Prodrug Strategies for the Development of beta-L-5-((E)-2-Bromovinyl)-1-((2S,4S)-2-(hydroxymethyl)-1,3-(dioxolane-4-yl))uracil (L-BHDU) against Varicella Zoster Virus (VZV)

Singh Uma S.; Konreddy Ananda K.; Kothapalli YugandharLiu DongmeiLloyd Megan G.Annavarapu VidyaWhite Catherine A.Bartlett Michael. G.Moffat Jennifer F.Chu Chung K.

首页> 外文期刊>Journal of Medicinal Chemistry >Prodrug Strategies for the Development of beta-L-5-((E)-2-Bromovinyl)-1-((2S,4S)-2-(hydroxymethyl)-1,3-(dioxolane-4-yl))uracil (L-BHDU) against Varicella Zoster Virus (VZV)

【24h】

Prodrug Strategies for the Development of beta-L-5-((E)-2-Bromovinyl)-1-((2S,4S)-2-(hydroxymethyl)-1,3-(dioxolane-4-yl))uracil (L-BHDU) against Varicella Zoster Virus (VZV)

机译：Prodrug Strategies for the Development of beta-L-5-((E)-2-Bromovinyl)-1-((2S,4S)-2-(hydroxymethyl)-1,3-(dioxolane-4-yl))uracil (L-BHDU) against Varicella Zoster Virus (VZV)

获取原文

获取原文并翻译 | 示例

掌桥外文数据库（机构版） >>

开具论文收录证明 >>

文献代查 >>

页面导航

摘要
著录项
相关主题

摘要

Varicella zoster virus (VZV) establishes lifelong infection after primary disease and can reactivate. Several drugs are approved to treat VZV diseases, but new antivirals with greater potency are needed. Previously, we identified beta-L-5-((E)-2-bromovinyl)-1-((2S,4S)-2-(hydroxymethyl)-1,3-(dioxo-lane-4-yl))uracil (L-BHDU, 1), which had significant anti-VZV activity. In this communication, we report the synthesis and evaluation of numerous L-BHDU prodrugs: amino acid esters (14-26), phosphoramidates (33-34), long-chain lipids (ODE-L-BHDU-MP, 38, and HDP-L-BHDU-MP, 39), and phosphate ester prodrugs (POM-L-BHDU-MP, 41, and POC-L-BHDU-MP, 47). The amino acid ester L-BHDU prodrugs (L-phenylalanine, 16, and L-valine, 17) had a potent antiviral activity with EC50 values of 0.028 and 0.030 mu M, respectively. The phosphate ester prodrugs POM-L-BHDU-MP and POC-L-BHDU-MP had a significant anti-VZV activity with EC50 values of 0.035 and 0.034 mu M, respectively, and no cellular toxicity (CC50 > 100 mu M) was detected. Out of these prodrugs, ODE-L-BHDU-MP (38) and POM-L-BHDU-MP (41) were selected for further evaluation in future studies.

著录项

来源
《Journal of Medicinal Chemistry》 |2023年第10期|7038-7053|共16页
作者
Singh Uma S.; Konreddy Ananda K.; Kothapalli YugandharLiu DongmeiLloyd Megan G.Annavarapu VidyaWhite Catherine A.Bartlett Michael. G.Moffat Jennifer F.Chu Chung K.;
展开▼
作者单位

Univ Georgia;

SUNY Upstate;

展开▼
收录信息
原文格式 PDF
正文语种英语
中图分类药学;
关键词
ANTI-HIV ACTIVITY; HERPES-ZOSTER; ANTIVIRAL ACTIVITY; REPLICATION; NUCLEOSIDE; PHOSPHORAMIDATE; PHOSPHONATES; PHOSPHATE; PROTEINS; URACIL;

Prodrug Strategies for the Development of beta-L-5-((E)-2-Bromovinyl)-1-((2S,4S)-2-(hydroxymethyl)-1,3-(dioxolane-4-yl))uracil (L-BHDU) against Varicella Zoster Virus (VZV)

摘要

著录项

相关主题

期刊订阅