4ctn

Publication Abstract from PubMed

The reaction of thiourea with O-perbenzoylated C-(1-bromo-1-deoxy-beta-d-glucopyranosyl)formamide gave the new anomeric spirocycle 1R-1,5-anhydro-d-glucitol-spiro-[1,5]-2-imino-1,3-thiazolidin-4-one. Acylation and sulfonylation with the corresponding acyl chlorides (RCOCl or RSO2Cl where R=tBu, Ph, 4-Me-C6H4, 1- and 2-naphthyl) produced the corresponding 2-acylimino- and 2-sulfonylimino-thiazolidinones, respectively. Alkylation by MeI, allyl-bromide and BnBr produced mixtures of the respective N-alkylimino- and N,N'-dialkyl-imino-thiazolidinones, while reactions with 1,2-dibromoethane and 1,3-dibromopropane furnished spirocyclic 5,6-dihydro-imidazo[2,1-b]thiazolidin-3-one and 6,7-dihydro-5H-thiazolidino[3,2-a]pyrimidin-3-one, respectively. Removal of the O-benzoyl protecting groups by the Zemplen protocol led to test compounds most of which proved micromolar inhibitors of rabbit muscle glycogen phosphorylase b (RMGPb). Best inhibitors were the 2-benzoylimino- (Ki=9muM) and the 2-naphthoylimino-thiazolidinones (Ki=10muM). Crystallographic studies of the unsubstituted spiro-thiazolidinone and the above most efficient inhibitors in complex with RMGPb confirmed the preference and inhibitory effect that aromatic (and especially 2-naphthyl) derivatives show for the catalytic site promoting the inactive conformation of the enzyme.

Glucopyranosylidene-spiro-iminothiazolidinone, a new bicyclic ring system: Synthesis, derivatization, and evaluation for inhibition of glycogen phosphorylase by enzyme kinetic and crystallographic methods.,Czifrak K, Pahi A, Deak S, Kiss-Szikszai A, Kover KE, Docsa T, Gergely P, Alexacou KM, Papakonstantinou M, Leonidas DD, Zographos SE, Chrysina ED, Somsak L Bioorg Med Chem. 2014 Aug 1;22(15):4028-41. doi: 10.1016/j.bmc.2014.05.076. Epub , 2014 Jun 16. PMID:25009003^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.