445306-52-5

Upstream product

• 13734-41-3 t-Boc-L-valine 
• 259214-70-5 (2S,4R)-4-(7-Methoxy-2-phenyl-quinolin-4-yloxy)-pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester 2-methyl ester 
• 74844-91-0 (2S,4S)-N-tert-butoxycarbonyl-4-hydroxyproline methyl ester 
• 20430-72-2 7-methoxy-2-phenylquinolin-4-ol 
• 737750-26-4 (2S,4R)-4-(7-Methoxy-2-phenyl-quinolin-4-yloxy)-pyrrolidine-2-carboxylic acid methyl ester 

Downstream Products

• 445306-02-5 (2S,4R)-1-((S)-2-tert-Butoxycarbonylamino-3-methyl-butyryl)-4-(7-methoxy-2-phenyl-quinolin-4-yloxy)-pyrrolidine-2-carboxylic acid 

Relevant academic research and scientific papers

β-Amino acid substitutions and structure-based CoMFA modeling of hepatitis C virus NS3 protease inhibitors

In an effort to develop a new type of HCV NS3 peptidomimetic inhibitor, a series of tripeptide inhibitors incorporating a mix of α- and β-amino acids has been synthesized. To understand the structural implications of β-amino acid substitution, the P1, P2, and P3 positions of a potent tripeptide scaffold were scanned and combined with carboxylic acid and acyl sulfonamide C-terminal groups. Inhibition was evaluated and revealed that the structural changes resulted in a loss in potency compared with the α-peptide analogues. However, several compounds exhibited μM potency. Inhibition data were compared with modeled ligand-protein binding poses to understand how changes in ligand structure affected inhibition potency. The P3 position seemed to be the least sensitive position for β-amino acid substitution. Moreover, the importance of a proper oxyanion hole interaction for good potency was suggested by both inhibition data and molecular modeling. To gain further insight into the structural requirements for potent inhibitors, a three-dimensional quantitative structure-activity relationship (3D-QSAR) model has been constructed using comparative molecular field analysis (CoMFA). The most predictive CoMFA model has q2 = 0.48 and rpred2 = 0.68.

A systematic approach to the optimization of substrate-based inhibitors of the hepatitis C virus NS3 protease: Discovery of potent and specific tripeptide inhibitors

The inadequate efficacy and tolerability of current therapies for the infectious liver disease caused by the hepatitis C virus have warranted significant efforts in the development of new therapeutics. We have previously reported competitive peptide inhib