Arylglyoxals which are new compounds and which are active as hypoglycemic agents.
芳基乙二醛是一种新化合物,具有降血糖剂的活性。
SAR-Based Optimization of a 4-Quinoline Carboxylic Acid Analogue with Potent Antiviral Activity
作者:Priyabrata Das、Xiaoyi Deng、Liang Zhang、Michael G. Roth、Beatriz M. A. Fontoura、Margaret A. Phillips、Jef K. De Brabander
DOI:10.1021/ml300464h
日期:2013.6.13
It is established that drugs targeting viral proteins are at risk of generating resistant strains. However, drugs targeting host factors can potentially avoid this problem. Herein, we report structure-ctivity relationship studies leading to the discovery of a very potent lead compound 6-fluoro-2-(5-isopropyl-2-methyl-4-phenoxyphenyl) quinoline -4-carboxylic acid (C44) that inhibits human dihydroorotate dehydrogenase (DHODH) with an IC50 of 1 nM and viral replication of VSV and WSN-Influenza with an EC50 of 2 nM and 41 nM. We also solved the X-ray structure of human DHODH bound to C44, providing structural insight into the potent inhibition of biaryl ether analogues of brequinar.
6-(4′-Aryloxy-phenyl)vinyl-1,2,4-trioxanes: A new series of orally active peroxides effective against multidrug-resistant Plasmodium yoelii in Swiss mice
A new series of 6-(4'-aryloxy-phenyl)vinyl-1,2,4-trioxanes 10a-d, 11a-d, and 12a-d have been synthesized and evaluated for their antimalarial activity against multidrug-resistant Plasmodium yoelii in Swiss mice by oral route. Trioxanes 10b and 10c, the two most active compounds of the series, provided 100% protection to the infected mice at 48 mg/kg x 4 days. Clinically useful drug beta-arteether provided 100% and 20% protection at 48 mg/kg x 4 days and 24 mg/kg x 4 days, respectively, in this model. (C) 2010 Elsevier Ltd. All rights reserved.