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    • 3. 发明授权
    • Template-fixed peptidomimetics
    • 模板固定肽模拟物
    • US08921325B2
    • 2014-12-30
    • US13764099
    • 2013-02-11
    • Universitaet ZuerichPolyphor Ltd.
    • Daniel ObrechtFrank GombertSteven J. DemarcoChristian LudinJan Wim VrijbloedKerstin MoehleJohn-Anthony RobinsonReshmi MukherjeeHeiko HenzeBarbara Romagnoli
    • A61K38/12C07K7/56
    • C07K7/56A61K38/00A61K38/12C07K7/64
    • The template-fixed β-hairpin peptidomimetics Cyclo(-Tyr-His-X-Cys-Ser-Ala-DPro-Dab-Arg-Tyr-Cys-Tyr-Gln-Lys-DPro-Pro), disulfide bond between Cys4 and Gys11, and pharmaceutically acceptable salts thereof, with X being Ala or Tyr, have CXCR4 antagonizing properties and can be used for preventing HIV infections in healthy individuals or for slowing and halting viral progression in infected patients; or where Cancer is mediated or resulting from CXCR4 receptor activity; or where immunological diseases are mediated or resulting from CXCR4 receptor activity; or for treating immuno suppression; or, in particular, for stem cell mobilization of peripheral blood stem cells and/or mesenchymal stem cell (MSC) and/or other stem cells which retention depend on the CXCR4-receptor. These β-hairpin peptidomimetics can be manufactured by a process which is based on a mixed solid- and Solution phase synthetic strategy, using methods which are well known to those adequately skilled in peptide chemistry.
    • 模板固定和固定肽模拟物Cyclo(-Tyr-His-X-Cys-Ser-Ala-DPro-Dab-Arg-Tyr-Cys-Tyr-Gln-Lys-DPro-Pro),Cys4和 Gys11及其药学上可接受的盐,X为Ala或Tyr,具有CXCR4拮抗性质,可用于预防健康个体的HIV感染或减缓和阻止感染患者的病毒进展; 或其中癌症介导或由CXCR4受体活性产生; 或其中免疫性疾病介导或由CXCR4受体活性产生; 或用于治疗免疫抑制; 或特别是用于干细胞移动外周血干细胞和/或间充质干细胞(MSC)和/或其它干细胞,其保留取决于CXCR4-受体。 这些和包装肽模拟物可以通过使用基于混合固相和溶液相合成策略的方法,使用肽化学方面熟练的技术熟知的方法来制造。