Toviwek, Borvornwat; Phuangsawai, Oraphan; Konsue, Adchatawut; Hannongbua, Supa; Riley, Jennifer; Mutter, Nicole; Anderson, Mark; Webster, Lauren; Hallyburton, Irene; Read, Kevin D.; Gleeson, M. Paul published their research in Bioorganic & Medicinal Chemistry in 2021. The article was titled 《Preparation, biological & cheminformatics-based assessment of N2,N4-diphenylpyrimidine-2,4-diamine as potential Kinase-targeted antimalarials》.Application In Synthesis of 2,4-Dichloropyrimidine The article contains the following contents:
Twenty eight new N2,N4-diphenylpyrimidine-2,4-diamines have been prepared in order to expand our understanding of the anti-malarial SAR of the scaffold. The aim of the study was to make structural modifications to improve the overall potency, selectivity and solubility of the series by varying the anilino groups attached to the 2- and 4-position. We evaluated the activity of the compounds against Plasmodium falciparum (Pf) 3D7, cytotoxicity against HepG2, % inhibition at a panel of 10 human kinases, solubility, permeability and lipophilicity, and human and rat in vitro clearance. 11 was identified as a potent anti-malarial with an IC50 of 0.66 μM at the 3D7 strain and a selectivity (SI) of ∼ 40 in terms of cytotoxicity against the HepG2 cell line. It also displayed low exptl. logD7.4 (2.27), reasonable solubility (124 μg/mL), good metabolic stability, but low permeability. A proteo-chemometric workflow was employed to identify putative Pf targets of the most promising compounds Ligand-based similarity searching of the ChEMBL database led to the identification of most probable human targets. These were then used as input for sequence-based searching of the Pf proteome. Homol. modeling and mol. docking were used to evaluate whether compounds could indeed bind to these targets with valid binding modes. In vitro biol. testing against close human analogs of these targets was subsequently undertaken. This allowed us to identify potential Pf targets and human anti-targets that could be exploited in future development. In the part of experimental materials, we found many familiar compounds, such as 2,4-Dichloropyrimidine(cas: 3934-20-1Application In Synthesis of 2,4-Dichloropyrimidine)
2,4-Dichloropyrimidine(cas: 3934-20-1) is a member of organic chlorides. Organic chloride content in crude oil can be detected through specialized laboratory analysis. Care and attention are essential while sampling and testing.Application In Synthesis of 2,4-Dichloropyrimidine
Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia