475587-23-6Relevant academic research and scientific papers
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
Arango-Daravi?a, Kevin,Kennedy, Alan R.,Moreno-Fuquen, Rodolfo
, p. 621 - 632 (2021/10/12)
The synthesis, crystal structure and spectroscopic and electronic properties of N-(2-methyl-5-nitrophenyl)-4-(pyridin-2-yl)pyrimidin-2-amine (NPPA), C16H13-N5O2, 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-1for 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.
An optimized approach in the synthesis of imatinib intermediates and analogues
Kinigopoulou,Filippidou,Gogou,Giannousi,Fouka,Ntemou,Alivertis,Georgis,Brentas,Polychronidou,Voulgari,Theodorou,Skobridis
, p. 61458 - 61467 (2016/07/12)
We revisited the classical synthetic procedure for imatinib synthesis providing an improved and optimized approach in the preparation of a series of new imatinib analogues. The proposed methodology effectively overcomes certain problematic steps, saves time and labor, provides a very high yield and purity and has the potential to be used for the synthesis of many analogues. The formation of the desired guanidine salt 4, one of the key steps to the imatinib synthesis, was proceeded almost quantitatively by the reaction of the hydrochloride of the suitable aniline 3 with excess of molten cyanamide, without any solvent. Pure arylamine intermediates 6a-d were obtained quantitatively in a short reaction time after reduction of the nitro group of the intermediate pyrimidines 5a-d with hydrogen over the Adam's catalyst. In addition, the application of this optimized approach can be extended in the synthesis of nilotinib and its analogues intermediates.
A facile total synthesis of imatinib base and its analogues
Liu, Yi-Feng,Wang, Cui-Ling,Bai, Ya-Jun,Han, Ning,Jiao, Jun-Ping,Qi, Xiao-Li
, p. 490 - 495 (2013/01/03)
Imatinib and its analogues were successfully synthesized by an improved method in 19.5-46.2% total yield of six main steps. Pyrimidinyl amine was prepared by the reaction of enaminone and guanidine nitrate without the use of a toxic cyanamide. N-(2-Methyl-5-nitrophenyl)-4-(pyridin-3-yl) pyrimidin-2-amine as a key intermediate for the synthesis of imatinib was prepared by coppercatalyzed iV-arylation of heteroarylamme in 82% yield. The copper salts were used instead of the expensive palladium compounds in this C-N bond-forming reaction. The intermediate nitro compound was reduced by a N2H 4.H2O/FeCl3/C system using water as a solvent in good yield.
Pyridylpyrimidine derivatives as effective compounds against prion diseases
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, (2008/06/13)
The present invention relates to pyridylpyrimidine derivatives of the general formula (I): wherein R represents hydrogen or methyl and Z represents nitrogen containing functional groups, the use of the pyridylpyrimidine derivatives as pharmaceutically active agents, especially for the prophylaxis and/or treatment of prion infections and prion diseases, as well as compositions containing at least one pyridylpyrimidine derivative and/or pharmaceutically acceptable salt thereof. Furthermore, the present invention is directed to methods for preventing and/or treating prion infections and prion diseases using said pyridylpyrimidine derivatives. Human cellular protein kinases, phosphatases and cellular signal transduction molecules are disclosed as targets for detecting, preventing and/or treating prion infections and diseases, especially BSE, vCJD, or CJD which can be inhibited by the inventive pyridylpyrimidine derivatives.
