title: The synthesis and biological evaluation of 1-C-alkyl-L-arabinoiminofuranoses, a novel class of α-glucosidase inhibitors.
abstract: The asymmetric synthesis of 1-C-alkyl-l-arabinoiminofuranoses 1 was achieved by asymmetric allylic alkylation (AAA), ring closing metathesis (RCM), and Negishi cross coupling as key reactions. Some of the prepared compounds showed potent inhibitory activities towards intestinal maltase, with IC(50) 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 (IC(50)=0.032μM) towards intestinal sucrase of 1c was quite strong compared to the above commercial drugs.
authors.affiliation: Faculty of Pharmaceutical Sciences, Tohoku Pharmaceutical University, Sendai 981-8558, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Natori
authors.forename: Tatsushi
authors.initials: T
authors.lastname: Imahori
authors.forename: Keiichi
authors.initials: K
authors.lastname: Murakami
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Yoshimura
authors.forename: Shinpei
authors.initials: S
authors.lastname: Nakagawa
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kato
authors.forename: Isao
authors.initials: I
authors.lastname: Adachi
authors.forename: Hiroki
authors.initials: H
authors.lastname: Takahata
mesh_terms: D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000201:enzymology; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D065089:Glycoside Hydrolase Inhibitors; D006801:Humans; D007004:Hypoglycemic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D050113:Imino Furanoses / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D051381:Rats; D000520:alpha-Glucosidases / Q000378:metabolism*
chemical_list: D004791:Enzyme Inhibitors; D065089:Glycoside Hydrolase Inhibitors; D007004:Hypoglycemic Agents; D050113:Imino Furanoses; D000520:alpha-Glucosidases