A Series of Substituted Bis-Aminotriazines Are Activators of the Natriuretic Peptide Receptor C

Autor:	Robert J. Smith, Cristina Perez-Ternero, Daniel Conole, Capucine Martin, Samuel H. Myers, Adrian J. Hobbs, David L. Selwood
Rok vydání:	2022
Předmět:	Drug Discovery Homeostasis Molecular Medicine Natriuretic Peptide C-Type Signal Transduction
Zdroj:	Journal of Medicinal Chemistry. 65:5495-5513
ISSN:	1520-4804 0022-2623
DOI:	10.1021/acs.jmedchem.1c01974
Popis:	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
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::9ffab2223d28030fa379fcc2bcd93b0f https://doi.org/10.1021/acs.jmedchem.1c01974 Zobrazit plný text záznamu