Smith, Robert J;
Perez-Ternero, Cristina;
Conole, Daniel;
Martin, Capucine;
Myers, Samuel H;
Hobbs, Adrian J;
Selwood, David L;
(2022)
A Series of Substituted Bis-Aminotriazines Are Activators of the Natriuretic Peptide Receptor C.
Journal of Medicinal Chemistry
, 65
(7)
pp. 5495-5513.
10.1021/acs.jmedchem.1c01974.
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Abstract
C-type natriuretic peptide (CNP) is involved in the regulation of vascular homeostasis, which is at least partly mediated through agonism of natriuretic peptide receptor C (NPR-C), and loss of this signaling has been associated with vascular dysfunction. As such, NPR-C is a novel therapeutic target to treat cardiovascular diseases. A series of novel small molecules have been designed and synthesized, and their structure-activity relationships were evaluated by a surface plasmon resonance binding assay. The biological activity of hit compounds was confirmed through organ bath assays measuring vascular relaxation and inhibition of cAMP production, which was shown to be linked to its NPR-C activity. Lead compound 1 was identified as a potent agonist (EC50 ∼ 1 μM) with promising in vivo pharmacokinetic properties.
| Type: | Article |
|---|---|
| Title: | A Series of Substituted Bis-Aminotriazines Are Activators of the Natriuretic Peptide Receptor C |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1021/acs.jmedchem.1c01974 |
| Publisher version: | https://doi.org/10.1021/acs.jmedchem.1c01974 |
| Language: | English |
| Additional information: | This is an Open Access article published under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) Licence (https://creativecommons.org/licenses/by-nc-nd/4.0/). |
| UCL classification: | UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Wolfson Inst for Biomedical Research UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10146372 |
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