Small-molecule AT2 receptor agonists

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

Publikation: Bidrag til tidsskriftReviewForskningpeer review

Resumé

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.

OriginalsprogEngelsk
TidsskriftMedicinal Research Reviews
Vol/bind38
Udgave nummer2
Sider (fra-til)602-624
ISSN0198-6325
DOI
StatusUdgivet - mar. 2018

Fingeraftryk

Ligands
Pharmaceutical Preparations
imidazole
In Vitro Techniques

Citer dette

Hallberg, Mathias ; Sumners, Colin ; Steckelings, U Muscha ; Hallberg, Anders. / Small-molecule AT2 receptor agonists. I: Medicinal Research Reviews. 2018 ; Bind 38, Nr. 2. s. 602-624.
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Hallberg, M, Sumners, C, Steckelings, UM & Hallberg, A 2018, 'Small-molecule AT2 receptor agonists', Medicinal Research Reviews, bind 38, nr. 2, s. 602-624. https://doi.org/10.1002/med.21449

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

I: Medicinal Research Reviews, Bind 38, Nr. 2, 03.2018, s. 602-624.

Publikation: Bidrag til tidsskriftReviewForskningpeer review

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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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