Synthesis and antiviral activity of 2′‐deoxy‐6′‐substituted carbocyclic nucleosides. (18th December 2021)

• Record Type: Journal Article
• Authors: Xue, Haitao; Guo, Shuang; Hu, Tianwen; Wei, Daibao; Xie, Yuanchao; Shen, Jingshan
• Is Part Of: Chemical biology & drug design. Volume 99:Number 4(2022)
• Page Start: 561
• Page End: 572
• Publication Date: 2021-12-18
• Subjects: 2′‐deoxy carbocyclic nucleoside -- antiviral activity -- hepatitis B virus -- Mitsunobu reaction; Drugs -- Design -- Periodicals; Pharmaceutical chemistry -- Periodicals; Biochemistry -- Periodicals; 615.19005
• DOI: 10.1111/cbdd.13998
• Languages: English
• ISSNs: 1747-0277

Abstract

Abstract: A series of 2′‐deoxy carbocyclic nucleosides characterized by various 6′‐substitutions were synthesized and evaluated for their antiviral activities against three viruses, including hepatitis B virus (HBV), hepatitis C virus, and influenza virus. The in vitro antiviral assays indicated that these nucleosides only showed inhibitory activities against HBV, and the substituted groups at the 6′ position significantly affected the activity. Among them, the guanosine analog 2b bearing a 6′‐α‐hydroxyl methyl group was the most potent compound with an EC50 value of 80 nM. The present study provided useful information for the discovery of antiviral carbocyclic nucleosides. Abstract : A series of 6′‐substituted carbocyclic nucleosides were synthesized and exhibited promising anti‐HBV activity, of which 6′‐α‐substituted carbocyclic nucleosides are more effective than those with 6′‐β‐substitution. The guanosine analog 2b bearing a 6′‐α‐hydroxyl methyl group was the most potent compound with EC50 value of 80 nM.