Employing pre-existing functionalized scaffolds to generate focused libraries exemplifies an expedited approach in terms of synthetic feasibility and efficiency. This strategic synthesis is particularly well-suited for scaffolds that are unattainable with DNA-compatible chemical tools. This manuscript utilizes pyridazinone as a paradigmatic scaffold to elucidate the synthetic workflow. Three functionalized pyridazinone reagents were obtained by conventional organic chemistries and then applied to prepare corresponding DNA-encoded libraries (DELs) by robust DNA-compatible reactions and abundant building blocks (BBs), ensuring both diversity and quality in the final libraries. The feasibility of these focused DELs were confirmed by subsequent affinity selection and off-DNA validation against the BRD4 target.

中文翻译：

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轻松合成以哒嗪酮为中心的 DNA 编码文库

使用预先存在的功能化支架来生成重点库，在合成可行性和效率方面体现了一种快速方法。这种策略性合成特别适合 DNA 兼容化学工具无法实现的支架。该手稿利用哒嗪酮作为范例支架来阐明合成工作流程。通过常规有机化学获得三种功能化哒嗪酮试剂，然后通过稳健的DNA相容反应和丰富的构建模块（BB）来制备相应的DNA编码文库（DEL），确保最终文库的多样性和质量。随后的亲和力选择和针对 BRD4 靶标的脱 DNA 验证证实了这些聚焦 DEL 的可行性。