α-氟化单酮和二酮的反应性揭示了它们作为可逆共价药物亲电战斗部的潜力

IF 2.7 3区化学 Q2 CHEMISTRY, ORGANIC

European Journal of Organic Chemistry Pub Date : 2025-09-26 DOI:10.1002/ejoc.202500380

Yossi Zafrani , Ido Michael Herzog , Eliav Blum , Shlomi Elias , Sigal Saphier , Ishay Columbus

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引用次数: 0

摘要

氟化二酮（fdk）是亲电基团，具有独特的分子特性，使其具有潜在的可逆性和多面共价弹头，可用于药物设计。为了进一步探索这一潜力，研究了各种氟化单酮（fmk）和fdk在相关亲核氨基酸丝氨酸、半胱氨酸和赖氨酸存在下的多组分平衡系统。利用19f - NMR和13C- NMR对这些平衡体系进行了研究，结果表明，对于半胱氨酸和赖氨酸，所研究的大多数fmk和fdk都可能作为可逆共价药物的亲电弹头。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

The Reactivity of α‐Fluorinated Mono‐ and Diketones Uncovers their Potential as Electrophilic Warheads for Reversible Covalent Drugs

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The Reactivity of α‐Fluorinated Mono‐ and Diketones Uncovers their Potential as Electrophilic Warheads for Reversible Covalent Drugs

Fluorinated diketones (FDKs) are electrophilic moieties holding unique molecular properties that make them potential reversible and multifaceted covalent warheads for drug design. To further explore this potential, the multicomponent equilibrium systems of various fluorinated monoketones (FMKs) and FDKs in the presence of the relevant nucleophilic amino acids serine, cysteine, and lysine are studied. These equilibrium systems are investigated using ¹⁹ F‐ and ¹³C‐ NMR spectroscopy, and reveal that for both cysteine and lysine most of the FMKs and FDKs studied may potentially serve as electrophilic warheads for reversible covalent drugs.

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来源期刊

European Journal of Organic Chemistry 化学-有机化学

CiteScore

5.40

自引率

3.60%

发文量

752

审稿时长

1 months

期刊介绍： The European Journal of Organic Chemistry (2019 ISI Impact Factor 2.889) publishes Full Papers, Communications, and Minireviews from the entire spectrum of synthetic organic, bioorganic and physical-organic chemistry. It is published on behalf of Chemistry Europe, an association of 16 European chemical societies. The following journals have been merged to form two leading journals, the European Journal of Organic Chemistry and the European Journal of Inorganic Chemistry: Liebigs Annalen Bulletin des Sociétés Chimiques Belges Bulletin de la Société Chimique de France Gazzetta Chimica Italiana Recueil des Travaux Chimiques des Pays-Bas Anales de Química Chimika Chronika Revista Portuguesa de Química ACH—Models in Chemistry Polish Journal of Chemistry.