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Late-Stage Functionalization by Chan-Lam Amination: Rapid Access to Potent and Selective Integrin Inhibitors
Henry Robinson1, Steven A Oatley2, James E Rowedder3
1School of Chemistry, GSK Carbon Neutral Laboratories for Sustainable Chemistry, University of Nottingham, Jubilee Campus, Triumph Road, Nottingham, NG7 2TU, UK.
Chemistry (Weinheim an Der Bergstrasse, Germany)
|March 5, 2020
Summary
This study introduces a novel late-stage functionalization method for amino acid derivatives using a copper-catalyzed Chan-Lam reaction. This approach yields potent integrin inhibitors, offering new therapeutic potential for idiopathic pulmonary fibrosis (IPF).
Area of Science:
- Organic Chemistry
- Medicinal Chemistry
- Drug Discovery
Background:
- Late-stage functionalization is crucial for developing complex molecules.
- Amino acid derivatives are important pharmaceutical scaffolds.
- Idiopathic pulmonary fibrosis (IPF) requires novel therapeutic agents.
Purpose of the Study:
- To develop a versatile late-stage functionalization strategy for amino acid derivatives.
- To synthesize potent and selective integrin inhibitors for IPF treatment.
- To expand the scope of Chan-Lam amination reactions.
Main Methods:
- Copper-catalyzed Chan-Lam reaction for C-N bond formation.
- Functionalization of β-aryl-β-amino acid scaffolds.
- High-throughput-array protocols for diversification.
Main Results:
- Successful late-stage amination of boronate esters on complex scaffolds.
- Generation of diverse amino acid derivatives with installed heteroaromatic fragments.
- Identification of potent and selective integrin inhibitors.
Conclusions:
- The developed strategy enables efficient late-stage installation of valuable fragments.
- The synthesized compounds show promise as drug candidates for IPF.
- This method offers a valuable tool for medicinal chemists.
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