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KMID : 0614019950110010149
Journal of Pharmaceutical Sciences (C.N.U.)
1995 Volume.11 No. 1 p.149 ~ p.158
Synthesis and Evaluation of Homoazasugars as Glycosidase Inhibitors
Chi-Huey wong
Louis Provencher/John A. Porco/Jr/Sang-Hun jung/Yi-fong Wang
Abstract
In an effort to develop transition-state mimetics of the glycosidase-catalyzed reaction, five- and six-membered azasugars and their homo-analogs were prepared and tested as inhibitors of glycosidases. Inhibition studies indicate that the fucosyl cationlike, five-membered imine 1 and its reduced form 2 are potent inhibitors of ¥á-fucosidase from bovine kideney with respective K_i values of 160 nM and 2¥ìM. The five-membered homoaminoazasugar 3 is also a potent inhibitor of the enzyme (K_i=1.9¡¿10^-6M), while the glucose and mannose-like six-membered homoaminoazasugars 4 and 5 are less potent than the corresponding 1-deoxyazasugars as inhibitors of ¥á-glucosidase and ¥á-mannosidase, respectively. The primary amino group was placed in an attempt to introduce additional electrostatic interactions in the active site. The inhibitory activities are, however, in the high ¥ìM range. Synthesis of homoazasugars structurally related to a disaccharide and a nucleoside is also described.
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