Deliberately losing control of C-H activation processes in the design of small molecule fragment arrays targeting peroxisomal metabolism

Tareque, Raysa Kahn, Hassell-Hart, Storm, Krojer, Tobias, Bradley, Anthony, Velupillai, Srikannathasan, Talon, Romain, Fairhead, Michael, Day, Iain J, Bala, Kamlesh, Felix, Robert, Kemmitt, Paul, Brennan, Paul, von Delft, Frank, Díaz Sáez, Laura, Spencer, John and Huber, Kilian (2020) Deliberately losing control of C-H activation processes in the design of small molecule fragment arrays targeting peroxisomal metabolism. ChemMedChem. ISSN 1860-7179

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Abstract

Combined photochemical arylation, “nuisance effect” (S N Ar) reaction sequences have been employed in the design of small arrays for immediate deployment in medium throughput X‐ray protein‐ligand structure determination. Reactions have been deliberately let “out of control,” in terms of selectivity; for example the ortho‐arylation of 2‐phenylpyridine gave five products resulting from mono‐, bis‐ arylations combined with S N Ar processes. As a result, a number of crystallographic hits against NUDT7, a key peroxisomal CoA ester hydrolase, have been identified.

Item Type: Article
Keywords: array, catalysis, fragment based drug discovery, hydrolase, palladium
Schools and Departments: School of Life Sciences > Biochemistry
School of Life Sciences > Chemistry
SWORD Depositor: Mx Elements Account
Depositing User: Mx Elements Account
Date Deposited: 21 Aug 2020 08:56
Last Modified: 21 Aug 2020 09:18
URI: http://sro.sussex.ac.uk/id/eprint/93192

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