G.d. Searle & Company

Robert H Mazur

James M Schlatter

Donald W Hansen, Jr

David A Jones, Jr

Daniel R Pilipauskas

Arthur H Goldkamp

John S Baran

E Ann Hallinan

Alan E Moorman

Richard A Mikulec

Judith A Reuter

Tom Lindberg

Doug Steinman

David A Tyner

Eleanor A Hallinan

A series of ethers and thioethers of 5-methanol thiohydantoins, unsubstituted at the number one position heterocyclic nitrogen atom of the thiohydantoin ring, useful in reversing the effects of collagen and ADP-induced platelet aggregation.

Thiohydantoin inhibitors of collagen-induced and ADP-induced platelet

The invention relates to novel substituted tyrosyl alanine dipeptide amides of the formula: ##STR1## and the pharmaceutically acceptable acid addition salts thereof wherein R.sub.1 represents straight or branched lower alkyl having 1 to 4 carbons;

Substituted tyrosyl alanine dipeptide amides

The invention relates to tetrapeptides of the formula I: ##STR1## which are useful as renin inhibition/antihypertensive agents.

Tetrapeptide amides in the treatment of hypertension

The invention relates to novel enkephalin analogs of the formula: ##STR1## which are useful as analgesic agents.

Enkephalin analogs

The invention discloses cyclohexyl and phenyl substituted enkephalin derivatives of the formula: ##STR1## Where R.sub.1, R.sub.2, R.sub.4, and R.sub.8 is hydrogen or alkyl of R.sub.3 is alkylthioalkyl or alkylsulfinylalkyl, X is: ##STR2## R.sub.5 is cyclohexylmethyl, phenylmethyl, optionally substituted by --NO.sub.2, R.sub.6 is cyclohexyl or phenyl optionally substituted by R.sub.7 and R.sub.7 is hydrogen, an alkyl ester of carboxylic acid or hydroxyalkyl and the pharmaceutically acceptable salts, which are useful as analgesic agents.

Cyclohexyl and phenyl substituted enkephalins

N-Adamantane-substituted tetrapeptide amides and the pharmacologically acceptable salts thereof are disclosed herein. These compounds are analogs of enkephalin wherein the methionine or leucine of position 5 has been substituted by an adamantyl amide and the glycine of position 2 has been substituted by various amino acid residues. Optionally the tyrosine of position 1 and the phenylalanine of position 4 may be substituted by various amino acid residues. These compounds exhibit agonist activity at opiate receptor sites and are useful as analgesics.

N-Adamantane-substituted tetrapeptide amides

The sarcosine.sup.1 dehydroalanine.sup.8 angiotensin II derivatives of the present invention are potent angiotensin blockers.

Sarcosine.sup.1 dehydroalanine.sup.8 angiotensin II derivatives

Analogs of enkephalin having agonist activity at opiate receptors are disclosed herein. These analogs are useful as analgesics, non-addicting narcotic antagonists and anti-diarrheal agents.

2 AND 3-SUBSTITUTED ENKEPHALINS

3-Amino-N-substituted succinamic acids, prepared by coupling of a protected L-aspartic acid derivative with the appropriate amine followed by cleavage of the protecting groups, are potent sweetening agents and also exhibit pharmacological, e.g. anti-inflammatory, properties.

3-Amino-N-substituted succinamic acids

This invention encompasses novel tetrapeptide amides and their intermediates containing an L-aspartic acid residue. These peptides are inhibitors of gastric acid secretion and therefore useful in the treatment of ulcers.

Anti-ulcer polypeptides containing L-aspartic acid and intermediates

The above-captioned compounds, prepared by coupling of a protected L-aspartic acid derivative with the appropriate amine followed by cleavage of the protecting groups, are potent sweetening agents and exhibit also pharmacological, e.g. anti-inflammatory, properties.

3-Amino-N-substituted succinamic acids and intermediates thereto

Octapeptide derivatives characterized by an oxygen or sulfur-containing moiety in the C-terminal position are potent inhibitors of the pharmacological effects of Angiotensin and possess the additional advantage of a favorable antagonist/agonist ratio.

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Chicago, IL, United States of America

Robert H Mazur