Angiotensin-converting enzyme inhibitors. New orally active antihypertensive (mercaptoalkanoyl)- and [(acylthio)alkanoyl]glycine derivatives.

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Suh JT, Skiles JW, Williams BE, Youssefyeh RD, Jones H, Loev B, Neiss ES, Schwab A, Mann WS, Khandwala A, et al.

Angiotensin-converting enzyme inhibitors. New orally active antihypertensive (mercaptoalkanoyl)- and [(acylthio)alkanoyl]glycine derivatives.

J Med Chem. 1985 Jan;28(1):57-66.

PubMed ID

2981324 [ View in PubMed

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Abstract

A variety of N-substituted (mercaptoalkanoyl)- and [(acylthio)alkanoyl]glycine derivatives was synthesized and their ability in inhibiting the activity of angiotensin-converting enzyme (ACE) was examined in vitro and in vivo. The acylthio derivatives prepared are assumed to act as prodrugs since they are much less active than the corresponding free SH compounds in vitro and can be expected to act in vivo only after conversion to the free sulfhydryl compounds. A number of these compounds are potent ACE inhibitors that lowered blood pressure in Na-deficient, conscious spontaneously hypertensive rats (SHR), a high renin model. One of the most active members of the series was (S)-N-cyclopentyl-N-[3-[(2,2-dimethyl-1-oxopropyl)thio]-2-methyl-1 -oxopropyl]glycine (REV 3659-(S), pivopril). Structure-activity relationships are discussed.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Captopril	Angiotensin-converting enzyme	IC 50 (nM)	23	N/A	N/A	Details
Captopril	Angiotensin-converting enzyme	IC 50 (nM)	27	N/A	N/A	Details
Captopril	Angiotensin-converting enzyme	IC 50 (nM)	17	N/A	N/A	Details
Enalapril	Angiotensin-converting enzyme	IC 50 (nM)	8000	N/A	N/A	Details