Design and Synthesis of 5a-Carbaglycopyranosylamime Glycosidase Inhibitors

Author(s): Seiichiro Ogawa , Miki Kanto .

Journal Name: Current Topics in Medicinal Chemistry

Volume 9 , Issue 1 , 2009

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5a-Carba-α-D-glucopyranosylamine, validamine, and analogous compounds valienamine and valiolamine, have proved to be important lead compounds for development of clinically useful medicines, including the very strong α- glucosidase inhibitor, voglibose, N-(1,3-dihydroxyprop-2-yl)valiolamine, now used widely as a clinically important antidiabetic agent. In this review, we describe recent advances in development of glycosidase inhibitors on the basis of the ground-state mimics of the postulated glycopyranosyl cation, considered to be formed during hydrolysis of glycopyranosides, and introduce a new type of highly potent α-fucosidase inhibitor, 5a-carba-α-L-fucopyranosylamine, α- fuco validamine. Interestingly, the corresponding β-anomer, and in particular its D-enantiomer, has been shown to possess very strong cross-inhibitory activity toward β-galactosidase and β-glucosidase. Structure and inhibitory activity relationships concerning these α,β-fuco derivatives, as well as parent α,β-galacto validamines are discussed here with reference to our results.

Keywords: Glycosidase, 5a-Carbaglycopyranosylamime, Inhibitors, validamine, antidiabetic agent, cross-inhibitory activity

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Article Details

Year: 2009
Page: [58 - 75]
Pages: 18
DOI: 10.2174/156802609787354324

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