Synthesis, spectroscopic characterization, structural studies, thermal analysis and molecular docking of N-(2-methyl-5-nitrophenyl)-4-(pyridin-2-yl)pyrimidin-2-amine, a precursor for drug design against chronic myeloid leukemia.

The synthesis, crystal structure and spectroscopic and electronic properties of N-(2-methyl-5-nitro­phen­yl)-4-(pyridin-2-yl)pyrimidin-2-amine (NPPA), C16H13N5O2, a potential template for drug design against chronic myelogenous leukemia (CML), is reported. The design and construction of the target mol­ecule were carried out starting from the guanidinium nitrate salt (previously synthesized) and the corresponding enaminone. X-ray diffraction analysis and a study of the Hirshfeld surfaces revealed important inter­actions between the nitro-group O atoms and the H atoms of the pyridine and pyrimidine rings. A crystalline ordering in layers, by the stacking of rings through inter­actions of the π–π type, was observed and confirmed by a study of the shape-index surfaces and dispersion energy calculations. Qu­anti­tative electrostatic potential studies revealed the most positive value of the mol­ecule on regions close to the N—H groups (34.8 kcal mol−1); nevertheless, steric impediments and the planarity of the mol­ecule do not allow the formation of hydrogen bonds from this group. This inter­action is however activated when the mol­ecule takes on a new extended conformation in the active pocket of the enzyme kinase (PDB ID 2hyy), inter­acting with protein residues that are fundamental in the inhibition process of CML. The most negative values of the mol­ecule are seen in regions close to the nitro group (−35.4 and −34.0 kcal mol−1). A mol­ecular docking study revealed an energy affinity of ΔG = −10.3 kcal mol−1 for NPPA which, despite not having a more negative value than the control mol­ecule (Imatinib; ΔG = −12.8 kcal mol−1), shows great potential to be used as a template for new drugs against CML.