1417819-01-2

Upstream product

• 100-46-9 benzylamine 
• 285991-71-1 4-chloro-1,1-dimethylfuro[3,4-c]pyridine-3(1H)-one 
• 1269593-14-7 4-(2-(dimethylamino)vinyl)-5,5-dimethyl-2-oxo-2,5-dihydrofuran-3-carbonitrile 
• 145887-88-3 1,1-dimethyl-1H,5H-furo[3,4-c]pyridine-3,4-dione 
• 1417818-92-8 4-((E)-2-(dimethylamino)vinyl)-5,5-dimethyl-2-oxo-2,5-dihydrofuran-3-carbonitrile 
• 13332-71-3 4,5,5-trimethyl-2-oxo-2,5-dihydro-furan-3-carbonitrile 

Relevant 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

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.

A serendipitous conversion of enaminolactone nitriles with primary amines: A new synthesis of substituted 2-aminopyridine derivatives

In the course of our studies on Cerpegin analogues synthesis, a serendipitous reactivity of enaminolactone nitrile has been observed. Instead of expecting iminocerpegins, we have gained new class of substituted 2-aminopyridines. The methodology has been applied on a wide range of primary amines, as aliphatic, aromatic, heteroaromatic and also, diamines, hydrazines and chiral amines.