Discovery and dimeric approach of novel Natriuretic Peptide Receptor A (NPR-A) agonists

被引：9
|
作者：
Iwaki, Takehiko [1 ]
Oyama, Yoshiaki [1 ]
Tomoo, Toshiyuki [1 ]
Tanaka, Taisaku [1 ]
Okamura, Yoshihiko [1 ]
Sugiyama, Masako [1 ]
Yamaki, Akira [1 ]
Furuya, Mayumi [1 ]
机构：
[1] Asubio Pharma Co Ltd, Chuo Ku, 6-4-3 Minatojima Minamimachi, Kobe, Hyogo 6500047, Japan
来源：
BIOORGANIC & MEDICINAL CHEMISTRY | 2017年 / 25卷 / 06期
关键词：
Natriuretic Peptide Receptor A; Agonist; Triazine derivatives; Congestive heart failure;
D O I：
10.1016/j.bmc.2017.01.026
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
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. (C) 2017 Elsevier Ltd. All rights reserved.
引用
收藏
页码：1762 / 1769
页数：8
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