Small-molecule AT2 receptor agonists

Mathias Hallberg, Colin Sumners, U Muscha Steckelings, Anders Hallberg

Research output: Contribution to journalReviewResearchpeer-review

Abstract

The discovery of the first selective, small-molecule ATR receptor (AT2R) agonist compound 21 (C21) (8) that is now extensively studied in a large variety of in vitro and in vivo models is described. The sulfonylcarbamate derivative 8, encompassing a phenylthiofen scaffold is the drug-like agonist with the highest affinity for the AT2R reported to date (Ki = 0.4 nM). Structure-activity relationships (SAR), regarding different biaryl scaffolds and functional groups attached to these scaffolds and with a particular focus on the impact of various para substituents displacing the methylene imidazole group of 8, are discussed. Furthermore, the consequences of migration of the methylene imidazole group and presumed structural requirements for ligands that are aimed as AT2R agonists (e.g. 8) or AT2R antagonists (e.g. 9), respectively, are briefly addressed. A summary of the pharmacological actions of C21 (8) is also presented.

Original languageEnglish
JournalMedicinal Research Reviews
Volume38
Issue number2
Pages (from-to)602-624
ISSN0198-6325
DOIs
Publication statusPublished - Mar 2018

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Ligands
Pharmaceutical Preparations
imidazole
In Vitro Techniques

Keywords

  • Journal Article
  • Review

Cite this

Hallberg, Mathias ; Sumners, Colin ; Steckelings, U Muscha ; Hallberg, Anders. / Small-molecule AT2 receptor agonists. In: Medicinal Research Reviews. 2018 ; Vol. 38, No. 2. pp. 602-624.
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Hallberg, M, Sumners, C, Steckelings, UM & Hallberg, A 2018, 'Small-molecule AT2 receptor agonists', Medicinal Research Reviews, vol. 38, no. 2, pp. 602-624. https://doi.org/10.1002/med.21449

Small-molecule AT2 receptor agonists. / Hallberg, Mathias; Sumners, Colin; Steckelings, U Muscha; Hallberg, Anders.

In: Medicinal Research Reviews, Vol. 38, No. 2, 03.2018, p. 602-624.

Research output: Contribution to journalReviewResearchpeer-review

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T1 - Small-molecule AT2 receptor agonists

AU - Hallberg, Mathias

AU - Sumners, Colin

AU - Steckelings, U Muscha

AU - Hallberg, Anders

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AB - The discovery of the first selective, small-molecule ATR receptor (AT2R) agonist compound 21 (C21) (8) that is now extensively studied in a large variety of in vitro and in vivo models is described. The sulfonylcarbamate derivative 8, encompassing a phenylthiofen scaffold is the drug-like agonist with the highest affinity for the AT2R reported to date (Ki = 0.4 nM). Structure-activity relationships (SAR), regarding different biaryl scaffolds and functional groups attached to these scaffolds and with a particular focus on the impact of various para substituents displacing the methylene imidazole group of 8, are discussed. Furthermore, the consequences of migration of the methylene imidazole group and presumed structural requirements for ligands that are aimed as AT2R agonists (e.g. 8) or AT2R antagonists (e.g. 9), respectively, are briefly addressed. A summary of the pharmacological actions of C21 (8) is also presented.

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