Expedient route to functionalized and water soluble 5-6-5 imidazole-phenyl-thiazole based α-helix mimetics

Christopher G. Cummings, Andrew Hamilton

Research output: Contribution to journalArticle

Abstract

A range of small molecule scaffolds have been shown to act as structural and functional mimics of α-helices by mimicking the i, i+4, and i+7 positions, often found at the interface of PPIs. These molecules, though potent, possess complicating features - either low water solubility, or maintenance of conformation by hydrogen-bonding networks. We have addressed these limitations by developing a scaffold with increased water solubility. Herein we present a rapid synthetic pathway to a library of 56 compounds based on a 5-6-5 scaffold, containing an imidazole-phenyl-thiazole core; the route is flexible and allows rapid installation of different substituents via high-yielding Ullman and Suzuki couplings and Hantsch thiazole syntheses.

Original languageEnglish (US)
Pages (from-to)1663-1668
Number of pages6
JournalTetrahedron
Volume69
Issue number5
DOIs
StatePublished - Feb 4 2013

Fingerprint

Thiazoles
Scaffolds
Solubility
Water
Hydrogen Bonding
Molecules
Maintenance
Conformations
Hydrogen bonds
imidazole

Keywords

  • α-Helix mimetic
  • Fluorescent
  • Hantsch thiazole synthesis
  • Heterocyclic compounds
  • Suzuki coupling

ASJC Scopus subject areas

  • Biochemistry
  • Organic Chemistry
  • Drug Discovery

Cite this

Expedient route to functionalized and water soluble 5-6-5 imidazole-phenyl-thiazole based α-helix mimetics. / Cummings, Christopher G.; Hamilton, Andrew.

In: Tetrahedron, Vol. 69, No. 5, 04.02.2013, p. 1663-1668.

Research output: Contribution to journalArticle

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