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Scaffold Remodelling of Diazaspirotricycles Enables Synthesis of Diverse sp³ -Rich Compounds With Distinct Phenotypic Effects.

ABSTRACT: A 'top down' scaffold remodelling approach to library synthesis was applied to spirotricyclic ureas prepared by a complexity-generating oxidative dearomatisation. Eighteen structurally-distinct, sp³ -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.

SUBMITTER: Okolo EA

PROVIDER: S-EPMC10946999 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature

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Scaffold Remodelling of Diazaspirotricycles Enables Synthesis of Diverse sp3 -Rich Compounds With Distinct Phenotypic Effects.

Okolo Ephraim A EA Pahl Axel A Sievers Sonja S Pask Christopher M CM Nelson Adam A Marsden Stephen P SP

Chemistry (Weinheim an der Bergstrasse, Germany) 20230322 26

A 'top down' scaffold remodelling approach to library synthesis was applied to spirotricyclic ureas prepared by a complexity-generating oxidative dearomatisation. Eighteen structurally-distinct, sp3 -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 lib ...[more]

PMID: 36722618

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