145887-88-3Relevant articles and documents
A new series of N5 derivatives of the 1,1,5-trimethyl furo[3,4-c]pyridine-3,4-dione (cerpegin) selectively inhibits the post-acid activity of mammalian 20S proteasomes
Pham, The Hien,Hovhannisyan, Anna,Bouvier, Dominique,Tian, Lei,Reboud-Ravaux, Michèle,Melikyan, Gagik,Bouvier-Durand, Michelle
, p. 3822 - 3827 (2012)
A large set of N5-derivatives of cerpegin (1,1,5-trimethyl furo[3,4-c]pyridine-3,4-dione) was designed and synthesized in high yields by a simple and handy method using various primary amines for a pyridine cycle synthesis. The effects of 29 derivatives on the three types of catalytic sites of purified mammalian 20S proteasomes (CT-L, T-L and PA) were measured. Most of the new compounds specifically inhibited the PA activity, in the micromolar range. Docking experiments support these results. Moreover, neither calpain I nor cathepsin B were inhibited.
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.
Synthesis and hydrolysis of bicyclic 2-Imino-2,5-dihydrofurans fused to a pyridine ring
Avetisyan,Karapetyan,Tadevosyan
experimental part, p. 1259 - 1261 (2011/02/21)
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