Year: 2025
Type: article
Abstract: Pyridine is a prevalent structural motif in drug molecules, and modifying the pyridine core is a widely utilized strategy for lead optimization in drug discovery. Nitrogen scanning systematically evaluates the effects of varying the nitrogen position within pyridyl isomers, including the extension of the nitrogen atom one or two bonds outside the ring, often resulting in anilines or benzonitriles. This strategy aims to bring the hydrogen‐bonding site closer to the target protein, which can lead to substantial improvements in binding activity. In this study, a synthetic strategy is presented that transforms pyridines into anilines, with the original pyridine nitrogen atom externalized at either the ipso or ortho position. The approach employs a carbene insertion step prior to nitrogen isomerization, preserving the ring size and structural integrity throughout the transformation. This method demonstrates broad applicability, enabling the late‐stage functionalization of a variety of natural products and pharmaceutical agents, and underscores its versatility and potential in drug discovery applications.
Source: ChemistryEurope
Authors: Yun Luo, Jing Dai, Yongchang Wei, Chang Min
Institutions: Wuhan University, Zhongnan Hospital of Wuhan University
Language: English
Subfield: Organic Chemistry
Field: Chemistry
Domain: Physical Sciences
Open Access status: diamond
Awards: G2298069820, G7218170808
OpenAlex ID: W4416225226