Merck + Co., Inc.

Stephen F Brady

Daniel F Veber

Ruth F Nutt

Joseph P Vacca

William C Lumma, Jr

Thomas Joseph Tucker

Victor M Garsky

Dong-Mei Feng

Jules A Shafer

Philip E Sanderson

Terry A Lyle

Mark E Duggan

Roger M Freidinger

Yueming Li

James E Bruce

Kenneth J Stauffer

Mohinder Sardana

Elizabeth Chen-Dodson

Xiaoting Tang

Mark G Bock

Theresa M Williams

Craig Alan Coburn

Joshua S Boger

Terrence M Ciccarone

Sandor L Varga

Ming-Tain Lai

Joseph M Pawluczyk

Harvey Schwam

Carl H Hoffman

S Dale Lewis

Martin Hichens

Keith M Witherup

Ming-Chih Crouthamel

Mary A Napier

Richard L Vandlen

Willie L Whitter

The present invention provides synthetic &#x3b2;-secretase peptide substrates useful in various assays for measuring &#x3b2;-secretase activity. Antibodies that recognize the synthetic substrates and uses of the antibodies in various assays are disclosed. The herein disclosed peptide substrates are hydrolyzed at rates substantially faster than the attendant Swedish mutant APP from which the substrate sequences are derived.

Beta-secretase substrates and uses thereof

The present invention provides compounds that are inhibitors of the proteolytic activity of the enzyme &#x3b2;-secretase, pharmaceutically acceptable salts of the compounds, pharmaceutical compositions comprising the compounds, processes for making the compounds, and methods of using the compounds to treat Alzheimers disease.

&#x3b2;-secretase inhibitors

Chemical conjugates which comprise oligopeptides, having amino acid sequences that are selectively proteolytically cleaved by free prostate specific antigen (PSA) and known cytotoxic agents are disclosed. The conjugates of the invention are characterized by attachment of the cleavable oligopeptide to the oxygen atom at the 4-position on a vinca drug that has be desacetylated. Such conjugates are useful in the treatment of prostatic cancer and benign prostatic hypertrophy (BPH).

Conjugates useful in the treatment of prostate cancer

Chemical conjugates which comprise oligopeptides, having amino acid sequences that are selectively proteolytically cleaved by free prostate specific antigen (PSA) and known cytotoxic agents are disclosed. The conjugates of the invention are characterized by a diamine linker between the oligopeptide and vinblastine. Such conjugates are useful in the treatment of prostatic cancer and benign prostatic hypertrophy (BPH).

A compound which inhibits human thrombin and where has the structure ##STR1## such as ##STR2##

Thrombin inhibitors

Compounds of the invention are useful in inhibiting thrombin and associated thrombotic occlusions and have the following structure: ##STR1## for example: ##STR2##

Pyridinone thrombin inhibitors

Piperidine and hexahydropyridazine thrombin inhibitors

4-substituted cyclohexylamine derivatives which are thrombin catalytic site inhibitors and which are useful as anticoagulants. These compounds show selectivity for thrombin over other trypsin-like enzymes and have oral bioavailability. They have the formula ##STR1## for example ##STR2##

Compounds of the invention have the following structure: ##STR1## for example ##STR2## These compounds inhibit thrombin and associated thrombosis.

Pyrrolidine thrombin inhibitors

A fibrinogen receptor antagonist of the formula

Fibrinogen receptor antagonists

A fibrinogen receptor antagonist of the formula ##STR1## wherein XX represents a synthetic alpha-amino acid containing a linear side chain and ZZ represents a sequence of 1, 2, 3 or 4 amino acids.

Atrial natriuretic factor analogs containing N-alkylated amino acids and showing enhanced potency and increased metabolic stability. These analogs have natriuretic, diuretic and vasorelaxant activity, making them suitable for treating congestive heart failure and renal hypertension.

Peptides having atrial natriuretic factor activity

Analogs of the 17-membered ring portion of ANF wherein the cysteine moiety is replaced with dipeptidyl moieties, specifically, Phe-Pro, NMP-Pro, Pro-Pro, Val-Pro, Lys-Pro, Ile-Pro, Arg-Pro, HAr-Pro, Dly-Pro, Arg-Pro, Lys-BAr, Arg-Pro, CyA-CyA, Cys-Cys, or with .alpha.-aminoheptanoic acid result in analogs of ANF having increased potencies and metabolic stability.

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Philadelphia, PA, United States of America

Stephen F Brady