A hypothetical model of the active site of angiotensin-converting enzyme, based on known chemical and kinetic properties of the enzyme, has enabled us to design a new class of potent and specific inhibitors. These compounds, carboxyalkanoyl and mercaptoalkanoyl derivatives of proline, inhibit the contractile response of guinea pig ileal strip to angiotensin I and augment its response to bradykinin. When administered orally to rats, these agents inhibit the pressor effect of angiotensin I, augment the vasodepressor effect of bradykinin, and lower blood pressure in a model of renovascular hypertension.

https://science.sciencemag.org/content/sci/196/4288/441.full.pdf

Design of specific inhibitors of angiotensin-converting enzyme: new class of orally active antihypertensive agents

https://digital.csic.es/bitstream/10261/63157/4/Gomez-Guillen-collagenreview_CSIC.pdf

Functional and bioactive properties of collagen and gelatin from alternative sources: A review

The influence of natural products upon drug discovery.

Renin-angiotensin system: biochemistry and mechanisms of action.

3-(Acylamino)-5-phenyl-2H-1,4-benzodiazepines, antagonists of the peptide hormone cholecystokinin (CCK), are described. Developed by reasoned modification of the known anxiolytic benzodiazepines, these compounds provide highly potent, orally effective ligands selective for peripheral (CCK-A) receptors, with binding affinities approaching or equaling that of the natural ligand CCK-8. The distinction between CCK-A receptors on the one hand and CNS (CCK-B), gastrin, and central benzodiazepine receptors on the other is demonstrated by using the structure-activity profiles of the new compounds. Details of the binding of these agents to CCK-A receptors are examined, and the method of development of these compounds is discussed in terms of its relevance to the general problem of drug discovery.

Methods for drug discovery: development of potent, selective, orally effective cholecystokinin antagonists

A method is provided for slowing the progression of atherosclerosis in coronary arteries in hypertensive or normotensive patients and reducing or eliminating atherosclerotic lesions in such patients in a mammalian species by administering an ACE inhibitor, especially one containing a mercapto moiety, such as captopril or zofenopril.

Method for stabilizing or causing regression of atherosclerosis in coronary arteries employing an ace inhibitor

Peptides having the formula ##STR1## wherein R 1 is hydrogen and R 2 is hydroxyl, alkyl, aryl, arylalkyl, alkoxy, alkylthio, aryloxy, arylthio, halogen or azido, or R 1 and R 2 are the same and each is hydrogen, halogen, alkoxy or alkylthio, or R 1 and R 2 together are oxo, --O--(CH 2 ) n --O--, or --S--(CH 2 ) n --S--, wherein n is 1 or 2; R 3 is hydrogen, alkyl or trifluoromethyl; R 4 is hydrogen or an acyl protecting group; and R 5 is hydrogen or alkyl; are inhibitors of angiotensin converting enzyme and can be used for the treatment of hypertension in mammals.

Tripeptide inhibitors of angiotensin-converting enzyme

New carboxyalkylacylamino acids which are derivatives of proline, pipecolic acid and azetidine-2-carboxylic acid and have the general formula ##STR1## are useful as angiotensin converting enzyme inhibitors.

Reduction of blood pressure with carboxyalkylacyl-pipecolic acid derivatives

Acylmercaptoalkanoyl compounds of the formula ##STR1## wherein n is an integer from one to fifteen possess enkephalinase inhibition activity and are useful as analgesic agents.

Certain [(lower alkanoyl-thio)methyl-1-oxo-3-phenyl propyl amino]benzene lower alkanoic acid or ester derivatives which inhibit enkephalinase

A stable composition of the sulfated octapeptide, ##EQU1## having cholecystokinin activity, is obtained by lyophilizing an aqueous solution of the octapeptide and NaCl.

Miguel A. Ondetti

Papers

Method for stabilizing or causing regression of atherosclerosis in coronary arteries employing an ace inhibitor

Tripeptide inhibitors of angiotensin-converting enzyme

Reduction of blood pressure with carboxyalkylacyl-pipecolic acid derivatives

Certain [(lower alkanoyl-thio)methyl-1-oxo-3-phenyl propyl amino]benzene lower alkanoic acid or ester derivatives which inhibit enkephalinase

Method of stabilizing an injectable composition of a cholecystokinin active octapeptide