کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1358010 981307 2014 14 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Glucopyranosylidene-spiro-iminothiazolidinone, a new bicyclic ring system: Synthesis, derivatization, and evaluation for inhibition of glycogen phosphorylase by enzyme kinetic and crystallographic methods
ترجمه فارسی عنوان
گلوکوپیرانوزیلیدین اسپیریمینوتیازولیدینون، یک سیستم حلقه دوچرخه ای جدید: سنتز، مشتق سازی و ارزیابی برای مهار گلیکوژن فسفوریلا توسط روش های سینتیک و کریستالوگرافی آنزیم
موضوعات مرتبط
مهندسی و علوم پایه شیمی شیمی آلی
چکیده انگلیسی

The reaction of thiourea with O-perbenzoylated C-(1-bromo-1-deoxy-β-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 Zemplén 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 = 9 μM) and the 2-naphthoylimino-thiazolidinones (Ki = 10 μM). 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.

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ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bioorganic & Medicinal Chemistry - Volume 22, Issue 15, 1 August 2014, Pages 4028–4041
نویسندگان
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