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Design, Synthesis, and Evaluation of Tetrahydropyrrolo[1,2-c]pyrimidines as Capsid Assembly Inhibitors for HBV Treatment.

ABSTRACT: The discovery of novel tetrahydropyrrolo[1,2-c]pyrimidines derivatives from Bay41_4109 as hepatitis B virus (HBV) inhibitors is herein reported. The structure-activity relationship optimization led to one highly efficacious compound 28a (IC50 = 10 nM) with good PK profiles and the favorite L/P ratio. The hydrodynamic injection model in mice clearly demonstrated the efficacy of 28a against HBV replication.

SUBMITTER: Li X

PROVIDER: S-EPMC5601373 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature

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Design, Synthesis, and Evaluation of Tetrahydropyrrolo[1,2-c]pyrimidines as Capsid Assembly Inhibitors for HBV Treatment.

Li Xiaolin X Zhou Kai K He Haiying H Zhou Qiong Q Sun Ya Y Hou Lijuan L Shen Liang L Wang Xiaofei X Zhou Yuedong Y Gong Zhen Z He Shibo S Jin Huangtao H Gu Zhengxian Z Zhao Shuyong S Zhang Long L Sun Chunyan C Zheng Shansong S Cheng Zhe Z Zhu Yidong Y Zhang Minghui M Li Jian J Chen Shuhui S

ACS medicinal chemistry letters 20170824 9

The discovery of novel tetrahydropyrrolo[1,2-c]pyrimidines derivatives from Bay41_4109 as hepatitis B virus (HBV) inhibitors is herein reported. The structure-activity relationship optimization led to one highly efficacious compound 28a (IC50 = 10 nM) with good PK profiles and the favorite L/P ratio. The hydrodynamic injection model in mice clearly demonstrated the efficacy of 28a against HBV replication. ...[more]

PMID: 28947946

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