《Discovery of novel VX-809 hybrid derivatives as F508del-CFTR correctors by molecular modeling, chemical synthesis and biological assays》 was written by Parodi, Alice; Righetti, Giada; Pesce, Emanuela; Salis, Annalisa; Tasso, Bruno; Urbinati, Chiara; Tomati, Valeria; Damonte, Gianluca; Rusnati, Marco; Pedemonte, Nicoletta; Cichero, Elena; Millo, Enrico. Quality Control of N,N-Dimethylformamide Dimethyl AcetalThis research focused onVX809 hybrid derivative preparation cystic fibrosis CFTR F508del; Aminoarylthiazole; CFTR Corrector; Cystic fibrosis; Docking; F508del-CFTR; Surface plasmon resonance. The article conveys some information:
Cystic fibrosis (CF) is the autosomal recessive disorder most recurrent in Caucasian populations. It is caused by different mutations in the cystic fibrosis transmembrane regulator protein (CFTR) gene, with F508del being the most common. During the last years, small-mol. therapy chosen to contrast CF relied on compounds that correct CFTR misfolding and ER retention (correctors such as VX-809), or defective channel gating (potentiators such as VX-770). Combination therapy with the two series of drugs has been applied, leading to the approval of several multi-drugs such as Orkambi. Despite this, this treatment proved to be only partially effective making the search for novel modulators an urgent need to contrast CF. Recently, we reported compound 2a as reference compound of a series of aminoarylthiazole-VX-809 hybrid derivatives exhibiting promising F508del-CFTR corrector ability. Herein, we report exploring the docking mode of the prototype VX-809 and of 2a in order to derive useful guidelines for the rational design of novel optimized analogs. To demonstrate exptl. their effective F508del-CFTR-binding and rescuing potential, the most promising derivatives had been synthesized and evaluated in biol. assays including YFP functional assay on F508del-CFTR CFBE41o-cells, trans epithelial elec. resistance (TEER) and surface plasmon resonance (SPR). This multidisciplinary strategy led to the discovery of a second series of hybrids including 7j and 7m endowed with higher potency than the prototype. In addition to this study using N,N-Dimethylformamide Dimethyl Acetal, there are many other studies that have used N,N-Dimethylformamide Dimethyl Acetal(cas: 4637-24-5Quality Control of N,N-Dimethylformamide Dimethyl Acetal) was used in this study.
N,N-Dimethylformamide Dimethyl Acetal(cas: 4637-24-5) belongs to anime. Primary amines having a tertiary alkyl group (R3CNH2) are difficult to prepare with most methods but are made industrially by the Ritter reaction. In this method a tertiary alcohol reacts with hydrogen cyanide (HCN) in the presence of a concentrated strong acid; a formamide, RNH―CHO, is formed first, which then undergoes hydrolysis.Quality Control of N,N-Dimethylformamide Dimethyl Acetal
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