A NEW POTENT INHIBITOR OF CONVERTING ENZYME: (2R, 4R)-2-(2-HYDROXYPHENYL)-3-(3-MERCAPTOPROPIONYL)-4-THIAZOLIDINECARBOXYLIC ACID(SA446)

概要

論文の詳細を見る
(2R, 4R)-2-(2-Hydroxyphenyl)-3-(3-mercaptopropionyl)-4-thiazolidinecarboxylic acid (SA446) is a novel potent converting enzyme inhibitor having a sulfhydryl group in the molecule. SA446 inhibited the activity of semi-purified rabbit lung converting enzyme (1C50=6 nM). The contractile response of isolated guinea pig ileum to angiotensin I (Al) was markedly inhibited by SA446 (IC50=28 nM). On the other hand, SA446 augmented the contraction to bradykinin (BK) (AC50=0.7 nM), but did not affect the contraction caused by angiotensin II (AII), acetylcholine and histamine. These <I>in vitro</I> potencies of SA446 were 4 to 5 times larger than those of captopril. SA446 inhibited the pressor response to Al in rats (ID50=0.06 mg/kg, i.v., 0.48 mg/kg, p.o.) and dogs (ID50=0.01 mg/kg, i.v.). SA446 augmented the depressor response to BK (AD50=0.009 mg/ kg, i.v.), but did not affect the pressor responses to All and norepinephrine in rats. These <I>in vivo</I> activities of SA446 in dogs were more potent than those of captopril, but the reverse was seen in rats. Oral administration of SA446 had a hypotensive effect on two-kidney, one-clip renal hypertensive rats and spontaneously hypertensive rats, at doses over 3 and 10 mg/kg, respectively. However, the blood pressure of normotensive and DOCA-salt hypertensive rats was not affected by SA446, in doses up to 100 mg/kg. These results indicate that oral SA446 is a potent active inhibitor of converting enzyme and may be classed as an antihypertensive agent.
社団法人日本薬理学会の論文

A NEW POTENT INHIBITOR OF CONVERTING ENZYME: (2R, 4R)-2-(2-HYDROXYPHENYL)-3-(3-MERCAPTOPROPIONYL)-4-THIAZOLIDINECARBOXYLIC ACID(SA446)

スポンサーリンク

概要

著者

関連論文

スポンサーリンク