Affymax Technologies, N.v.

Other

Glaxo Wellcome Inc.

Glaxo Group Limited

Burroughs Wellcome, Inc.

David A Campbell

Dinesh Vinoobhai Patel

Xiao-Yi Xiao

Anna Katrin Szardenings

Gary Charles Look

Harold E Selick

Valery V Antonenko

Mark A Gallop

Jeffrey William Jacobs

Arthur H Muir

Robert M Gavin

Todd T Romoff

Satoru Ida

Disclosed are novel inhibitors of metalloproteases, in particular matrix metalloproteases. The disclosed inhibitors are mercaptoketone and mercaptoalcohol compounds which are useful in pharmaceutical compositions and methods for treating or controlling disease states or conditions which involve tissue breakdown, for example, arthropathy, dermatological conditions, bone resorption, inflammatory diseases, and tumor invasion and in the promotion of wound healing.

Inhibitors of metalloproteases, pharmaceutical compositions comprising same and methods of their use

Novel inhibitors of metalloproteases, in particular collagenase-1 and stromelysin-1, are disclosed. Such compounds are useful in pharmaceutical compositions and methods for treating or controlling disease states or conditions which involve tissue breakdown, such as rheumatoid arthritis.

Collagenase-1 and stromelysin-1 inhibitors, pharmaceutical compositions comprising same and methods of their use

The invention provides a system and method for synthesizing chemicals onto supports in a parallel manner to produce a combinatorial collection of compounds. The system includes a plurality of middle plates, with each middle plate defining a plurality of reaction zones arranged in a two dimensional array. The reaction zones are adapted to receive a solid support, such as a sheet of membrane, and the middle plates are stackable on each other to form a three dimensional array of reaction zones. The system also includes a pair of end plates, where the middle plates are located between the end plates, and where the end plates include an array of fluid guides corresponding to the array of reaction zones, to allow for selective routing of reagents through the reaction zones.

System and method for solid-phase parallel synthesis of a combinatorial collection of compounds

System and method for solid-phase parallel synthesis of a combinatorial

It is known that the human influenza virus strain A/Puerto Rico/8/34 grows particularly well in eggs and that reasserted viruses having it as a parent may also grow well in eggs. It has now been found that certain reassortants of A/PR/8/34 and equine influenza viruses, namely those which comprise the RNA7 segment from A/PR/8/34, will grow in cell culture, even though the parent equine influenza virus will not. Thus the specification describes and claims: reassorted viruses comprising genes for surface antigens of equine influenza viruses and the RNA7 segment from A/PR/8/34; methods of obtaining such viruses by reassortment; methods of propagating such reasserted viruses in cell culture, especially Vero cells; vaccines against equine influenza comprising such reassorted viruses; and methods of vaccinating equines against influenza.

Vaccines for equine influenza

Novel inhibitors of metalloproteases are disclosed. Such compounds are useful in pharmaceutical compositions and methods for treating or controlling disease states or conditions which involve tissue breakdown, such as rheumatoid arthritis.

Inhibitors of metalloproteases pharmaceutical compositions comprising

Novel inhibitors of metalloproteases, in particular collagenase-1 and stromelysin-1, are disclosed. Such compounds are useful in pharmaceutical compositions and methods for treating or controlling disease states or conditions which involve tissue breakdown, such as rheumatoid arthritis. ##STR1##

Collagenase-1 and stromelysin-1 inhibitors, pharmaceutical compositions

Inhibitors of metalloproteases, pharmaceutical compositions comprising

Disclosed are methods for synthesizing very large collections of diverse diverse tetramic acids, tetronic acids, pentamic acids, pentonic acids, and derivatives thereof and synthetic compound libraries comprising compounds prepared by such methods.

Methods for synthesizing diverse collections of tetramic acids and

Disclosed are novel inhibitors of collagenase-1 and stromelysin-I metalloproteases. The disclosed inhibitors are mercaptoketone and mercaptoalcohol compounds which are useful in pharmaceutical compositions and methods for treating or controlling disease states or conditions which involve tissue breakdown, for example, arthropathy, dermatological conditions, bone resorption, inflammatory diseases, and tumor invasion and in the promotion of wound healing.

Inhibitors of collagenase-1 and stormelysin-I metalloproteases,

The present invention relates to the areas of organic and medicinal chemistry. More specifically, the present invention is concerned with combinatorial and solid phase methods for the synthesis of diverse diketopiperazine derivatives, and the use of such methods to create libraries of diverse diketopiperazine derivatives. The present invention has application in the areas of chemical synthesis, the screening for new diketopiperazine derivatives having beneficial medical properties and the use of such screening to provide compositions and methods including diketopiperazine derivatives for treating disease.

Method for synthesis of diketopiperazine and diketomorpholine derivatives

Phsophonate esters can be synthesized in high yields by condensations of alcohols with methyl phosphonates followed by selective demethylation. The reaction is general, relativly insensitive to steric constraints of hindered phosphonic acids, and can also be carried out on a solid support to synthesize large collections of compounds to screen for pharmacological activity.

Methods for the synthesis of phosphonate esters

A stereospecific method of preparing alpha-aminophosphonic acids and derivatives thereof is provided. A protected amino acid is converted to a acyl aroyl or diacyl peroxide which spontaneously rearranges to form an alpha-amino ester. This rearrangement occurs stereospecifically with retention of configuration. The ester is subsequently converted to an appropriate leaving group and displaced with a phosphite yielding a chiral alpha-aminophosphonic acid or derivative. Alpha-aminophosphonic acids are useful for the synthesis of peptide analogs that possess a phosphonate linkage in the place of an amide linkage. This substitution can impart protease resistance in therapeutic peptides thereby increasing the serum half-life.

Chiral synthesis of alpha-aminophosponic acids

Phosphonate esters can be synthesized in high yields by condensations of alcohols with methyl phosphonates followed by selective demethylation. The reaction is general, relatively insensitive to steric constraints of hindered phosphonic acids, and can also be carried out on a solid support to synthesize large collections of compounds to screen for pharmacological activity.

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San Mateo, CA, United States of America

David A Campbell