原创力文档discovery of hepatitis b virus capsid assembly inhibitors leading to a heteroaryldihydropyrimidine based clinical candidate (gls4)：（发现乙肝病毒衣壳组装抑制剂导致heteroaryldihydropyrimidine基础临床候选人(gls4)）.pdfVIP
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discovery of hepatitis b virus capsid assembly inhibitors leading to a heteroaryldihydropyrimidine based clinical candidate (gls4)：（发现乙肝病毒衣壳组装抑制剂导致heteroaryldihydropyrimidine基础临床候选人(gls4)）
Bioorganic Medicinal Chemistry 25 (2017) 1042–1056
Contents lists available at ScienceDirect
Bioorganic Medicinal Chemistry
journal homepage: www.else /locate/bmc
Discovery of hepatitis B virus capsid assembly inhibitors leading to a
heteroaryldihydropyrimidine based clinical candidate (GLS4)
Qingyun Ren a,b, Xinchang Liu a,b, Zhonghua Luo a, Jing Li a, Chaolei Wang a,b, Siegfried Goldmann a,⇑,
Jiancun Zhang c, Yingjun Zhang a,⇑
a Sunshine Lake Pharma Co., Ltd, Dong Guan 523808, China
b Anti-infection Innovation Department, New Drug Research Institute, HEC Pharma Group, Dong Guan 523871, China
c Guangzhou Institute of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China
a r t i c l e i n f o a b s t r a c t
Article history: Inhibition of hepatitis B virus (HBV) capsid assembly is a novel strategy for the development of chronic
Received 16 November 2016 hepatitis B (CHB) therapeutics. Herein we described our lead optimization studies including the synthe-
Accepted 10 December 2016 sis, molecular docking studies and structure-activity relationship (SAR) studies of a series of novel
Available online 19 December 2016
heteroaryldihydropyrimidine (HAP) inhibitors of HBV capsid assembly inhibitors, and the discovery of
a potent inhibitor of HBV capsid assembly of GLS4 (ethyl 4-[2-bromo-4-fluorophenyl]-6-[morpholino-
Keywords: methyl]-2-[2-thiazolyl]-1,4-dihydro-pyrimidine-5-carboxylate) which is now in
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