Syntheses and Biological Activities of Renin Inhibitors Containign Statine Analogues

Takahide NISHI; Fujio SAITO; Hitoshi NAGAHORI; Mitsuru KATAOKA; Yasuhiro MORISAWA; Yuichiro YABE; Mitsuya SAKURAI; Susmu HIGASHIDA; Machiko SHOJI; Yoichi MATSUSHITA; Yasuteru IIJIMA; Kiyoshi OHIZUMI; Hiroyuki KOIKE

doi:10.1248/cpb.38.103

西剛秀, 斉藤冨士夫, 永堀均, 片岡満, 森沢靖弘, 矢部裕一郎, 桜井満也, 東田勧, 庄子真知子, 松下洋一, 飯島康輝, 大泉喜代志, 小池博之

著者情報

キーワード: renin inhibitor, ES 6864, oral administration, 2(R)-substituted-3-aminocarbonylpropionic acid, statine analogue

ジャーナルフリー

1990 年 38 巻 1 号 p. 103-109

DOI https://doi.org/10.1248/cpb.38.103

詳細

抄録

Syntheses and biological activities of dipeptide renin inhibitors that contain statine analogues are described. The key steps fo the synthetic approach to dipeptide renin inhibitors are the asymmetric synthesls of 2(R)-substituted-3-aminocarbonylpropionic acids and the diastereoselective syntheses of (3S, 4S)-statine analogues. These inhibitors (2, 14-40) inhibited human renin in the 3-140 nM range. Inhibitor ES 6864 (2) was found to be a highly potent inhibitor of human renin (IC₅₀ : 4.6×10^-9M) and showed high enzyme specificity. Oral administration of ES 6864 at 3 mg/kg to conscious, sodium-depleted marmosets inhibted plasma renin activity (PRA) more than 80% after 1h.

責任著者(Corresponding author)

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