Slade J, Stanton J L, Ben-David D, Mazzenga G C
J Med Chem. 1985 Oct;28(10):1517-21. doi: 10.1021/jm00148a024.
The synthesis of chiral 1,5-benzothiazepines 2a-c, 14a-c, 15c, and 16a prepared from cysteine is described. In vitro inhibition of angiotensin converting enzyme (ACE) is reported for each compound. Compound 2c was the most potent in vitro having an IC50 of 2.95 nM. The ester of 2c, i.e. 14c, was found to inhibit the AI pressor response by 75% at a dose of 0.05 mg/kg iv and by 39% at 1.0 mg/kg po. Additionally, 14c lowered blood pressure in the spontaneous hypertensive rat (SHR) by 35 mmHg, at a dose of 10 mg/kg po.
描述了由半胱氨酸制备手性1,5 - 苯并硫氮杂䓬2a - c、14a - c、15c和16a的合成方法。报道了每种化合物对血管紧张素转换酶（ACE）的体外抑制作用。化合物2c在体外活性最强，IC50为2.95 nM。发现2c的酯即14c，静脉注射剂量为0.05 mg/kg时可抑制血管紧张素I升压反应75%，口服剂量为1.0 mg/kg时可抑制39%。此外，口服剂量为10 mg/kg时，14c可使自发性高血压大鼠（SHR）的血压降低35 mmHg。
