Scaffold Remodelling of Diazaspirotricycles Enables Synthesis of Diverse sp 3 ‐Rich Compounds With Distinct Phenotypic Effects

A ‘top down’ scaffold remodelling approach to library synthesis was applied to spirotricyclic ureas prepared by a complexity‐generating oxidative dearomatisation. Eighteen structurally‐distinct, sp 3 ‐rich scaffolds were accessed from the parent tricycle through ring addition, cleavage and expansion...

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Bibliographic Details
Published in:Chemistry : a European journal Vol. 29; no. 26; p. e202203992
Main Authors: Okolo, Ephraim A., Pahl, Axel, Sievers, Sonja, Pask, Christopher M., Nelson, Adam, Marsden, Stephen P.
Format: Journal Article
Language:English
Published: Germany 08.05.2023
Subjects:
Gene Library
Small Molecule Libraries - chemistry
phenotypic screening
library synthesis
molecular diversity
dearomatisation
ISSN:0947-6539, 1521-3765
Online Access:Get full text
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Summary:A ‘top down’ scaffold remodelling approach to library synthesis was applied to spirotricyclic ureas prepared by a complexity‐generating oxidative dearomatisation. Eighteen structurally‐distinct, sp 3 ‐rich scaffolds were accessed from the parent tricycle through ring addition, cleavage and expansion strategies. Biological screening of a small compound library based on these scaffolds using the cell‐painting assay demonstrated distinctive phenotypic responses engendered by different library members, illustrating the functional as well as structural diversity of the compounds.
ISSN:0947-6539
1521-3765
DOI:10.1002/chem.202203992