152963-38-7Relevant academic research and scientific papers
Isosorbide-based peptidomimetics as inhibitors of hepatitis C virus serine protease
Portela, Aline C.,Barros, Thalita G.,Lima, Camilo H. da S.,Dias, Luiza R.S.,Azevedo, Pedro H.R. de A.,Dantas, Anna Sophia C.L.,Mohana-Borges, Ronaldo,Ventura, Gustavo T.,Pinheiro, Sergio,Muri, Estela M.F.
, p. 3661 - 3665 (2017/07/27)
Hepatitis C infection is a cause of chronic liver diseases such as cirrhosis and carcinoma. The current therapy for hepatitis C has limited efficacy and low tolerance. The HCV encodes a serine protease which is critical for viral replication, and few protease inhibitors are currently on the market. In this paper, we describe the synthesis and screening of novel isosorbide-based peptidomimetic inhibitors, in which the compounds 1d, 1e, and 1i showed significant inhibition of the protease activity in vitro at 100?μM. The compound 1e also showed dose-response (IC50?=?36?±?3?μM) and inhibited the protease mutants D168A and V170A at 100?μM, indicating it as a promising inhibitor of the HCV NS3/4A protease. Our molecular modeling studies suggest that the activity of 1e is associated with a change in the interactions of S2 and S4 subsites, since that the increased flexibility favors a decrease in activity against D168A, whereas the appearance of a hydrophobic cavity in the S4 subsite increase the inhibition against V170A strain.
Synthesis of New Chiral Auxiliaries Derived From Isosorbide
Tamion, R.,Marsais, F.,Ribereau, P.,Queguiner, G.,Abenhaim, D.,et al.
, p. 1879 - 1890 (2007/10/02)
Synthesis of both monobenzenesulfonates of isosorbide (1,4:3,6-dianhydrosorbitol) was regioselectively achieved in high yields via a three-step sequence.These monoesters were O-alkylated before being reacted with various primary amines to give the corresponding amino esters.The full control of regioselectivity led either to the exo-exo or endo-endo isomers.In an independent pathway, isosorbide derived amino ethers and amino alcohols with both amino and hydroxy functions in the endo position, were synthesized from isosorbide in a four-step procedure including selective monobenzylation, tosylation, substitution by amines and debenzylation.
