Late stage functionalization via Chan-Lam amination: rapid access to potent and selective integrin inhibitors

Chemistry : a European Journal
Henry RobinsonChristopher John Moody

Abstract

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, and not only considerably extends the substrate scope of amination partners, but also delivers an array of potent and selective integrin inhibitors as potential treatments of idiopathic pulmonary fibrosis (IPF). This versatile chemistry 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 the NH heterocycles, leading to compounds with drug-like attributes, and is a useful addition to the medicinal chemist's repertoire.

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Citations

Jul 30, 2020·Dalton Transactions : an International Journal of Inorganic Chemistry·Xianqiang HuangJikun Li
May 19, 2020·Journal of Chemical Information and Modeling·Ellen E GuestJonathan D Hirst

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