Convenient synthesis and evaluation of enzyme inhibitory activity of several N-alkyl-, N-phenylalkyl, and cyclic isourea derivatives of 5a-carba-alpha-DL-fucopyranosylamine

Seiichiro Ogawa; Makiko Mori; Goichi Takeuchi; Fuminao Doi; Maiko Watanabe; Yuko Sakata

doi:10.1016/s0960-894x(02)00627-3

Convenient synthesis and evaluation of enzyme inhibitory activity of several N-alkyl-, N-phenylalkyl, and cyclic isourea derivatives of 5a-carba-alpha-DL-fucopyranosylamine

Bioorg Med Chem Lett. 2002 Oct 21;12(20):2811-4. doi: 10.1016/s0960-894x(02)00627-3.

Authors

Seiichiro Ogawa¹, Makiko Mori, Goichi Takeuchi, Fuminao Doi, Maiko Watanabe, Yuko Sakata

Affiliation

¹ Department of Life Sciences and Informatics, Faculty of Science and Technology, Keio University, Hiyoshi, Kohoku-ku, Yokohama, Japan. ogawa@bio.keio.ac.jp

PMID: 12270152
DOI: 10.1016/s0960-894x(02)00627-3

Abstract

Convenient synthesis and chemical modification of the potent alpha-L-fucosidase inhibitor, 5a-carba-alpha-DL-fucopyranosylamine (1), are described. Among seven N-substituted and three cyclic isourea derivatives newly prepared, the N-octyl derivative was found to be the strongest inhibitor of alpha-L-fucosidase (bovine kidney) more potent (K(i)=0.016 microM) than deoxyfuconojirimycin (K(i)=0.031 microM) with p-nitrophenyl-alpha-L-fucopyranoside as the substrate.

MeSH terms

Animals
Cattle
Enzyme Inhibitors / chemical synthesis*
Enzyme Inhibitors / pharmacology*
Fucose / analogs & derivatives
Fucose / chemical synthesis*
Fucose / pharmacology*
Glycoside Hydrolases / antagonists & inhibitors
Indicators and Reagents
Kidney / drug effects
Molecular Conformation
Structure-Activity Relationship
alpha-L-Fucosidase / antagonists & inhibitors

Substances

5a-carbafucopyranosylamine
Enzyme Inhibitors
Indicators and Reagents
Fucose
Glycoside Hydrolases
alpha-L-Fucosidase