KHAN, M. AMIN,坎恩 艾姆,坎恩 艾姆,WOOD, PAUL L.,伍德 保罗,伍德 保羅,GOODENOWE, DAYAN,古登诺威 戴炎,古登諾威 戴炎,MANKIDY, RISHIKESH,曼奇迪 瑞西克奇,曼奇迪 瑞西克奇,AHIAHONU, PEARSON,亚希霍努 皮尔森,亞希霍努 皮爾森
申请号：
TW098143152
公开号：
TWI475989B
申请日:
2009.12.16
申请国别(地区):
TW
年份:
2015
代理人:
摘要：
Described herein are routes of synthesis and therapeutic uses of 1-alkyl, 2-acyl glycerol derivatives of formula I:which when administered to mammalian biological systems result in increased cellular concentrations of specific sn-2 substituted ethanolamine plasmalogens independent of the ether lipid synthesis capacity of the system. Elevating levels of the specific sn-2 substituted species in this way can cause lowering of membrane cholesterol levels and the lowering of amyloid secretion. These compounds can be used for the treatment or prevention of diseases of aging associated with increased membrane cholesterol, increased amyloid, and decreased plasmalogen levels, such as neurodegeneration (including Alzheimer’s disease, Parkinson’s disease and age-related macular degeneration), cognitive impairment, dementia, cancer (e.g. prostate, lung, breast, ovarian, and kidney cancers), osteoporosis, bipolar disorder and vascular diseases (such as atherosclerosis, hypercholesterolemia).在此描述者為式I之1-烷基、2-醯基甘油衍生物的合成路徑和治療用途,其當投予至哺乳動物生物系統時,導致與系統的醚脂質合成能力無關之特定sn-2取代之乙醇胺縮醛磷脂類的細胞濃度增加。該特定sn-2取代之種類之以此方式的提高含量可導致膜膽固醇含量之降低和類澱粉蛋白分泌之降低。這些化合物可用於治療或預防與膜膽固醇增加、類澱粉蛋白增加和縮醛磷脂含量減少有關之老化疾病,例如神經退化(包括阿茲海默症、帕金森氏病症和年齡相關性黃斑變性)、認知損傷、癡呆症、癌(例如攝護腺、肺、乳房、卵巢和腎癌)、骨質疏鬆症、躁鬱症和血管疾病(諸如動脈硬化、高膽固醇血症)。
