Chemical modification of beta-glucocerebrosidase inhibitor N-octyl-beta-valienamine: synthesis and biological evaluation of N-alkanoyl and N-alkyl derivatives.
Chemical modification of beta-glucocerebrosidase inhibitor N-octyl-beta-valienamine: synthesis and biological evaluation of N-alkanoyl and N-alkyl derivatives.
复制标题
β-葡萄糖脑苷脂酶抑制剂 N-辛基-β-缬烯胺的化学修饰：N-烷酰基和 N-烷基衍生物的合成和生物学评价。
DOI：
10.1016/s0968-0896(98)00143-6
复制
发表时间：
1998
影响因子：
3.5
通讯作者：
J. Inokuchi
中科院分区：
文献类型：
--
作者：
S. Ogawa;Y. Kobayashi;K. Kabayama;M. Jimbo;J. Inokuchi
合成了β-葡萄糖脑苷脂酶抑制剂N-辛基-β-维列胺（3）的N-烷酰基衍生物4a-d和N-烷基衍生物5a-g，以阐明疏水部分在抑制作用中的作用。虽然前者缺乏抑制效力，但后者是强β-葡糖脑苷脂酶抑制剂（参见N-癸基-N-辛基-β-井冈霉烯胺5d：Ki 6.6 ×10− 8 M）。此外，当将N-丁基-N-辛基-β-井冈霉烯胺5a和5d处方给小鼠来源的B16黑色素瘤细胞时，显示出改变GlcCer和GM 3的量，这表明它们可能被引入细胞并影响糖脂生物合成。
Several N-alkanoyl 4a–d and N-alkyl derivatives 5a–g of the potent β-glucocerebrosidase inhibitor N-octyl β-valienamine (3) were synthesized in order to elucidate a role of hydrophobic portion in the inhibitory action. Although the former lacked inhibitory potency, the latter were strong β-glucocerebrosidase inhibitors (cf. N-decyl-N-octyl-β-valienamine 5d: Ki6.6×10−8M). Furthermore, when being prescribed into mouse-derived B16 melanoma cells, N-butyl-N-octyl-β-valienamine 5a and 5d were shown to change the amount of GlcCer and GM3, which suggests that they are possibly introduced into cells and influence glycolipids biosynthesis.