Vertex Pharmaceuticals, Inc.

Sanofi

Sterling Winthrop Inc.

Sanofi Winthrop Inc.

Denton W Hoyer

Roland Ellwood Dolle

Tina Morgan Ross

Stanley J Schmidt

James M Rinker

Mark A Ator

Prasad V Chaturvedula

Jasbir Singh

Mohamed M Awad

Joseph M Salvino

Robert A Snow

Catherine P Prouty

David L Ladd

Irennegbe K Osifo

Catherine Prouty

David A Whipple

Eric P Lodge

Mohamed M A Awad

Disclosed are compounds of the formula (I) and pharmaceutically acceptable salts thereof:wherein

4-pyridazinecarboxamides and esters as interleukin-1&#x3b2;  converting enzyme inhibitors

Pyridazines as interleukin-1&bgr; converting enzyme inhibitors

Disclosed are compounds, compositions, and methods for inhibiting interleukin-1&bgr; protease activity, wherein the compounds are &agr;-substituted methyl ketones having formula (I) as set forth herein. These compounds are inhibitors of IL-1&bgr; converting enzyme and as such are useful as therapeutic agents for certain infectious diseases.

Peptide analogs as irreversible interleukin-1&bgr; protease inhibitors

Disclosed are compounds of the formula (I) and pharmaceutically acceptable salts thereof: ##STR1## wherein R.sub.1 is a halogen, or an oxygen linked leaving group including an aromatic ether, an alkyl sulfonate, an aryl sulfonate, an alkyl phosphonate, an aryl phosphonate, an alkyl phosphate or aryl phosphate;

Pyridazines as interleukin-1.beta. converting enzyme inhibitors

Disclosed are compounds, compositions and methods for inhi.beta.iting interleukin-1.beta. protease activity, the compounds .alpha.-substituted methyl ketones having the formula (I) set forth herein. These compounds are inhibitors of IL-1.beta. converting enzyme and as such are useful as therapeutic agents for certain infectious diseases.

Peptide analogs as irreversible interleukin-1.beta. protease inhibitors

Compounds which Inhibit interleukin-1.beta. protease activity, pharmaceutical compositions containing the compounds and methods using the compounds are provided. The compounds have the formula ##STR1## wherein n is 0-2; each AA is Independently L-valine or L-alanine; R.sub.1 is selected from the group consisting of N-�4(N,N-dimethylaminomethyl)!benzoyl, N-benzoyloxycarbonyl, N-methyl-N-�4-(pyridyl)methyl!, N-�4-(pyddyl)methyl!carbonyl, N-3-(piperidinopropionyl), N-�4-(morpholinoethoxy)benzoyl, N-2-(quinuclidinyl)carbonyl, N-(3-pyridyl)methoxy carbonyl, N-(2-pyddyl)methoxy carbonyl, N-methyl-N-benzyl carbonyl, N-methyl-N-�2-(4-pyridyl)ethyl!carbonyl, and N-(N-phenylpiperazino) carbonyl; and R.sub.8, R.sub.9 and R.sub.10 are as defined below.

.alpha.-heteroaryloxymethyl ketones as interleukin - 1 .beta. converting

Disclosed are pharmaceutical compositions containing low diol polyethylene glycol, covalently attached to superoxide and dismutase process of making the compositions. Also disclosed is a method of treatment of disease processes associated with the adverse effects on tissue of superoxide anions, such as ischemic events, reperfusion injury, trauma and inflammation.

Low diol polyalkylene oxide biologically active proteinaceous substances

Compounds which inhibit interleukin-1.beta. protease activity, pharmaceutical compositions containing the compounds and methods using the compounds are provided. The compounds have the formula ##STR1## wherein n is 0-2; each AA is independently L-valine or L-alanine; R.sub.1 is selected from the group consisting of N-[4-(N,N-dimethylaminomethyl)]benzoyl, N-benzyloxycarbonyl, N-methyl-N-[4-(pyridyl)methyl], N-[4-(pyridyl)methyl]carbonyl, N-3-(piperidinopropionyl), N-[4-(morpholinoethoxy)benzoyl, N-2-(quinuclidinyl)carbonyl, N-(3-pyridyl)methoxy carbonyl, N-(2-pyridyl)methoxy carbonyl, N-methyl-N-benzyl carbonyl, N-methyl-N-[2-(4-pyridyl)ethyl]carbonyl, and N-(N-phenylpiperazino)carbonyl; and R.sub.8, R.sub.9, R.sub.10 are each independently hydrogen, lower alkyl, halo substituted methyl, carbalkoxy, benzyl, phenyl, or phenyl mono or disubstituted with fluoro, nitro, methoxy, chloro, trifluoromethyl or methanesulfonyl.

Heteroaryloxymethyl ketones as interleukin-1.beta.converting enzyme

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Exton, PA, United States of America

Denton W Hoyer