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

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 ß-aryl-ß-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.

A thematic analysis of disinformation in gender-affirming healthcare bans in the United States.

CONTEXT: Bans on gender-affirming care (GAC) for transgender and gender-expansive (TGE) people are grounded in scientific disinformation and have been challenged in American courts. METHODS: Five legal filings by state officials in defense of GAC restriction from initial litigation were analyzed using reflexive thematic analysis. Themes and subthemes of disinformation were identified after review and analysis of these filings. FINDINGS: Five themes of disinformation emerged: False and misleading claims about (1) gender dysphoria and gender identity, (2) the evidence regarding GAC, (3) standard practice of GAC, (4) the safety of GAC, and finally, (5) rejection of medical authority. These themes were well represented across the analyzed documents. CONCLUSIONS: The five disinformation themes and subthemes have been noted in lower courts, but have seen some purchase in appellate courts, suggesting that medical disinformation in law may have far-reaching consequences for medical policy.