DNA-Compatible Synthesis of Amidine Pharmacophores via Late-Stage Amine Modification

IF 4.6 1区化学 Q1 CHEMISTRY, ORGANIC

Organic Chemistry Frontiers Pub Date : 2025-07-03 DOI:10.1039/d5qo00818b

Huihong Wang, Jiale Huang, Xianfu Fang, Huilin Liao, Gong Zhang, Wei Fang, Yizhou Li

引用次数: 0

Abstract

Amidines are prevalent pharmacophores that are widely utilized in medicinal chemistry. The selective modification of amines within DNA-encoded libraries (DELs) offers a direct approach to constructing these pharmacophores, thereby enhancing library structural diversity. Herein, we report a hydroxylamine-mediated conversion of amino groups to amidines, based on our ongoing development of in situ conversion strategies. This method enables efficient coupling with diverse nitriles and demonstrates broad tolerance to protecting groups. Furthermore, we successfully applied this approach to the on-DNA synthesis of iNOS and PAD4 inhibitors.

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通过后期胺修饰的胺类药物载体的dna相容合成

脒类是一种在药物化学中广泛应用的药效团。dna编码文库（DELs）中胺的选择性修饰为构建这些药效团提供了一种直接的方法，从而增强了文库结构的多样性。在此，我们报告了羟胺介导的氨基到脒的转化，基于我们正在进行的原位转化策略的发展。这种方法能够与不同的腈进行有效的偶联，并且对保护基团具有广泛的耐受性。此外，我们成功地将这种方法应用于dna上iNOS和PAD4抑制剂的合成。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Organic Chemistry Frontiers CHEMISTRY, ORGANIC-

CiteScore

7.90

自引率

11.10%

发文量

686

审稿时长

1 months

期刊介绍： Organic Chemistry Frontiers is an esteemed journal that publishes high-quality research across the field of organic chemistry. It places a significant emphasis on studies that contribute substantially to the field by introducing new or significantly improved protocols and methodologies. The journal covers a wide array of topics which include, but are not limited to, organic synthesis, the development of synthetic methodologies, catalysis, natural products, functional organic materials, supramolecular and macromolecular chemistry, as well as physical and computational organic chemistry.