title: Discovery and dimeric approach of novel Natriuretic Peptide Receptor A (NPR-A) agonists.
abstract: 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.
authors.affiliation: Asubio Pharma Co., Ltd, 6-4-3, Minatojima-Minamimachi, Chuo-ku, Kobe 650-0047, Japan. Electronic address: iwaki.takehiko.v7@asubio.co.jp.
authors.forename: Takehiko
authors.initials: T
authors.lastname: Iwaki
authors.affiliation: Asubio Pharma Co., Ltd, 6-4-3, Minatojima-Minamimachi, Chuo-ku, Kobe 650-0047, Japan.
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Oyama
authors.affiliation: Asubio Pharma Co., Ltd, 6-4-3, Minatojima-Minamimachi, Chuo-ku, Kobe 650-0047, Japan.
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Tomoo
authors.affiliation: Asubio Pharma Co., Ltd, 6-4-3, Minatojima-Minamimachi, Chuo-ku, Kobe 650-0047, Japan.
authors.forename: Taisaku
authors.initials: T
authors.lastname: Tanaka
authors.affiliation: Asubio Pharma Co., Ltd, 6-4-3, Minatojima-Minamimachi, Chuo-ku, Kobe 650-0047, Japan.
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Okamura
authors.affiliation: Asubio Pharma Co., Ltd, 6-4-3, Minatojima-Minamimachi, Chuo-ku, Kobe 650-0047, Japan.
authors.forename: Masako
authors.initials: M
authors.lastname: Sugiyama
authors.affiliation: Asubio Pharma Co., Ltd, 6-4-3, Minatojima-Minamimachi, Chuo-ku, Kobe 650-0047, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Yamaki
authors.affiliation: Asubio Pharma Co., Ltd, 6-4-3, Minatojima-Minamimachi, Chuo-ku, Kobe 650-0047, Japan.
authors.forename: Mayumi
authors.initials: M
authors.lastname: Furuya
mesh_terms: D000818:Animals; D018360:Crystallography, X-Ray; D006152:Cyclic GMP / Q000378:metabolism; D019281:Dimerization; D004232:Diuretics / Q000494:pharmacology; D055808:Drug Discovery; D006801:Humans; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D008297:Male; D013058:Mass Spectrometry / Q000379:methods; D015394:Molecular Structure; D066244:Proton Magnetic Resonance Spectroscopy; D051381:Rats; D017207:Rats, Sprague-Dawley; D017461:Receptors, Atrial Natriuretic Factor / Q000819:agonists*; D013329:Structure-Activity Relationship; D014227:Triazines / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D004232:Diuretics; D014227:Triazines; D017461:Receptors, Atrial Natriuretic Factor; C091715:atrial natriuretic factor receptor A; D006152:Cyclic GMP
keywords: Agonist; Congestive heart failure; Natriuretic Peptide Receptor A; Triazine derivatives