Synthesis of conformationally constrained benzoylureas as BH3-mimetics?

Organic & Biomolecular Chemistry Pub Date: 2012-05-15 DOI: 10.1039/C2OB25618E

Abstract

The design of small molecules that mimic the BH3 domain and bind to Bcl-2 proteins has emerged as a promising approach to discovering novel anti-cancer therapeutics. We reveal the design and synthesis of conformationally constrained benzoylurea scaffolds as conformational probes. Central to helix mimicry, the intramolecular hydrogen bond in the benzoylurea plays a key role in the pre-organisation of the acyclic substrates for cyclisation via ring closing metathesis, providing efficient access to the constrained mimetics.

Graphical abstract: Synthesis of conformationally constrained benzoylureas as BH3-mimetics
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