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Synthesis of 4-oxotetrahydropyrimidine-1(2H)-carboxamides derivatives as capsid assembly modulators of hepatitis B virus

Med Chem Res. 2021-01;

Nicky Hwang, Haiqun Ban, Junjun Chen, Julia Ma, Hui Liu, Patrick Lam, John Kulp, Stephan Menne, Jinhong Chang, Ju-Tao Guo, Yanming Du

Products/Services Used	Details	Operation
Proteins, Expression, Isolation and Analysis	using MOPs running buffer (Genscript, catalog No. M00138)	Get A Quote

摘要

We report herein the synthesis and evaluation of phenyl ureas derived from 4-oxotetrahydropyrimidine as novel capsid assembly modulators of hepatitis B virus (HBV). Among the derivatives, compound () and several analogs showed an activity of submicromolar EC against HBV and low cytotoxicities (>50?μM). Structure-activity relationship studies revealed a tolerance for an additional group at position 5 of 4-oxotetrahydropyrimidine. The mechanism study indicates that compound () is a type II core protein allosteric modulator (CpAMs), which induces core protein dimers to assemble empty capsids with fast electrophoresis mobility in native agarose gel. These compounds may thus serve as leads for future developmen... More