Abstract
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.
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