Bioorganic and Medicinal Chemistry (2021)
Update date:2022-09-26
Topics:
Gu, Xiaoke
Zhang, Yinpeng
Zou, Yueting
Li, Xin
Guan, Mingyu
Zhou, Qingqing
Qiu, Jingying
As a continuation of our previous work, a series of new phenyl acrylamide derivatives (4Aa-g, 4Ba-t, 5 and 6a-c) were designed and synthesized as non-nucleoside anti-HBV agents. Among them, compound 4Bs could potently inhibit HBV DNA replication in wild-type and lamivudine (3TC)/entecavir resistant HBV mutant strains with IC50 values of 0.19 and 0.18 μM, respectively. Notably, the selective index value of 4Bs was above 526, indicating the favorable safety profile. Interestingly, unlike nucleoside analogue 3TC, 4Bs could significantly inhibit 3.5 kb pgRNA expression. Molecular docking study revealed that 4Bs could fit well into the dimer-dimer interface of HBV core protein by hydrophobic, π–π and H-bond interactions. Considering the potent anti-HBV activity, low toxicity and diverse anti-HBV mechanism from that of nucleoside anti-HBV agent 3TC, compound 4Bs might be a promising lead to develop novel non-nucleoside anti-HBV therapeutic agents, and warranted further investigation.
View MoreSHENYANG COMEBOARD TECHNOLOGY CO., LTD
Contact:+86-24-25724626
Address:Room2210,Tianbao International Building,No.8-1 Weigong South Street,Tiexi District,Shenyang,China
Hefei Highzone Fine Chemical S&T CO.,LTD
Contact:86-0551-63663560
Address:room 1801 NO. 24 Shuguang RD.
Nanjing Chemzam Pharmtech Co., Ltd.
Contact:+86-25-86462165,+86-13915979898
Address:C5-1,6 Maiyue Road,Maigaoqiao,Nanjing,Jiangsu,China
Contact:0550-7041128 0550-7090578
Address:Wangdian Street,Xinjie Town
Contact:86-571-61063068
Address:LINAN
Doi:10.1002/hlca.19740570815
(1974)Doi:10.1016/S0960-894X(00)00348-6
(2000)Doi:10.1016/S0040-4020(01)01063-8
(2001)Doi:10.1080/104265090921083
(2005)Doi:10.1016/S0040-4020(01)00049-7
(2001)Doi:10.1016/j.apcata.2012.12.021
(2013)