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    • 32. 发明申请
    • Semi-Synthetic Desmethyl-Vancomycin-Based Glycopeptides With Antibiotic Activity
    • 具有抗生素活性的半合成去甲基 - 万古霉素基糖肽
    • US20090131304A1
    • 2009-05-21
    • US12268364
    • 2008-11-10
    • Daniel ChuYaohui LeiYu BaiZhi-Jie NiJohn Jian-Xin Wang
    • Daniel ChuYaohui LeiYu BaiZhi-Jie NiJohn Jian-Xin Wang
    • A61K38/12C07K9/00
    • C07K9/008A61K38/00
    • Semi-synthetic glycopeptides that have antibacterial activity are based on modifications of the desmethyl-vancomycin scaffold, in particular, acylation of the amino substituent on the amino-substituted sugar moiety on this scaffold with certain acyl groups; and/or conversion of the acid moiety on the macrocyclic ring of this scaffolds to certain substituted amides. In addition, compounds of the invention include desmethyl-vancomycin scaffolds on which the acid moiety on the macrocyclic ring is converted to certain substituted amides and the amino substituent on the amino-substituted sugar moiety is alkylated with certain alkyl groups. Also provided are methods for synthesis of the compounds, pharmaceutical compositions containing the compounds, and methods of use of the compounds for the treatment and/or prophylaxis of diseases, especially bacterial infections.
    • 具有抗菌活性的半合成糖肽基于脱甲基万古霉素支架的修饰,特别是在该支架上具有某些酰基的氨基取代的糖部分上的氨基取代基的酰化; 和/或将该支架的大环上的酸部分转化为某些取代的酰胺。 此外,本发明的化合物包括去甲基 - 万古霉素支架,大环上的酸部分转化为某些取代的酰胺,氨基取代的糖部分上的氨基取代基被某些烷基烷基化。 还提供了合成化合物的方法,含有化合物的药物组合物,以及用于治疗和/或预防疾病,特别是细菌感染的化合物的使用方法。
    • 40. 发明申请
    • NOVEL SEMI-SYNTHETIC GLYCOPEPTIDES AS ANTIBACTERIAL AGENTS
    • 新型半合成糖苷作为抗菌剂
    • US20120129763A1
    • 2012-05-24
    • US13358374
    • 2012-01-25
    • Daniel ChuTao Ye
    • Daniel ChuTao Ye
    • A61K38/14A61P31/04C07K9/00
    • C07K9/008
    • Semi-synthetic glycopeptides having antibacterial activity are described, in particular, the semi-synthetic glycopeptides described herein are made by chemical modification of a glycopeptide (Compound A, Compound B, Compound H or Compound C) or monosaccharide made by hydrolyzing the disaccharide moiety of the amino acid-4 of the parent glycopeptide in acidic medium to give the amino acid-4 monosaccharide; conversion of the monosaccharide to the amino-sugar derivative; acylation of the amino substituent on the amino acid-4 amino-substituted sugar moiety on these scaffolds with certain acyl groups; and conversion of the acid moiety on the macrocyclic ring of these scaffolds to certain substituted amides. Key reaction is the treatment of properly protected intermediate compound with isocyanate or carrying a Hofmann degradation of the primary amide of the 3rd amino acid asparagines with phenyl-bis-trifluoroacetate to give the primary amine. Also provided are methods for the synthesis of the compounds, pharmaceutical compositions containing the compounds, and methods of use of the compounds for the treatment and/or prophylaxis of diseases, especially bacterial infections.
    • 具体描述了具有抗菌活性的半合成糖肽,特别是本文所述的半合成糖肽通过化学修饰糖肽(化合物A,化合物B,化合物H或化合物C)或通过水解二糖部分 在酸性介质中母体糖肽的氨基酸-4得到氨基酸-4单糖; 单糖转化为氨基糖衍生物; 在这些支架上的氨基酸4氨基取代的糖部分上的氨基取代基被某些酰基酰化; 并将这些支架的大环上的酸部分转化为某些取代的酰胺。 关键反应是用异氰酸酯处理适当保护的中间体化合物或者用苯基二 - 三氟乙酸盐对第三氨基酸天门冬酰胺的伯酰胺进行霍夫曼降解,得到伯胺。 还提供了合成化合物的方法,含有该化合物的药物组合物,以及该化合物用于治疗和/或预防疾病,特别是细菌感染的方法。