Abstract
DNA-Encoded Libraries (DEL) represent a promising hit finding strategy for drug discovery. Nonetheless, the available DNA-compatible chemistry remains of limited scope. Nucleophilic aromatic substitution (SNAr) has been extensively used in DEL synthesis but has generally been restricted to highly activated (hetero)arenes. Herein, we report an optimised procedure for SNAr reactions through the use of factorial experimental design (FED) on-DNA using 15% THF as a co-solvent. This method gave conversions of >95% for pyridine and pyrazine scaffolds for 36 secondary cyclic amines. This analysis provides a new DNA-compatible SNAr reaction to produce high yielding libraries. The scope of this reaction on other amines is described. This work identifies challenges for the further development for DNA-compatible SNAr reactions.2009 Elsevier Ltd. All rights reserved.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
