The present invention provides novel hydroxy piperidine (HP) derivatives having (i) a positive charge at the position corresponding to the anomeric position of a pyranose ring; (ii) a short, flexible linker emanating from the corresponding position of the ring oxygen in a pyranose; and (iii) a lipophilic moiety connected to the linker and pharmaceutically acceptable salts thereof. The linker can be absent if the lipophilic moiety corresponds to a hydrocarbon chain with a linear length of 6 or more carbons. The present invention further provides a method for treating individuals having Gaucher disease by administering the novel HP derivative as “active-site specific chaperones” for the mutant glucocerebrosidase associated with the disease.
本发明提供了新型羟基
哌啶(HP)衍
生物,其具有(i)在
吡喃糖环的异构体相应位置上的正电荷;(ii)从
吡喃糖中环氧的相应位置发出的短柔性连接体;以及(iii)与连接体相连的亲脂分子及其药学上可接受的盐。如果亲脂分子是线性长度为 6 个或更多碳原子的烃链,则可以不使用连接剂。本发明进一步提供了一种治疗戈谢病患者的方法,通过施用新型 HP 衍
生物作为与该疾病相关的突变
葡萄糖脑苷脂酶的 "活性位点特异性伴侣"。