History of the Design of Captopril and Related Inhibitors of Angiotensin Converting Enzyme

  title={History of the Design of Captopril and Related Inhibitors of Angiotensin Converting Enzyme},
  author={David W. Cushman and Miguel A. Ondetti},
In describing the development of captopril and related antihypertensive drugs, we hope to resurrect a more specific meaning for the term "drug design," namely, the logical process whereby molecules are constructed for precise fit with a macromolecular receptor. Thus defined, drug design requires direct or indirect knowledge of the nature of the receptor, which in this case is the active center of a peptidase known historically as angiotensin converting enzyme (ACE). We believe that the… 
Angiotensin-converting enzyme inhibitors.
Toxin to medicine and bioisosterism in drug development: a study of the discovery and development of ACE inhibitors from snake venom
An account of the discovery, design and development of ACE inhibitors from an academic perspective and possibly, as a guide to future research is presented.
Potential antithrombotic and fibrinolytic properties of the angiotensin converting enzyme inhibitors
The totality of available clinical and experimental findings support the possibility of a direct linkage between the ACE system and vascular thrombosis that merits further prospective evaluation.
Use of Angiotensin‐Converting Enzyme Inhibitors as Monotherapy and in Combination with Diuretics and Calcium Channel Blockers
This paper provides guidance for selection of ACE inhibitors by examining the pharmacokinetics, pharmacodynamics, drug interactions, adverse effects, and cost of these agents.
Angiotensin-converting enzyme inhibitors in hypertension. A dozen years of experience.
The 12 years of clinical experience during which ACE inhibitors have become recognized as first-line agents for treating hypertension are reviewed, with beneficial effects on glucose handling, left-ventricular mass, quality of life, renal function, and myocardial protection becoming recognized.
Adverse Effects of the Angiotensin-Converting Enzyme Inhibitors
Attention to the principles of risk assessment, risk minimization, and patient monitoring are important when ACE inhibitor therapy is used for any indication, Provided these steps are taken, ACE inhibitors are generally a safe and effective class of drugs.
Food protein-derived renin-inhibitory peptides: in vitro and in vivo properties.
  • R. Aluko
  • Biology, Medicine
    Journal of food biochemistry
  • 2019
A summary of recent developments in the advances and efficacy testing of renin-inhibitory peptides is provided, which could offer a drug-free treatment for hypertension.
A Review of QSAR Studies to Predict Activity of ACE Peptide Inhibitors
Developed models were reviewed according to the applied dataset, descriptors, feature selection methods, model development and validation methods, and the selected descriptors for different datasets and models were compared and discussedaccording to the experimental findings.
Il sistema renina-angiotensina-aldosterone, l'enzima di conversione dell'angiotensina I e gli ACE-inibitori. Prospettiva storica e recenti acquisizioni
The evolution of the achievements about the angiotensin I converting enzyme is reviewed, the currently investigated relationship between RAAS and hemostatic system is assessed, and the rationale of ACE-inhibitors therapy in the treatment of arterial hypertension, acute myocardial infarction, heart failure, and diabetic nephropathy is evaluated.


Rational Design and Biochemical Utility of Specific Inhibitors of Angiotensin‐Converting Enzyme
The availability of structurally diverse ACE inhibitors with great potency and specificity provides a powerful biochemical tool for purification, localization, and characterization of ACE in different tissues, and for distinguishing related zinc metallopeptidases with similar properties.
Design of specific inhibitors of angiotensin-converting enzyme: new class of orally active antihypertensive agents.
A hypothetical model of the active site of angiotensin-converting enzyme, based on known chemical and kinetic properties of the enzyme, has enabled a new class of potent and specific inhibitors, carboxyalkanoyl and mercaptoalkanoysl derivatives of proline, to be designed.
Treatment of patients with severe hypertension by inhibition of angiotensin-converting enzyme.
It was found that haemodialysis or diuresis with frusemide enhanced the blood pressure response to the compound, and the presence of a measured low total blood volume was found to be associated with an exaggerated fall in blood pressure to a small dose of compound.
Angiotensin-converting enzyme inhibitors: biochemical properties and biological actions.
The chemistry and biochemistry of angiotensin-converting enzyme inhibitors are reviewed with emphasis on data published since the publication of previous reviews, to give the reader an appreciation of the medical implications of this new type of antihypertensive agent.
Conversion of Angiotensin I to Angiotensin II by Cell-free Extracts of Dog Lung
This communication describes some of the enzymes in extracts of dog lung that metabolize angiotensins I and II and particularly those catalysing the conversion ofAngiotensin I to angiotENSin II (“converting enzyme”) and the enzyme(s) responsible for the inactivation of ang Elliotensin II and angiotsin I are referred to as “destroying enzyme’.
[Renin-angiotensin system].
  • F. Suzuki
  • Biology
    Nihon rinsho. Japanese journal of clinical medicine
  • 1992
Investigations for the three-dimensional structure of human and mouse renins showed that the active site cleft had a less open arrangement in renins than that in other aspartic proteinases, although the general topology of both renins were quite similar.
An angiotensin converting-enzyme inhibitor to identify and treat vasoconstrictor and volume factors in hypertensive patients.
Abstract The antihypertensive action of nonapeptide competitive inhibitor of angiotensin-1-converting enzyme was evaluated in 13 hypertensive patients. In 12 a single injection (1 to 4 mg per kilog...
Rational design and biochemical utility of specific inhibitors of angiotensinconverting enzyme
  • Cardiovasc Pharmacol
  • 1987