TK enzymes. DFT investigations demonstrated that acetyl substituted molecules react strongly with lower stability and a significant dipole moment (10.16 Debye) followed by methyl substituted.
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P. Sridhar, Harshil Bhatt, Kishor Padala, Sabbasani Rajasekhara Reddy, Manikandan Alagumuthu, Sivakumar Arumugam, Lin Chun-Cheng, Sheng-kai Wang, Sustainable synthesis of nitrogen rich pyridazine-triazole scaffolds as efficient Tyrosine kinase inhibitors via Click reaction, Bioorganic Chemistry, Volume 161, 2025, 108553, ISSN 0045-2068, https://doi.org/10.1016/j.bioorg.2025.108553.