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

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 lossof this signaling has been associated with vascular dysfunction. As such, NPR-C is a novel therapeutictarget to treat cardiovascular diseases. A series of novel small molecules have been designed andsynthesized, and their structure-activity relationships were evaluated by a surface plasmon resonancebinding assay. The biological activity of hit compounds was confirmed through organ bath assaysmeasuring vascular relaxation and inhibition of cAMP production, which was shown to be linked to its NPR-C activity. Lead compound1was identified as a potent agonist (EC50 similar to 1 mu M) with promising in vivo pharmacokinetic properties