Pharmacopeia Inc.

Bristol-Myers Squibb Compnay

Yvonne Class Shimshock

Roland Ellwood Dolle

Timothee Felix Herpin

Carolyn DiIanni Carroll

John J Baldwin

Katerina Leftheris

Alaric J Dyckman

Stephen T Wrobleski

Shawn David Erickson

Wei Li

Edward McDonald

Jeffrey John Letourneau

Ian Henderson

Axel Metzger

Kevin Joseph Moriarty

Gulzar Ahmed

Cullen Lee Cavallaro

Zahid Hussain

James Wen

Junjun Wu

Edward Mcdonald

N-heterocyclic compounds that block cytokine production via inhibition of p38 kinase are disclosed. In one embodiment, compounds of the present invention are represented by Formula I:  Methods of production, pharmaceutical compositions and methods of treating conditions associated with inappropriate p38 kinase activity or TNF-&#x3b1; expression utilizing compounds of the present invention are also disclosed.

N-heterocyclic inhibitors of TNF-&#x3b1; expression

N-heterocyclic compounds that block cytokine production via inhibition of p38 kinase are disclosed. In one embodiment, compounds of the present invention are represented by Formula I: Methods of production, pharmaceutical compositions and methods of treating conditions associated with inappropriate p38 kinase activity or TNF-&#x3b1; expression utilizing compounds of the present invention are also disclosed.

Glycol and hydroxyphosphonate peptidomimetics as inhibitors of aspartyl proteases

Combinatorial chemical libraries of the Formula &lsqb;S&rsqb;&mdash;C(O)&mdash;L&prime;&mdash;Z containing dihyroxy amides and hydroxyphosphonate amides are disclosed, in which &lsqb;S&rsqb; represents a solid support and &mdash;L&prime;&mdash;Z is a linker/ligand residue. In these libraries, Z is

Process for preparing combinatorial amide alcohol libraries

Compounds of Formula I ##STR1## are disclosed as inhibitors having activity against the aspartyl proteases, plasmepsin and cathepsin D. The compounds are therefore useful for treatment of diseases such as malaria and Alzheimer's disease. In preferred compounds of Formula I, Y is an dialkoxyphosphonate, or .alpha.-hydroxyamide group and Z is an acyl or .alpha.-ketocarbamate functionality. Intermediates in the solid phase synthesis of compounds of Formula I, in which compounds are attached to a solid support, are also disclosed.

Hydroxyphosphonate peptidomimetics as inhibitors of aspartyl proteases

Combinatorial chemical libraries of the Formula [S]-C(O)-L'-Z containing dihyroxy amides and hydroxyphosphonate amides are disclosed, in which [S] represents a solid support and -L'-Z is a linker/ligand residue. In these libraries, Z is ##STR1## and Y is --P(O)(OR.sup.6)(OR.sup.7), --CH(OH)--COR.sup.8, --CH.sub.2 CH.dbd.CH.sub.2 --CH.sub.2 CH(OH)CH.sub.2 OH, --CH.sub.2 CHO, --CH.sub.2 CH.sub.2 OH, --CH.sub.2 CH.sub.2 OC(O)NHR.sup.26, --CH.sub.2 CH.sub.2 NR.sup.27 R.sup.28, or ##STR2## The combinatorial libraries are optionally encoded with tags. The use of these libraries in assays to discover biologically active compounds is also disclosed.

Combinatorial amide alcohol libraries

Glycol and hydroxyphosphonate peptidomimetics as inhibitors of aspartyl

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Somerville, NJ, United States of America

Yvonne Class Shimshock