1430730-98-5Relevant academic research and scientific papers
4(5)-Aryl-2-C-glucopyranosyl-imidazoles as New Nanomolar Glucose Analogue Inhibitors of Glycogen Phosphorylase
Bokor, éva,Kun, Sándor,Docsa, Tibor,Gergely, Pál,Somsák, László
, p. 1215 - 1219 (2015)
Inhibition of glycogen phosphorylases may lead to pharmacological treatments of diseases in which glycogen metabolism plays an important role: first of all in diabetes, but also in cardiovascular and tumorous disorders. C-(β-d-Glucopyranosyl) isoxazole, pyrazole, thiazole, and imidazole type compounds were synthesized, and the latter showed the strongest inhibition against rabbit muscle glycogen phosphorylase b. Most efficient was 2-(β-d-glucopyranosyl)-4(5)-(2-naphthyl)-imidazole (11b, Ki = 31 nM) representing the best nanomolar glucose derived inhibitor of the enzyme.
Synthetic, enzyme kinetic, and protein crystallographic studies of C-β-D-glucopyranosyl pyrroles and imidazoles reveal and explain low nanomolar inhibition of human liver glycogen phosphorylase
Kantsadi, Anastassia L.,Bokor, éva,Kun, Sándor,Stravodimos, George A.,Chatzileontiadou, Demetra S.M.,Leonidas, Demetres D.,Juhász-Tóth, éva,Szakács, Andrea,Batta, Gyula,Docsa, Tibor,Gergely, Pál,Somsák, László
supporting information, p. 737 - 745 (2016/08/17)
C-β-D-Glucopyranosyl pyrrole derivatives were prepared in the reactions of pyrrole, 2-, and 3-aryl-pyrroles with O-peracetylated β-D-glucopyranosyl trichloroacetimidate, while 2-(β-D-glucopyranosyl) indole was obtained by a cross coupling of O-perbenzylated β-D-glucopyranosyl acetylene with N-tosyl-2-iodoaniline followed by spontaneous ring closure. An improved synthesis of O-perbenzoylated 2-(β-D-glucopyranosyl) imidazoles was achieved by reacting C-glucopyranosyl formimidates with α-aminoketones. The deprotected compounds were assayed with isoforms of glycogen phosphorylase (GP) to show no activity of the pyrroles against rabbit muscle GPb. The imidazoles proved to be the best known glucose derived inhibitors of not only the muscle enzymes (both a and b) but also of the pharmacologically relevant human liver GPa (Ki?=?156 and 26?nM for the 4(5)-phenyl and -(2-naphthyl) derivatives, respectively). An X-ray crystallographic study of the rmGPb-imidazole complexes revealed structural features of the strong binding, and also allowed to explain the absence of inhibition for the pyrrole derivatives.
GLYCOGEN PHOSPHORYLASE INHIBITORS
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, (2013/05/21)
The invention relates to compounds of formula (I) and stereoisomers, tautomers and pharmaceutically acceptable salts thereof and processes for preparing them. In formula (I) X is -CH= or -N= or -N(R") -; Y is -N= or -N(R") -; R is an alkyl group, an aryl group or a heteroaryl group, which groups are unsubstituted or substituted; R' is hydrogen or PG1, R" is hydrogen or PG2, R"' is hydrogen or R'OCH2-; n is an integer of 1 to 3. The invention also relates to pharmaceutical compositions containing these compounds. The compounds according to the invention are glycogen phosphorylase inhibitors and can be used e.g. for the treatment of type 2 diabetes, cardiovascular disorders and tumorous growth.˙
