title: Synthesis of variously coupled conjugates of D-glucose, 1,3,4-oxadiazole, and 1,2,3-triazole for inhibition of glycogen phosphorylase.
abstract: 5-(O-Perbenzoylated-β-D-glucopyranosyl)tetrazole was obtained from O-perbenzoylated-β-D-glucopyranosyl cyanide by Bu(3)SnN(3) or Me(3)SiN(3)-Bu(2)SnO. This tetrazole was transformed into 5-ethynyl- as well as 5-chloromethyl-2-(O-perbenzoylated-β-D-glucopyranosyl)-1,3,4-oxadiazoles by acylation with propiolic acid-DCC or chloroacetyl chloride, respectively. The chloromethyl oxadiazole gave the corresponding azidomethyl derivative on treatment with NaN(3). These compounds were reacted with several alkynes and azides under Cu(I) catalysed cycloaddition conditions to give, after removal of the protecting groups by the Zemplén protocol, β-D-glucopyranosyl-1,3,4-oxadiazolyl-1,2,3-triazole, β-D-glucopyranosyl-1,2,3-triazolyl-1,3,4-oxadiazole, and β-D-glucopyranosyl-1,3,4-oxadiazolylmethyl-1,2,3-triazole type compounds. 5-Phenyltetrazole was also transformed under the above conditions into a series of aryl-1,3,4-oxadiazolyl-1,2,3-triazoles, aryl-1,2,3-triazolyl-1,3,4-oxadiazoles, and aryl-1,3,4-oxadiazolylmethyl-1,2,3-triazoles. The new compounds were assayed against rabbit muscle glycogen phosphorylase b and the best inhibitors had inhibition constants in the upper micromolar range (2-phenyl-5-[1-(β-D-glucopyranosyl)-1,2,3-triazol-4-yl]-1,3,4-oxadiazole 36: K(i)=854μM, 2-(β-D-glucopyranosyl)-5-[1-(naphthalen-2-yl)-1,2,3-triazol-4-yl]-1,3,4-oxadiazole 47: K(i)=745μM).
authors.affiliation: Department of Organic Chemistry, University of Debrecen, POB 20, H-4010 Debrecen, Hungary.
authors.forename: Sándor
authors.initials: S
authors.lastname: Kun
authors.forename: Gergo Z
authors.initials: GZ
authors.lastname: Nagy
authors.forename: Marietta
authors.initials: M
authors.lastname: Tóth
authors.forename: Laura
authors.initials: L
authors.lastname: Czecze
authors.forename: Albert Nguyen
authors.initials: AN
authors.lastname: Van Nhien
authors.forename: Tibor
authors.initials: T
authors.lastname: Docsa
authors.forename: Pál
authors.initials: P
authors.lastname: Gergely
authors.forename: Maria-Despoina
authors.initials: MD
authors.lastname: Charavgi
authors.forename: Paraskevi V
authors.initials: PV
authors.lastname: Skourti
authors.forename: Evangelia D
authors.initials: ED
authors.lastname: Chrysina
authors.forename: Tamás
authors.initials: T
authors.lastname: Patonay
authors.forename: László
authors.initials: L
authors.lastname: Somsák
mesh_terms: D000480:Alkynes / Q000737:chemistry; D000818:Animals; D001386:Azides / Q000737:chemistry; D002384:Catalysis; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000503:physiopathology; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D005947:Glucose / Q000737:chemistry; D006001:Glycoconjugates / Q000138:chemical synthesis* / Q000494:pharmacology; D024982:Glycogen Phosphorylase, Muscle Form / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D010069:Oxadiazoles / Q000737:chemistry; D010763:Phosphorylase b / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011422:Propionates / Q000737:chemistry; D011817:Rabbits; D014230:Triazoles / Q000737:chemistry
chemical_list: D000480:Alkynes; D001386:Azides; D004791:Enzyme Inhibitors; D006001:Glycoconjugates; D010069:Oxadiazoles; D011422:Propionates; D014230:Triazoles; D024982:Glycogen Phosphorylase, Muscle Form; D010763:Phosphorylase b; D005947:Glucose; C011537:propiolic acid