16192-21-5Relevant academic research and scientific papers
Design, Synthesis, and Evaluation of Novel Enterovirus 71 Inhibitors as Therapeutic Drug Leads for the Treatment of Human Hand, Foot, and Mouth Disease
Zhang, Min,Wang, Ying,He, Wanli,Sun, Yao,Guo, Yan,Zhong, Weilong,Gao, Qiang,Liao, Mingyang,Wang, Xiangxi,Cai, Yan,Guo, Yu,Rao, Zihe
, p. 1233 - 1244 (2020/03/10)
Human hand, foot, and mouth disease (HFMD) is a serious public health threat with high infection rates in children and infants who reside in Asia and the Pacific regions, and no effective drugs are currently available. Enterovirus 71 (EV71) and coxsackievirus A16 are the major etiological pathogens. Based on an essential hydrophobic pocket on the viral capsid protein VP1, we designed and synthesized a series of small molecular weight compounds as inhibitors of EV71. A potential drug candidate named NLD-22 exhibited excellent antiviral activity (with an EC50 of 5.056 nM and a 100% protection rate for mice at a dose of 20 mg/kg) and low toxicity. NLD-22 had a favorable pharmacokinetic profile. High-resolution cryo-electron microscopy structural analysis confirmed NLD-22 bound to the hydrophobic pocket in VP1 to block viral infection. In general, NLD-22 was indicated to be a promising potential drug candidate for the treatment of HFMD.
HYDROLYSE BASIQUE ET DECARBOXYLATION D'ESTERS ALLOPHANIQUES EN MILIEU MIXTE ACETONITRILE-EAU: CATALYSE BIFONCTIONNELLE PAR UNE ENTITE FORMEE ENTRE BASE ET SOLVANT
Monnier, E.,Klaebe, A,Perie, J. J.
, p. 3067 - 3070 (2007/10/02)
Base catalysed hydrolysis of allophanic esters-models of carboxybiotine- in acetonitrile/water mixture, shows a sharp increase in rate constant in the range of 0.1-0.3 M in water, with a maximum which is interpreted as a balance between two desolvation terms, one concerning the nucleophile, the other the anionic transition state.Moreover, in acetonitrile/water mixtures at low water content (2.10-2 M), a fast hydrolysis (kexpca.0.5 s-1 at 20 deg C) of allophanic esters (carboxy-biotin models) is observed due to catalysis by the enolate of acetamide.This speciesalso catalyses the decarboxylation step, likely behaving as a bifunctional catalyst.
