Smithkline Beckman Corporation

Smithkline Beecham Corporation

Smithkline Corporation

Fadia E Ali

William F Huffman

James Martin Samanen

William Henry Miller

William Edward Bondinell

Richard McCulloch Keenan

Thomas Wen-Fu Ku

Michael L Moore

Kenneth M Snader

Garland R Marshall

Joseph W Venslavsky

Chet Kwon

Thomas The Nguyen

Tobias Oregon Yellin

M Amparo Lago

Raul Rolando Calvo

Robert D Krell

Dennis T Takata

Vitronectin receptor antagonists

This invention relates to compounds of the formula: ##STR1## which are effective for inhibiting platelet aggregation, pharmaceutical compositions for effecting such activity, and a method for inhibiting platelet aggregation.

Fibrinogen receptor antagonists

Benzimidazoles/Imidazoles Linked to a Fibrinogen Receptor Antagonist

This invention relates to compounds which are effective for inhibiting platelet aggregation, pharmaceutical compositions for effecting such activity, a method for inhibiting platelet aggregation and clot formation in a mammal, and a method for inhibiting reocclusion of a blood vessel following fibrinolytic therapy.

Anti-aggregatory peptides

This invention relates to compounds of the formula: ##STR1## wherein: A' is absent, Asn, Gln, Ala or Abu;

Cyclic anti-aggregatory peptides

Vasopressin antagonists which have a dipeptide tail composed of a neutral and basic amino acid unit demonstrate potent V.sub.1 and V.sub.2 -antagonist activity. Two species of this invention, which are prepared by solid phase peptide synthesis, are [1-(.beta.-mercapto-.beta.,.beta.-cyclopentamethylene propionic acid)-2-(O-ethyl)-D-tyrosine-4-valine-7-tyrosine-8-arginine-9-desglycine]- vasopressin and [1-(.beta.-mercapto-.beta.,.beta.-cyclopentamethylenepropionic acid)-2-(O-ethyl)-D-tyrosine-4-valine-7-arginine-8-tyrosine-9-desglycine]- vasopressin.

Tyr-Arg-vasopressin antagonists

Vasopressin antagonists which have a tripeptide side chain comprised of three basic amino acids, such as arginine, lysine or ornithine, demonstrate potent V.sub.1 and V.sub.2 -antagonist activity. A species of the invention, which is prepared by conventional peptide sequencing, is [1-(.beta.-mercapto-.beta.,.beta.-cyclopentamethylenepropionic acid)-2-(O-ethyl)-D-tyrosine-4-valine-7-arginine-8-arginine-9-arginine]-va sopression.

Arg-arg-arg-vasopressin antagonists

Vasopressin antagonists which have a dipeptide side chain comprised of two basic amino acids demonstrate potent V.sub.1 and V.sub.2 -antagonist activity. A species of the invention, which is prepared by conventional peptide sequencing, is [1-(.beta.-mercapto-.beta.,.beta.-cyclopentamethylene propionic acid)-2-(O-ethyl)-D-tyrosine-4-valine-7-arginine-8-arginine-9-desglycine]- vasopressin.

ARG.sup.7 -ARG.sup.8 -vasopressin antagonists

Peptides having vasopressin antagonist activity are prepared by a peptide synthesizer to insert a N-methylarginine at the 7-position of the structure. An example of this series of compounds is [1-(.beta.-mercapto-.beta.,.beta.-cyclopentamethylenepropionic acid)-2-(O-ethyl-D-tyrosine)-4-valine-7-desproline-8-N-methylarginine-9-de sglycine]-vasopressin.

Des-proline-N-methylarginine vasopressins

Vasopressin derivatives having V.sub.1 and oxytocin antagonist activity whose structures are characterized by a Mpa unit at position 1 and a des-Pro unit at position 7 are prepared by standard peptide synthetic methods also using an oxidative cyclization of a dimercaptan. Representative species are [1-deaminopenicillamine-2-(O-methyl)-tyrosine-7-desproline-8-arginine-9-de sglycine]vasopressin or [1-.beta.-mercaptopropionic acid-2-D-(O-ethyl)tyrosine-3-isoleucine-4-threonine-7-desproline-8-arginin e-9-desglycine]-vasopressin.

Compositions and methods for producing vasodilation and antioxytocic

V1-vasopressin antagonists

Certain octapeptides, which have structures characterized by being a six unit cyclic peptide ring with a dipeptide tail with no proline unit, have vasopressin antagonist activity. An important species of the group is [1-(.beta.-mercapto-.beta.,.beta.-cyclopentamethylenepropionic acid)-2-(O-ethyl-D-tyrosine)-4-valine]-7-desproline-8-arginine-vasopressin .

Des-proline vasopressin antagonists

Certain heptapeptides which have structures characterized by being a six unit cyclic peptide ring with an arginine or lysine tail have vasopressin antagonist activity. An important species of the group is [1-(.beta.-mercapto-.beta.,.beta.-cyclopentamethylenepropionic acid)-2-(O-ethyl-D-tyrosine)-4-valine-7-desproline-8-arginine-9-desglycine ]-vasopressin.

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Cherry Hill, NJ, United States of America

Fadia E Ali