New Amidated 3,6-Diphenylated Imidazopyridazines with Potent Antiplasmodium Activity Are Dual Inhibitors of Plasmodium Phosphatidylinositol-4-kinase and cGMP-Dependent Protein Kinase was written by Cheuka, Peter Mubanga;Centani, Luyanda;Arendse, Lauren B.;Fienberg, Stephen;Wambua, Lynn;Renga, Shoneeze S.;Dziwornu, Godwin Akpeko;Kumar, Malkeet;Lawrence, Nina;Taylor, Dale;Wittlin, Sergio;Coertzen, Dina;Reader, Janette;van der Watt, Mariette;Birkholtz, Lyn-Marie;Chibale, Kelly. And the article was included in ACS Infectious Diseases in 2021.Recommanded Product: 109-85-3 The following contents are mentioned in the article:
Recent studies on 3,6-diphenylated imidazopyridazines have demonstrated impressive in vitro activity and in vivo efficacy in mouse models of malaria infection. Herein, we report the synthesis and antiplasmodium evaluation of a new series of amidated analogs and demonstrate that these compounds potently inhibit Plasmodium phosphatidylinositol-4-kinase (PI4K) type IIIβ while moderately inhibiting cyclic guanidine monophosphate (cGMP)-dependent protein kinase (PKG) activity in vitro. Using in silico docking, we predict key binding interactions for these analogs within the ATP (ATP)-binding site of PI4K and PKG, paving the way for structure-based optimization of imidazopyridazines targeting both Plasmodium PI4K and PKG. While several derivatives showed low nanomolar antiplasmodium activity (IC50 < 100 nM), some compounds, including piperazine analog I, resulted in strong dual PI4K and PKG inhibition. The compounds also demonstrated transmission-blocking potential, evident from their potent inhibition of early- and late-stage gametocytes. Finally, the current compounds generally showed improved aqueous solubility and reduced hERG (human ether-a-go-go-related gene) channel inhibition. This study involved multiple reactions and reactants, such as 2-Methoxyethylamine (cas: 109-85-3Recommanded Product: 109-85-3).
2-Methoxyethylamine (cas: 109-85-3) belongs to ethers. Volatile esters with characteristic odours are used in synthetic flavours, perfumes, and cosmetics. Certain volatile esters are used as solvents for lacquers, paints, and varnishes. Many esters have the potential for conformational isomerism, but they tend to adopt an s-cis (or Z) conformation rather than the s-trans (or E) alternative, due to a combination of hyperconjugation and dipole minimization effects. The preference for the Z conformation is influenced by the nature of the substituents and solvent, if present. Lactones with small rings are restricted to the s-trans (i.e. E) conformation due to their cyclic structure.Recommanded Product: 109-85-3
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