A Series of Substituted Bis-Aminotriazines Are Activators of the Natriuretic Peptide Receptor C.
J Med Chem
; 65(7): 5495-5513, 2022 04 14.
Article
in En
| MEDLINE
| ID: mdl-35333039
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 â¼ 1 µM) with promising in vivo pharmacokinetic properties.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Signal Transduction
/
Natriuretic Peptide, C-Type
Language:
En
Journal:
J Med Chem
Journal subject:
QUIMICA
Year:
2022
Document type:
Article
Affiliation country:
United kingdom