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Synthesis and Evaluation of N-Phenyl-3-sulfamoyl-benzamide Derivatives as Capsid Assembly Modulators Inhibiting Hepatitis B Virus (HBV)
Journal of Medicinal Chemistry ( IF 7.3 ) Pub Date : 2018-06-15 00:00:00 , DOI: 10.1021/acs.jmedchem.8b00654
Koen Vandyck 1 , Geert Rombouts 1 , Bart Stoops 1 , Abdellah Tahri 1 , Ann Vos 1 , Wim Verschueren 1 , Yiming Wu 2 , Jingmei Yang 2 , Fuliang Hou 2 , Bing Huang 2 , Karen Vergauwen 1 , Pascale Dehertogh 1 , Jan Martin Berke 1 , Pierre Raboisson 1
Affiliation  

Small molecule induced hepatitis B virus (HBV) capsid assembly modulation is considered an attractive approach for new antiviral therapies against HBV. Here we describe efforts toward the discovery of a HBV capsid assembly modulator in a hit-to-lead optimization, resulting in JNJ-632, a tool compound used to further profile the mode of action. Administration of JNJ-632 (54) in HBV genotype D infected chimeric mice resulted in a 2.77 log reduction of the HBV DNA viral load.

中文翻译:

N-苯基-3-氨磺酰基-苯甲酰胺衍生物作为抑制乙型肝炎病毒(HBV)的衣壳装配调节剂的合成与评价

小分子诱导的乙型肝炎病毒(HBV)衣壳装配调节被认为是针对HBV的新抗病毒治疗的一种有吸引力的方法。在这里,我们描述了在铅到铅的优化中发现HBV衣壳装配调节剂的努力,从而产生了JNJ-632,这是一种用于进一步描述作用方式的工具化合物。在感染了HBV基因型D的嵌合小鼠中施用JNJ-632(54)导致HBV DNA病毒载量减少了2.77 log。
更新日期:2018-06-15
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