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• W3163765390 endingPage "116218" @default.
• W3163765390 startingPage "116218" @default.
• W3163765390 abstract "DNA-encoded libraries (DEL) represent a powerful technology for generating compound collections for drug discovery campaigns, that have allowed for the selection of many hit compounds over last three decades. However, the application of split-and-pool combinatorial methodologies, as well as the limitation imposed by DNA-compatible chemistry, has often brought to a limited exploration of the chemical space, with an over-representation of flat aromatic or peptide-like structures, whereas a higher scaffold complexity is generally associated with a more successful biological activity of the library. In this context, the application of Diversity-Oriented Synthesis, capable of creating sp3-rich molecular entities even starting from simple flat building blocks, can represent an efficient strategy to significantly broaden the chemical space explored by DELs. In this review, we present selected examples of DNA-compatible complexity-generating reactions that can be applied for the generation of DNA-encoded DOS libraries, including: (i) multicomponent reactions; (ii) C-H/C-X functionalization; (iii) tandem approaches; (iv) cycloadditions; (v) reactions introducing privileged elements. Also, selected case studies on the generation of DELs with high scaffold diversity are discussed, reporting their application in drug discovery programs." @default.
• W3163765390 created "2021-05-24" @default.
• W3163765390 creator A5041407933 @default.
• W3163765390 creator A5051937105 @default.
• W3163765390 creator A5072369338 @default.
• W3163765390 date "2021-07-01" @default.
• W3163765390 modified "2023-09-27" @default.
• W3163765390 title "Diversity-oriented synthesis as a tool to expand the chemical space of DNA-encoded libraries" @default.
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