Synthesis and Evaluation of N-Phenyl-3-sulfamoyl-benzamide Derivatives as Capsid Assembly Modulators Inhibiting Hepatitis B Virus (HBV)

  • J Med Chem. 2018 Jul 26;61(14):6247-6260. 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
Affiliations
  • 1. Janssen Pharmaceutica NV , Janssen Pharmaceutical Companies of Johnson & Johnson , Turnhoutseweg 30 , 2340 Beerse , Belgium.
  • 2. WuXi AppTec , 288 Fute Zhong Road , China (Shanghai) Pilot Free Trade Zone; Shanghai 200131 , PR China.
PMID: 29906396 DOI: 10.1021/acs.jmedchem.8b00654
Abstract

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.

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