2012 Fiscal Year Final Research Report
Medicinal scientific study based on imiosugar C-glycosides mimics
| Project/Area Number |
22590104
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Drug development chemistry
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| Research Institution | Tohoku Pharmaceutical University |
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Principal Investigator |
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| Project Period (FY) |
2010 – 2012
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| Keywords | イミノ糖 / α-グリコシダーゼ阻害剤 / 糖尿病 / L型糖 |
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| Research Abstract |
Glycosidases and glycosyltransferases are involved in a wide range of anabolic and catabolic process, including digestion, the lysosomal catabolism of glycoconjugates, glycoprotein biosynthesis. Hence, modifying or blocking these processes in vivo using inhibitors is a topic of great interest from the therapeutic point of view. Iminosugars are sugars in which the endocyclic oxygen is replaced by a basic nitrogen atom. They are regarded as transition state mimics in certain types of enzyme reactions. This makes the field of iminosugars as carbohydrate mimics an exciting area of research. The asymmetric synthesis of α-1-C-alkyl-arabinoiminofuranoses was achieved by asymmetric allylic alkylation, RCM, and Negishi cross coupling as key reactions. Surprisingly, the L-forms showed a quite potent inhibitory activity toward rat intestinal maltase, while the activities of the D-forms were much weaker. Some of the prepared L-forms showed potent inhibitory activities towards intestinal maltase, with IC50 values comparable to those of commercial drugs such as acarbose, voglibose, and miglitol, which are used in the treatment of type 2 diabetes. Among them, the inhibitory activity towards intestinal sucrase of α-1-C-L-butylarabinoiminofuranose was quite strong towards intestinal sucrase compared to the above commercial drugs.
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[Journal Article] a-1-C-Buty1-1,4-dideoxy-1,4-imino-L-arabinit of as a Second- Generation Iminosugar-Based Oral a-Glucosidase Inhibitor for Improving Postprandial Hyperglycemia2012
Author(s)
Kato, A.; Hayashi, E.; Miyauchi, S.; Adachi, I.; Imahori, T.; Natori, Y.; Yoshimura, Y.; Nash, R. J.; Shimaoka, H.; Nakagome, I.; Koseki, J.; Hirono, S.; Takahata, H
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Journal Title
J. Med. Chem. Cz4
Volume: 55
Pages: 10347-10362
DOI
Peer Reviewed
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[Journal Article] The synthesis and biological evaluation of 1-C-alkyl-L-arabinoiminofuranoses, a novel class of a -glucosidase inhibitors novel class of a -glucosidase inhibitors2011
Author(s)
Natori, Y.; Imahori, T.; Murakami, Natori, Y.; Imahori, T.; Murakami, K.; Yoshimura, Y.; Nakagawa, S.; Kato, A.; Adachi, I.; Takahata, H.
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Journal Title
Bioorg. Med. Chem. Lett.
Volume: 21
Pages: 738-741
Peer Reviewed
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