Synthesis of N-(beta-D-glucopyranosyl)- and N-(2-acetamido-2-deoxy-beta-D-glucopyranosyl) amides as inhibitors of glycogen phosphorylase.
2,3,4,6-Tetra-O-acetyl-beta-D-glucopyranosyl- and 2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-beta-D-glucopyranosyl azides were transformed into the corresponding per-O-acetylated N-(beta-D-glycopyranosyl) amides via a PMe(3) mediated Staudinger protocol (generation of N-(beta-D-glycopyranosyl)imino-trimethylphosphoranes followed by acylation with carboxylic acids, acid chlorides or anhydrides). The deprotected compounds obtained by Zemplén deacetylation were evaluated as inhibitors of rabbit muscle glycogen phosphorylase b. The best inhibitor of this series has been N-(beta-D-glucopyranosyl) 3-(2-naphthyl)-propenoic amide (K(i)=3.5microM).
Györgydeák
Zoltán
Z
Department of Organic Chemistry, Faculty of Science, PO Box 20, H-4010 Debrecen, Hungary.
Hadady
Zsuzsa
Z
Felföldi
Nóra
N
Krakomperger
Attila
A
Nagy
Veronika
V
Tóth
Marietta
M
Brunyánszki
Attila
A
Docsa
Tibor
T
Gergely
Pál
P
Somsák
László
L
D000577:Amides / Q000138:chemical synthesis* / Q000494:pharmacology; D000818:Animals; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology; D005947:Glucose / Q000138:chemical synthesis* / Q000494:pharmacology; D024982:Glycogen Phosphorylase, Muscle Form / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009539:Nicotinic Acids / Q000138:chemical synthesis* / Q000494:pharmacology; D011817:Rabbits
D000577:Amides; D004791:Enzyme Inhibitors; D009539:Nicotinic Acids; D024982:Glycogen Phosphorylase, Muscle Form; D005947:Glucose