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KMID : 0614019950110010149
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Journal of Pharmaceutical Sciences (C.N.U.)
1995 Volume.11 No. 1 p.149 ~ p.158
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Synthesis and Evaluation of Homoazasugars as Glycosidase Inhibitors
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Chi-Huey wong
Louis Provencher/John A. Porco/Jr/Sang-Hun jung/Yi-fong Wang
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Abstract
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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 α-fucosidase from bovine kideney with respective K_i values of 160 nM and 2μM. 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 α-glucosidase and α-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 μM range. Synthesis of homoazasugars structurally related to a disaccharide and a nucleoside is also described.
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