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

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 (EC 50 ∼ 1 μM) with promising in vivo pharmacokinetic properties.

One‐Pot Multicomponent Synthesis of Bis(diamino‐1,3,5‐triazines) under Microwave Irradiation

“…[24] CRO15 demonstrated a potent anticancer effect in vitro and in vivo, and this effect is associated with the activation of the AMPK pathway and inhibition of MELK kinase. Recently, bis-triazine 1 was reported [25] as a potent agonist of natriuretic peptide receptor C.…”