Schwertz, Geoffrey published the artcileAntimalarial Inhibitors Targeting Serine Hydroxymethyltransferase (SHMT) with in Vivo Efficacy and Analysis of their Binding Mode Based on X-ray Cocrystal Structures, Quality Control of 596819-12-4, the publication is Journal of Medicinal Chemistry (2017), 60(12), 4840-4860, database is CAplus and MEDLINE.
Target-based approaches towards new antimalarial treatments are highly valuable to prevent resistance development. The authors report several series of pyrazolopyran-based inhibitors targeting the enzyme serine hydroxymethyltransferase (SHMT), designed to improve microsomal metabolic stability and to identify suitable candidates for in vivo efficacy evaluation. The best ligands inhibited Plasmodium falciparum (Pf) and Arabidopsis thaliana (At) SHMT in target assays and PfNF54 strains in cell-based assays with values in the low nanomolar range (3.2-55 nM). A set of carboxylate derivatives demonstrated markedly improved in vitro metabolic stability (t1/2 > 2 h). A selected ligand showed significant in vivo efficacy with 73% of parasitemia reduction in a mouse model. Five new cocrystal structures with PvSHMT were solved at 2.3-2.6 Å resolution, revealing a unique water-mediated interaction with Tyr63 at the end of the para-aminobenzoate channel. They also displayed the high degree of conformational flexibility of the Cys364-loop lining this channel.
Journal of Medicinal Chemistry published new progress about 596819-12-4. 596819-12-4 belongs to ethers-buliding-blocks, auxiliary class Thiophene,Boronic acid and ester,Ether,Boronate Esters,Boronic acid and ester, name is 2-(5-Methoxythiophen-2-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane, and the molecular formula is C12H10F2Si, Quality Control of 596819-12-4.
Referemce:
https://en.wikipedia.org/wiki/Ether,
Ether | (C2H5)2O – PubChem