European Journal of Medicinal Chemistry p. 480 - 501 (2019)
Update date:2022-08-15
Topics:
Pan, Ting
Ding, Yanchao
Wu, Liyang
Liang, Liting
He, Xin
Li, Qianwen
Bai, Chuan
Zhang, Hui
The capsid assembly is an essential step for Hepatitis B Virus (HBV) life cycle and is an important target for anti-HBV drug development. In this report, we identified a hit compound with aminothiazole structure by the high throughput screening (HTS) which inhibited the interaction of HBV capsid protein within the cells. The structure hopping and SAR studies of the hit compound afforded compound 79 with potent anti-HBV replication activity and good basic drug-like properties. The working mechanism studies showed that compound 79 could bind to the similar binding site of known HBV capsid inhibitor with heteroaryldihydropyrimidine (HAP) scaffold, through similar hydrophobic interactions but with a different hydrogen bond. This compound exerted potent inhibitory effect upon HBV production, either in cell culture or in mice with no obvious acute toxicity. We propose that further development of this compound could lead to novel potent anti-HBV inhibitors that target HBV capsid assembly.
View MoreContact:+86-913-2223392
Address:No. 32, Xinanjing Road, Weinan City, Shaanxi Province, 714000, China
Hubei Lingsheng Pharmaceuticals Co., Ltd.
Contact:+86-0710-3538058
Address:Xiangyang City Xiangcheng Economic Development Zone, Hubei Province
Lyrin Industrial Corporation Limited
Contact:86-731-82571800
Address:Rm 2408,Asia Economy International Building,Shaoshan Road South,Yuhua District,Changsha,Hunan,China
ShangHai BMG Chemical Co., Ltd
Contact:+86-13524845543
Address:Room 602, no 291 sikai road shanghai
Zhejiang kehong chemical co., ltd
Contact:0086-575-85522000
Address:xiner center RD binhai industrial zone shaoxing zhejiang province P.R.China,312073
Doi:10.1002/hlca.19640470809
(1964)Doi:10.1039/C6CE02292H
(2017)Doi:10.1021/jo00816a011
(1971)Doi:10.1021/ol7030153
(2008)Doi:10.1039/j39710000343
(1971)Doi:10.1016/0022-328X(85)87383-6
(1985)