285991-71-1Relevant articles and documents
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
, 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.
'One-pot' four-step synthesis of cerpegin
Lazaar, Jalal,Hoarau, Christophe,Mongin, Florence,Trécourt, Francois,Godard, Alain,Quéguiner, Guy,Marsais, Francis
, p. 3811 - 3813 (2007/10/03)
Cerpegin (1) was synthesized through a 'one-pot' reaction in 71% overall yield. Lithiation of commercially available 2-methoxynicotinic acid (2) as its lithium salt using LTMP, followed by addition of acetone at low temperature and a specific acidic treatment of the intermediate 3 thus obtained, gave the 1,1-dimethyl-3,4-dioxo-1,3,4,5-tetrahydrofuro[3,4-c]pyridine (4). The latter was finally selectively alkylated using methyl iodide and caesium carbonate to afford cerpegin (1).
A short total synthesis of cerpegin by intramolecular hetero Diels-Alder cycloaddition reaction of an acetylene tethered pyrimidine
Tarasov, Evgeniy V.,Henckens, Anja,Ceulemans, Erik,Dehaen, Wim
, p. 625 - 626 (2007/10/03)
The electron poor 4,6-dichloropyrimidine-5-carbaldehyde, which is readily available, is used as a starting material for the synthesis of fused 2-chloropyridines. Chlorination transforms the aldehyde into the corresponding acid chloride, which can be functionalized with acetylene tethers. Intramolecular hetero Diels-Alder reactions at elevated temperatures afford the fused pyridines in varying yield. This reaction sequence was applied to the total synthesis of cerpegin.
