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Tetrazole and triazole as bioisosteres of carboxylic acid: discovery of diketo tetrazoles and diketo triazoles as anti-HCV agents
SONG Wuhui 1,LIU Mingming 1,ZHONG Dongwei 2,YE Deyong 2 #,ZHOU Lu 2,YUAN Zhenghong 1 *
1.Shanghai Medical College, Fudan University, Shanghai 200032
2.School of Pharmacy, Fudan University, Shanghai 201203
*Correspondence author
#Submitted by
Subject:
Funding: Shanghai Committee of Science and Technology of China (No.Grant No.13ZR1403900), National Natural Science Foundation of China (No.No.20902013 and No.30973641), China Postdoctoral Science Foundation (No.No.2013M531126), National Basic Research Program of China (No.No.2009CB522504)
Opened online: 5 May 2017
Accepted by: none
Citation: SONG Wuhui,LIU Mingming,ZHONG Dongwei.Tetrazole and triazole as bioisosteres of carboxylic acid: discovery of diketo tetrazoles and diketo triazoles as anti-HCV agents[OL]. [ 5 May 2017] http://en.paper.edu.cn/en_releasepaper/content/4730608
 
 
In this paper, a series of diketo tetrazoles and diketo triazoles were designed and synthesized as bioisosteres of α, γ-diketo acid, the active site inhibitor of HCV (Hepatitis C virus) polymerase NS5B. Among the synthesized compounds, 4-(4-fluorobenzyloxy)phenyl diketo triazole (30) exhibited anti-HCV activity with an EC50 value of 3.9 μM and an SI value more than 128. The reduction of viral protein and mRNA levels were also validated, supportingthe anti-HCV activity of compound 30. These results provide convincing evidence that the diketo tetrazoles and diketo triazoles can be developed as bioisosteres of α,γ-diketo acid to exhibit potent inhibitory activity against HCV.
Keywords:anti-HCV activity; diketo tetrazoles; diketo triazoles; bioisosteres
 
 
 

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