Merck + Co., Inc.

Merck Sharp + Dohme Corp.

Methylgene, Inc.

Jeffrey Donald Hermes

Helen Y Chen

Seongkon Kim

Richard T Cummings

William H Parsons

Peter J Sinclair

Milton L Hammond

Arkadii Vaisburg

Alan D Adams

Timothy A Blizzard

John J Acton, Iii

Stephane Raeppel

Sookhee Nicole Ha

Kevin D Dykstra

Michael Mannion

Timothy Allen Blizzard

Jubrail Rahil

A Brian Jones

Nelo R Rivera

Katherine Young

Frederic Gaudette

Jason Eugene Imbriglio

Ian Mangion

David E Moller

Jane Yang Wu

Candido Gude

Michael Shevlin

Qiang Tan

Scott P Salowe

Gaochao Zhou

Nafsika Georgopapadakou

Nancy Z Zhou

Rebecca T Ruck

Christopher J Mortko

Frank Dininno

Barry R Cunningham

Kevin Dykstra

Jubrail Rahl

Substituted bicyclic beta-lactams of Formula I: (I), are &#x3b2;-lactamase inhibitors, wherein a, X, Rand Rare defined herein. The compounds and pharmaceutically acceptable salts thereof are useful in the treatment of bacterial infections in combination with &#x3b2;-lactam antibiotics. In particular, the compounds can be employed with a &#x3b2;-lactam antibiotics (e.g., imipenem, piperacillin, or ceftazidime) against microorganisms resistant to &#x3b2;-lactam antibiotics due to the presence of the &#x3b2;-lactamases.

&#x3b2;-lactamase inhibitors

This invention provides novel &#x3b2;-lactamase inhibitors of the aryl- and heteroaryl-sulfonamidomethylphosphonate monoester class having nitrogen-based cations or quarternary ammomium groups. The compounds inhibit three classes of &#x3b2;-lactamases and synergize the antibacterial effects of &#x3b2;-lactam antibiotics (e.g., imipenem and ceftazimdime) against those micro-organisms normally resistant to the &#x3b2;-lactam antibiotics as a result of the presence of the &#x3b2;-lactamases.

Inhibitors of beta-lactamase

The present invention features alethal factor substrate. The substrate can be used for example to measure lethal factor activity. Preferred substrates contain one or mare detectable labels and have a sufficiently high turnover rate for applications in a high throughput screen.

Reagents for assaying Bacillus anthracis lethal factor protease

Provided is a method of identifying agonists and antagonists of nuclear receptors that comprises measuring agonist-dependent fluorescence resonance energy transfer (FRET) between a fluorescently labeled nuclear receptor or ligand binding domain and fluorescently labeled CREB-binding protein (CBP), p300, other nuclear co-activator, or binding portion thereof. The method is simple, rapid, and inexpensive. Nuclear receptors and nuclear receptor co-activators labeled with fluorescent reagents for use in the above-described method are also provided.

Assays for nuclear receptor agonists and antagonists using fluorescence resonance energy transfer

Compounds of the formula ##STR1## are inhibitors of peptide binding to major histocompatibility complex type II proteins and are useful in the treatment and prevention of autoimmune diseases including: rheumatoid arthritis, Type I diabetes, multiple sclerosis, lupus erythematosis, Graves disease and pemphigus. The present invention also provides novel compositions, methods of treatment employing the compounds of the present invention and methods of manufacture of the compounds of structural formula (I).

Pseudopeptide lactam inhibitors of peptide binding to MHC class II

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Warren, NJ, United States of America

Jeffrey Donald Hermes