This investigation focuses on the design, synthesis, comprehensive analysis, and binding affinity with the epidermal growth factor receptor (EGFR), Cyclin-Dependent Kinase 6 (CDK6) of a new 1,8-naphthyridine-pivalamide hybrid 1. The newly synthesised 1,8-naphthyridine-pivalamide hybrid 1 was characterised by FT-IR, 1 H NMR, elemental analysis, and single-crystal X-ray analysis. The crystal structure analysis disclosed that 1 is hydrated and supramolecular assembly is stabilized via O-H⋯N, N-H⋯O, and O-H⋯O and off-set 𝜋⋯𝜋 contacts. Various types of non-covalent contacts existing in the 1,8-naphthyridine-pivalamide hybrid 1 is explored, and subsequently quantified employing Hirshfeld surface analysis and 2D fingerprint plots. Furthermore, void study was utilised to examine the mechanical stability and presence of the cavity within the solid-state structure of 1. The interaction energies between molecules in 1 have been investigated using the interaction energy calculation. Geometric parameters of the optimized structure of 1 was determined utilizing the DFT calculations. Furthermore, molecular docking studies indicated that the 1,8-naphthyridine-pivalamide hybrid 1 demonstrated promising binding affinity with EGFR and CDK6, compared to their known inhibitors. The newly synthesized 1,8-naphthyridine-pivalamide hybrid 1 also exhibited drug-likeness as predicted by SwissADME.
Saha et al. (2026) studied this question.