title: Syntheses and biological activities of renin inhibitors containing statine analogues.
abstract: Syntheses and biological activities of dipeptide renin inhibitors that contain statine analogues are described. The key steps of the synthetic approach to dipeptide renin inhibitors are the asymmetric synthesis 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 x 10(-9) M) and showed high enzyme specificity. Oral administration of ES 6864 at 3 mg/kg to conscious, sodium-depleted marmosets inhibited plasma renin activity (PRA) more than 80% after 1 h.
authors.affiliation: Medicinal Chemistry Research, Sankyo Co., Ltd., Tokyo, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Nishi
authors.forename: F
authors.initials: F
authors.lastname: Saito
authors.forename: H
authors.initials: H
authors.lastname: Nagahori
authors.forename: M
authors.initials: M
authors.lastname: Kataoka
authors.forename: Y
authors.initials: Y
authors.lastname: Morisawa
authors.forename: Y
authors.initials: Y
authors.lastname: Yabe
authors.forename: M
authors.initials: M
authors.lastname: Sakurai
authors.forename: S
authors.initials: S
authors.lastname: Higashida
authors.forename: M
authors.initials: M
authors.lastname: Shoji
authors.forename: Y
authors.initials: Y
authors.lastname: Matsushita
mesh_terms: D000596:Amino Acids / Q000138:chemical synthesis / Q000494:pharmacology*; D000818:Animals; D002143:Callitrichinae; D055598:Chemical Phenomena; D002621:Chemistry; D008297:Male; D012083:Renin / Q000097:blood; D013329:Structure-Activity Relationship; D000092502:Renin Inhibitors
chemical_list: D000596:Amino Acids; D012083:Renin; D000092502:Renin Inhibitors; C013165:statine