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.

Synthesis, spectroscopic (FT-IR and UV-Vis), crystallographic and theoretical studies, and a molecular docking simulation of an imatinib-like template.

The aim of the present study was to report the crystal structure and spectroscopic, electronic, supramolecular and electrostatic properties of a new polymorph of 4-(pyridin-2-yl)pyrimidin-2-amine (C9H8N4). The compound was synthesized under microwave irradiation. The single-crystal X-ray structure analysis revealed an angle of 13.36 (8)° between the planes of the rings, as well as molecules linked by Nsp2-H...N hydrogen bonds forming dimers along the crystal. The material was analyzed by FT-IR vibrational spectroscopy, while a computational approach was used to elucidate the vibrational frequency couplings. The existence of Nsp2-H...N hydrogen bonds in the crystal was confirmed spectroscopically by the IR peaks from the N-H stretching vibration shifting to lower wavenumbers in the solid state relative to those in the gas phase. The supramolecular studies confirmed the formation of centrosymmetric R22(8) rings, which correspond to the formation of dimers that stack parallel to the b direction. Other weak C-H...π interactions, essential for crystal growth, were found. The UV-Vis spectroscopic analysis showed a donor-acceptor process, where the amino group acts as a donor and the pyridine and pyrimidine rings act as acceptors. The reactive sites of the molecule were identified and their quantitative values were defined using the electrostatic potential model proposed in the multifunctional wave function analyzer multiwfn. The calculated interaction energies between pairs of molecules were used to visualize the electrostatic terms as the leading factors against the dispersion factors in the crystal-growth process. The docking results showed that the amino group of the pyrimidine moiety was simultaneously anchored by hydrogen-bonding interactions with the Asp427 and His407 protein residues. This compound could be key for the realization of a series of syntheses of molecules that could be used as possible inhibitors of chronic myelogenous leukemia.

Crystal structure of 2-fluoro-N-(1,3-thia-zol-2-yl)benzamide.

In the title compound, C10H7FN2OS, the mean plane of the central amide fragment (r.m.s. deviation = 0.048 Å) makes dihedral angles of 35.28 (8) and 10.14 (12)° with those of the fluoro-benzene and thia-zole rings, respectively. The thia-zole S and amide O atoms lie to the same side of the mol-ecule. In the crystal, pairs of N-H⋯N hydrogen bonds connect the mol-ecules into inversion dimers with R 2 (2)(8) motifs, and weak C-H⋯O inter-actions connect the mol-ecules into C(6) [001] chains. Together, the N-H⋯N and C-H⋯O hydrogen bonds generate (100) sheets.