发明申请
US20110189771A1 Novel Imino Sugar Derivatives Demonstrate Potent Antiviral Activity and Reducted Toxicity
有权
新型伊米诺糖衍生物证明有效的抗病毒活性和减少的毒性
- 专利标题: Novel Imino Sugar Derivatives Demonstrate Potent Antiviral Activity and Reducted Toxicity
- 专利标题(中): 新型伊米诺糖衍生物证明有效的抗病毒活性和减少的毒性
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申请号: US13061734申请日: 2009-09-02
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公开(公告)号: US20110189771A1公开(公告)日: 2011-08-04
- 发明人: Timothy M. Block , Jinhong Chang , Xiaodong Xu
- 申请人: Timothy M. Block , Jinhong Chang , Xiaodong Xu
- 申请人地址: US PA Doylestown
- 专利权人: INSTITUTE FOR HEPATITIS AND VIRUS RESEARCH
- 当前专利权人: INSTITUTE FOR HEPATITIS AND VIRUS RESEARCH
- 当前专利权人地址: US PA Doylestown
- 国际申请: PCT/US09/55658 WO 20090902
- 主分类号: C12N5/02
- IPC分类号: C12N5/02 ; C07D211/40
摘要:
Imino sugars, such as deoxynojirimycin (DNJ), are glucose analogues that selectively inhibit cellular α-glucosidase I and II (enzymes that process N-linked glycans in glycoprotein) and exhibit broad spectrum antiviral activities against many enveloped viruses. Previously we have reported a novel DNJ derivative, OSL-95II, with antiviral activity and reduced cytotoxicity. In order to develop imino sugars with more potent antiviral activity as well as improved toxicity profile, OSL-95II was modified by diversifying the nitrogen linked alkylated side chain. The antiviral activities were initially tested in bovine viral diarrhea virus (BVDV) infected MDBK cells, yielding several imino sugar derivatives with novel structure and superior antiviral activity and toxicity profile. Furthermore, these new compounds were shown to be active against Dengue virus (DV) and West Nile virus (WNV) infection in BHK cells where potent anti-DV activity having submicromolar EC50 values and SI of greater than 900. These compounds represent a new generation of iminio sugars and their analogues, having application in the clinical treatment of infection of DV and other members of flaviviridae.