Iwaki Takehiko, Oyama Yoshiaki, Tomoo Toshiyuki, Tanaka Taisaku, Okamura Yoshihiko, Sugiyama Masako, Yamaki Akira, Furuya Mayumi
Asubio Pharma Co., Ltd, 6-4-3, Minatojima-Minamimachi, Chuo-ku, Kobe 650-0047, Japan.
Asubio Pharma Co., Ltd, 6-4-3, Minatojima-Minamimachi, Chuo-ku, Kobe 650-0047, Japan.
Bioorg Med Chem. 2017 Mar 15;25(6):1762-1769. doi: 10.1016/j.bmc.2017.01.026. Epub 2017 Jan 28.
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.
通过对三嗪衍生物进行随机筛选及后续结构修饰，获得了利钠肽受体A（NPR-A）的新型激动剂。提高体外活性的关键结构特征是三嗪单体衍生物的二聚化。非肽衍生物7c和13a在体外显示出高效的NPR-A激动活性，在体内显示出利尿活性。这些结果表明，非肽类小分子为充血性心力衰竭的新疗法开辟了可能性。
