(R)-3-((S)-1-carboxy-5-(4-piperidyl)pentyl)amino-4-oxo-2,3,4,5-tetrahydro-1,5-benzothiazepine-5-acetic acid (CV-5975): A new potent and long-lasting inhibitor of angiotensin converting enzyme.

Inhibition of Angiotensin Converting Enzyme by (R)-3-[(S)-1-Carboxy-5-(4-Piperidyl)pentyl]amino-4-Oxo-2,3,4,5-Tetrahydro-1,5-Benzothiazepine-5-Acetic Acid (CV-5975), a Non-Sulfhydryl Compound

“…Thus, there are differences in the BK-inactivation of CV-5975 between in vitro and in vivo conditions. Difference in BK-inactivation was observed between delapril and captopril, in vitro and in vivo (9). Here, the ratio of the potencies between delapril and captopril was about 250 times, in vitro.…”

“…These obser vations mean that CV-5975 inhibits more sensitively the inactivation of BK than it does the conversion of A-I to A-ll. We reported that delapril, another ACE inhibitor, inhibits more sensitively the conversion of A-I to A-II than it did the inactivation of BK (9). One explanation for this dissociation of A-1 conversion and BK-inactivation among the ACE inhibitors may relate to differences in the kinetic characteristics of ACE, depending on the substrates, and the difference in multiple binding properties of inhibitors to ACE (19).…”

“…We found that (R)-3-[(S)-1-carboxy-5-(4 piperidyl)pentyl]amino-4-oxo-2,3,4,5-tetra hydro-1,5-benzothiazepine-5-acetic acid, CV-5975 ( Fig. 1), seemed to be the most promising ACE inhibitor (9). This agent has a potent and long lasting antihypertensive activity, as noted in various models of hyper tension in laboratory animals (10).…”

“…Captopril and enalapril are also effective in treating congestive heart failure (5). We reported the design and structure-activity relationships of (R)-3-amino-4-oxo-2,3,4,5 tetrahydro-1,5-benzothiazepine-5-acetic acid derivatives for ACE inhibitory activity (6)(7)(8)(9). We found that (R)-3-[(S)-1-carboxy-5-(4 piperidyl)pentyl]amino-4-oxo-2,3,4,5-tetra hydro-1,5-benzothiazepine-5-acetic acid, CV-5975 ( Fig.…”

Catalytic Enantioselective Synthesis of Protecting‐Group‐Free 1,5‐Benzothiazepines

“…Depicted in Scheme1 are representative examples includingt he antidepressanta gent (R)-(À)-thiazesim marketed as its hydrochloride salt Altinil, [2] diltiazeme mployed for the treatment of antihypertension and angina, [3] and the ACE inhibitor CV-5975 . [4] Unsurprisingly,avariety of protocols have been developed for the racemic synthesis of these compounds, [5] whicha re also endowedw ith antimicrobial, antifungal, anti-HIV,a nticancer, and antiulcer activities. [1] Concerning their asymmetric synthesis, al imited number of procedures relies on racemic resolution [2a, 6] and occasional examplesh ave been reported in methodological studies.…”