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

Autor: Vandyck K; Janssen Pharmaceutica NV , Janssen Pharmaceutical Companies of Johnson & Johnson , Turnhoutseweg 30 , 2340 Beerse , Belgium., Rombouts G; Janssen Pharmaceutica NV , Janssen Pharmaceutical Companies of Johnson & Johnson , Turnhoutseweg 30 , 2340 Beerse , Belgium., Stoops B; Janssen Pharmaceutica NV , Janssen Pharmaceutical Companies of Johnson & Johnson , Turnhoutseweg 30 , 2340 Beerse , Belgium., Tahri A; Janssen Pharmaceutica NV , Janssen Pharmaceutical Companies of Johnson & Johnson , Turnhoutseweg 30 , 2340 Beerse , Belgium., Vos A; Janssen Pharmaceutica NV , Janssen Pharmaceutical Companies of Johnson & Johnson , Turnhoutseweg 30 , 2340 Beerse , Belgium., Verschueren W; Janssen Pharmaceutica NV , Janssen Pharmaceutical Companies of Johnson & Johnson , Turnhoutseweg 30 , 2340 Beerse , Belgium., Wu Y; WuXi AppTec , 288 Fute Zhong Road , China (Shanghai) Pilot Free Trade Zone; Shanghai 200131 , PR China., Yang J; WuXi AppTec , 288 Fute Zhong Road , China (Shanghai) Pilot Free Trade Zone; Shanghai 200131 , PR China., Hou F; WuXi AppTec , 288 Fute Zhong Road , China (Shanghai) Pilot Free Trade Zone; Shanghai 200131 , PR China., Huang B; WuXi AppTec , 288 Fute Zhong Road , China (Shanghai) Pilot Free Trade Zone; Shanghai 200131 , PR China., Vergauwen K; Janssen Pharmaceutica NV , Janssen Pharmaceutical Companies of Johnson & Johnson , Turnhoutseweg 30 , 2340 Beerse , Belgium., Dehertogh P; Janssen Pharmaceutica NV , Janssen Pharmaceutical Companies of Johnson & Johnson , Turnhoutseweg 30 , 2340 Beerse , Belgium., Berke JM; Janssen Pharmaceutica NV , Janssen Pharmaceutical Companies of Johnson & Johnson , Turnhoutseweg 30 , 2340 Beerse , Belgium., Raboisson P; Janssen Pharmaceutica NV , Janssen Pharmaceutical Companies of Johnson & Johnson , Turnhoutseweg 30 , 2340 Beerse , Belgium.
Jazyk: angličtina
Zdroj: Journal of medicinal chemistry [J Med Chem] 2018 Jul 26; Vol. 61 (14), pp. 6247-6260. Date of Electronic Publication: 2018 Jul 03.
DOI: 10.1021/acs.jmedchem.8b00654
Abstrakt: 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.
Databáze: MEDLINE
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