title: Glucose-based spiro-heterocycles as potent inhibitors of glycogen phosphorylase.
abstract: Glucopyranosylidene-spiro-1,4,2-oxathiazoles were prepared in high yields by NBS-mediated spiro-cyclization of the corresponding glucosyl-hydroximothioates. In an effort to synthesize analogous glucopyranosylidene-spiro-1,2,4-oxadiazolines, with a nitrogen atom instead of the sulphur, attempted cyclizations resulted in aromatization of the heterocycle with opening of the pyranosyl ring. Enzymatic measurements showed that some of the glucose-based inhibitors were active in the micromolar range. The 2-naphthyl-substituted 1,4,2-oxathiazole displayed the best inhibition against RMGPb (K(i)=160 nM), among glucose-based inhibitors known to date.
authors: Department of Organic Chemistry, University of Debrecen, POB 20, H-4010 Debrecen, Hungary.
authors: Veronika
authors: V
authors: Nagy
authors: Mahmoud
authors: M
authors: Benltifa
authors: Sébastien
authors: S
authors: Vidal
authors: Eszter
authors: E
authors: Berzsényi
authors: Cathie
authors: C
authors: Teilhet
authors: Katalin
authors: K
authors: Czifrák
authors: Gyula
authors: G
authors: Batta
authors: Tibor
authors: T
authors: Docsa
authors: Pál
authors: P
authors: Gergely
authors: László
authors: L
authors: Somsák
authors: Jean-Pierre
authors: JP
authors: Praly
mesh_terms: D000818:Animals; D005947:Glucose / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D024982:Glycogen Phosphorylase, Muscle Form / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D015394:Molecular Structure; D011817:Rabbits; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D013844:Thiazoles; C540068:glucopyranosylidene-spiro-oxathiazole; D024982:Glycogen Phosphorylase, Muscle Form; D005947:Glucose