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    • 3. 发明申请
    • DISALICYLATE ANALOG BASED SIALYL LEWIS<x> MIMETICS
    • 基于模板的SIALYL LEWIS MIMETICS
    • WO9929706A3
    • 1999-08-12
    • PCT/US9825788
    • 1998-12-04
    • GLYCOMED INCSANKYO COANDERSON MARK BLEVY DANIEL EHOLME KEVIN R
    • ANDERSON MARK BLEVY DANIEL EHOLME KEVIN R
    • C07C65/105C07C65/40C07C66/02C07C69/94C07H15/18C07D309/10A61K31/70
    • C07H15/18C07C65/105C07C65/40C07C66/02C07C69/94
    • The present invention discloses medicaments that are selectin-ligand structural mimetics that bind to certain selectins wherein the mimetics may lack the sialic acid and/or fucose of the natural selecting ligand, sialyl Lewis (sLe ), but have a structure capable of mimicking the structural features necessary for selectin recognition. In particular, the invention compounds mimic the key structural features of the oligosaccharides responsible for selectin-mediated cell adhesion. These features consist of the charge-distance-coordination relationship between the carboxylic acid functionality of sialic acid at a distance of 8-12 angstroms of the L-fucose moiety. The invention compounds are disalicylate, its analogs, and disalicylate-based C-glycoside compounds. The present invention also discloses methods of treating selectin-mediated disorders comprising administering the compounds disclosed.
    • 本发明公开了与某些选择蛋白结合的选择蛋白 - 配体结构模拟物的药物,其中模拟物可能缺乏天然选择配体唾液酸路易斯(sLe x)的唾液酸和/或岩藻糖,但具有 能够模拟选择素识别所必需的结构特征的结构。 特别地,本发明化合物模拟负责选择素介导的细胞粘附的寡糖的关键结构特征。 这些特征包括在L-岩藻糖部分的8-12埃的距离处的唾液酸的羧酸官能度之间的电荷 - 距离 - 配位关系。 本发明化合物是二水杨酸酯,其类似物和二水杨酸酯基的C-糖苷化合物。 本发明还公开了治疗选择素介导的病症的方法,包括给予所公开的化合物。