Synthesis of N-(beta-D-glucopyranosyl) monoamides of dicarboxylic acids as potential inhibitors of glycogen phosphorylase.
O-peracetylated N-(beta-D-glucopyranosyl)imino trimethylphosphorane obtained in situ from 2,3,4,6-tetra-O-acetyl-beta-D-glucopyranosyl azide and PMe3 was reacted with saturated and unsaturated aliphatic and aromatic dicarboxylic acids, or their anhydrides, or monoesters to give the corresponding N-(beta-D-glucopyranosyl) monoamides of dicarboxylic acids or derivatives. The acetyl protecting groups were removed according to the Zemplén protocol to give a series of compounds which showed moderate inhibitory effects against rabbit muscle glycogen phosphorylase b. The best inhibitor was 3-(N-beta-D-glucopyranosyl-carbamoyl)propanoic acid (7) with Ki = 20 microM.
Department of Organic Chemistry, Faculty of Science, University of Debrecen, PO Box 20, H-4010 Debrecen, Hungary.
Katalin
K
Czifrák
Zsuzsa
Z
Hadady
Tibor
T
Docsa
Pál
P
Gergely
Jürgen
J
Schmidt
Ludger
L
Wessjohann
László
L
Somsák
D000577:Amides / Q000138:chemical synthesis* / Q000494:pharmacology; D000818:Animals; D003998:Dicarboxylic Acids / Q000737:chemistry*; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D024982:Glycogen Phosphorylase, Muscle Form / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006860:Hydrogen Bonding; D007700:Kinetics; D015394:Molecular Structure; D011817:Rabbits
D000577:Amides; D003998:Dicarboxylic Acids; D004791:Enzyme Inhibitors; D024982:Glycogen Phosphorylase, Muscle Form