Discovery and Dimeric Approach of Novel Natriuretic Peptide Receptor A (NPR-A) Agonists

Publication date: Available online 28 January 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Takehiko Iwaki, Yoshiaki Oyama, Toshiyuki Tomoo, Taisaku Tanaka, Yoshihiko Okamura, Masako Sugiyama, Akira Yamaki, Mayumi Furuya
Novel agonists of the Natriuretic Peptide Receptor A (NPR-A) were obtained through random screening and subsequent structural modification of triazine derivatives. The key structural feature to improve in vitro activity was the dimerization of triazine monomer derivatives. The non peptide derivative 7c and 13a showed highly potent NPR-A agonistic activity in vitro and diuretic activity in vivo. These results implied that non-peptidic small molecules open the possibility of new therapy for congestive heart failure.

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