327084-90-2Relevant academic research and scientific papers
New C4- and C1-derivatives of furo[3,4-c]pyridine-3- ones and related compounds: Evidence for site-specific inhibition of the constitutive proteasome and its immunoisoform
Hovhannisyan, Anna,Pham, The Hien,Bouvier, Dominique,Piroyan, Alexander,Dufau, Laure,Qin, Lixian,Cheng, Yan,Melikyan, Gagik,Reboud-Ravaux, Michèle,Bouvier-Durand, Michelle
supporting information, p. 1571 - 1580 (2014/03/21)
A set of 18 new C4 and C1 derivatives of nor-cerpegin (1,1-dimethyl furo[3,4-c]pyridine-3-one), 6 model compounds (γ- and δ-lactones) and 20 furo- or thieno[2,3-d]-pyrimidine-4-one related compounds were designed and synthesized. Each compound was assayed for inhibition of CT-L, T-L and PA proteolytic activities of 20S constitutive proteasome (c20S). Most performant compounds were also assayed on 20S immunoproteasome (i20S). Compound 10 with a benzylamino group at C4 and dimethylated at C1 of the furopyridine ring was the most efficient PA site-specific inhibitor of the c20S (IC50cPA of 600 nM) without noticeable inhibition of the i20S PA site (iPA). In silico docking assays for 10 at the iPA catalytic site revealed the absence of poses normally observed for this compound and related ones at the constitutive PA site (cPA). The thieno[2,3-d]pyrimidine-4-one 40 was T-L site-specific with a mild inhibition of both c20S and i20S in vitro (IC50cT-L of 9.9 μM and IC50iT-L of 6.7 μM). In silico docking assays of 40 at T-L sites of c20S and i20S revealed almost identical first rank poses in the two types of sites with no possibility left for nucleophilic attack by Thr1 as observed for the fused furopyridine-3-one 10.
Facile approach to the synthesis of substituted thieno[2,3-d]pyrimidin-4- ones
Hovhannisyan, Anna,Aristakesyan, Lilit,Melikyan, Gagik
, p. 253 - 256 (2013/05/09)
Condensation of Gewald's thiophenes substituted with a dimethylaminomethyleneamino group at position 2 with primary amines yields 5/6-aryl-thieno[2,3-d] pyrimidin-4-ones with variable substituents at the N3 position.
A facile, scalable preparation of 4-oxo-4,7-dihydrothieno[2,3-b]pyridine-5-carbonitriles
Tumey, L. Nathan,Bhagirath, Niala,Wu, Biqi,Boschelli, Diane H.
body text, p. 6850 - 6852 (2009/04/07)
We report a new synthesis of thieno[2,3-b]pyridine-5-carbonitriles from 2-aminothiophene-3-carboxylate esters. The key step of the synthesis is a thermally promoted elimination/decarboxylation followed by nucleophilic cyclization to give 4-oxo-4,7-dihydrothieno[2,3-b]pyridine-5-carbonitriles. The reactions proceed in good yield and generally require no chromatographic purification. These compounds are easily transformed in two steps to 4-chloro-2-iodothieno[2,3-b]pyridine-5-carbonitriles which are key intermediates in the synthesis of various kinase inhibitors.
