Late-Stage Functionalization by Chan–Lam Amination: Rapid Access to Potent and Selective Integrin Inhibitors

Robinson, Henry; Oatley, Steven; Rowedder, James; Slade, Pawel; Macdonald, Simon; Argent, Stephen; Hirst, Jonathan D.; McInally, Thomas; Moody, Christopher John

Abstract

© 2020 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim A late-stage functionalization of the aromatic ring in amino acid derivatives is described. The key step is a copper-catalysed diversification of a boronate ester by amination (Chan–Lam reaction) that can be carried out on a complex β-aryl-β-amino acid scaffold. This not only considerably extends the substrate scope of amination partners, but also delivers an array of potent and selective integrin inhibitors as potential treatment agents of idiopathic pulmonary fibrosis (IPF). This versatile chemical strategy, which is amenable to high-throughput-array protocols, allows the installation of pharmaceutically valuable heteroaromatic fragments at a late stage by direct coupling to NH heterocycles, leading to compounds with drug-like attributes. It thus constitutes a useful addition to the medicinal chemist's repertoire.

Citation

Robinson, H., Oatley, S., Rowedder, J., Slade, P., Macdonald, S., Argent, S., Hirst, J. D., McInally, T., & Moody, C. J. (2020). Late-Stage Functionalization by Chan–Lam Amination: Rapid Access to Potent and Selective Integrin Inhibitors. Chemistry - A European Journal, 26(34), 7678-7684. https://doi.org/10.1002/chem.202001059

• Journal Article Type: Article
• Acceptance Date: Mar 2, 2020
• Online Publication Date: Mar 4, 2020
• Publication Date: Jun 18, 2020
• Deposit Date: Mar 5, 2020
• Publicly Available Date: Mar 5, 2021
• Journal: Chemistry - A European Journal
• Print ISSN: 0947-6539
• Electronic ISSN: 1521-3765
• Publisher: Wiley
• Peer Reviewed: Peer Reviewed
• Volume: 26
• Issue: 34
• Pages: 7678-7684
• DOI: https://doi.org/10.1002/chem.202001059
• Keywords: General Chemistry
• Public URL: https://nottingham-repository.worktribe.com/output/4093848
• Publisher URL: https://onlinelibrary.wiley.com/doi/abs/10.1002/chem.202001059
• Additional Information: This is the peer reviewed version of the following article: Robinson, H., Oatley, S., Rowedder, J., Slade, P., Macdonald, S., Argent, S., Hirst, J., McInally, T. and Moody, C..J. (2020), Late stage functionalization via Chan‐Lam amination: rapid access to potent and selective integrin inhibitors. Chem. Eur. J.. Accepted Author Manuscript, which has been published in final form at https://doi.org/10.1002/chem.202001059. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions.