Hydroxy piperidine derivatives to treat gaucher disease
申请人:Fan Jian-Qiang
公开号:US20050130972A1
公开(公告)日:2005-06-16
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"。
Hollis W. Gary, Jr., Smith Philip L., Hood David K., Cook Stacie M., J. Org. Chem, 59 (1994) N 12, S 3485-3486
作者:Hollis W. Gary, Jr., Smith Philip L., Hood David K., Cook Stacie M.
DOI:——
日期:——
GOESSINGER, E., MONATSH. CHEM., 1982, 113, N 3, 339-354
作者:GOESSINGER, E.
DOI:——
日期:——
HYDROXY PIPERIDINE DERIVATIVES TO TREAT GAUCHER DISEASE