Vertex Pharmaceuticals, Inc.

Roussel Uclaf

Saroop Singh Matharu

David J Lauffer

Guy W Bemis

Mark Andrew Murcko

Michael D Mullican

David Bebbington

Robert E Zelle

David J Livingston

Mark James Batchelor

Wolf Herman Fridman

Robert Murdoch

Roger John Gillespie

Julian M C Golec

Keith P Wilson

Michael Su

Philip L Nyce

Andrea L C Robidoux

M Woods Wannamaker

Yong Gu

Julian M Golec

David A Rowlands

Robert Westwood

John Bodenham Taylor

Peter Wilfred Hairsine

The present invention relates to novel classes of compounds which are inhibitors of interleukin-1&#x3b2; converting enzyme. The ICE inhibitors of this invention are characterized by specific structural and physicochemical features. This invention also relates to pharmaceutical compositions comprising these compounds. The compounds and pharmaceutical compositions of this invention are particularly well suited for inhibiting ICE activity and consequently, may be advantageously used as agents against IL-1-, apoptosis-, IGIF-, and IFN-&#x3b3;-mediated diseases, inflammatory diseases, autoimmune diseases, destructive bone disorders, proliferative disorders, infectious diseases, degenerative diseases, and necrotic diseases. This invention also relates to methods for inhibiting ICE activity, for treating interleukin-1-, apoptosis-, IGIF- and IFN-&#x3b3;-mediated diseases and decreasing IGIF and IFN-&#x3b3; production using the compounds and compositions of this invention. This invention also relates to methods for preparing N-acylamino compounds.

Inhibitors of interleukin-1&#x3b2; converting enzyme

The present invention relates to novel classes of compounds which are inhibitors of interleukin-1&#x3b2; converting enzyme. The ICE inhibitors of this invention are characterized by specific structural and physicochemical features. This invention also relates to pharmaceutical compositions comprising these compounds. The compounds and pharmaceutical compositions of this invention are particularly well suited for inhibiting ICE activity and consequently, may be advantageously used as agents against IL-1-, apoptosis-, IGIF-, and IFN-&#x3b3;-mediated diseases, inflammatory diseases, autoimmune diseases, destructive bone disorders, proliferative disorders, infectious diseases, degenerative diseases, and necrotic diseases. This invention also relates to methods for inhibiting ICE activity, for treating interleukin-1-, apoptosis-, IGIF- and IFN-&#x3b3;-mediated diseases and decreasing IGIF and IFN-&#x3b3; production using the compounds and compositions of this invention. This invention also relates to methods for preparing-N-acylamino compounds.

The present invention relates to novel classes of compounds which are inhibitors of interleukin-1&bgr; converting enzyme. The ICE inhibitors of this invention are characterized by specific structural and physicochemical features. This invention also relates to pharmaceutical compositions comprising these compounds. The compounds and pharmaceutical compositions of this invention are particularly well suited for inhibiting ICE activity and consequently, may be advantageously used as agents against IL-1-, apoptosis-, IGIF-, and IFN-&ggr;-mediated diseases, inflammatory diseases, autoimmune diseases, destructive bone disorders, proliferative disorders, infectious diseases, degenerative diseases, and necrotic diseases. This invention also relates to methods for inhibiting ICE activity, for treating interleukin-1-, apoptosis-, IGIF- and IFN-&ggr;-mediated diseases and decreasing IGIF and IFN-&ggr; production using the compounds and compositions of this invention. This invention also relates to methods for preparing N-acylamino compounds.

Inhibitors of interleukin-1&bgr; converting enzyme

The present invention relates to novel classes of compounds which are inhibitors of interleukin-IB converting enzyme. The ICE inhibitors of this invention are characterized by specific structural and physicochemical features. This invention also relates to pharmaceutical compositions comprising these compounds. The compounds and pharmaceutical compositions of this invention are particularly well suited for inhibiting ICE activity and consequently, may be advantageously used as agents against IL-1-, apoptosis-, IGIF-, and IFN-&ggr;-mediated diseases, inflammatory diseases, autoimmune diseases, destructive bone disorders, proliferative disorders, infectious diseases, degenerative diseases, and necrotic diseases. This invention also relates to methods for inhibiting ICE activity, for treating interleukin-1-, apoptosis-, IGIF- and IFN-&ggr;-mediated diseases and decreasing IGIF and IFN-&ggr; production using the compounds and compositions of this invention. This invention also relates to methods for preparing N-acylamino compounds.

Inhibitors of Interleukin-1&bgr; converting enzyme

The present invention relates to pyradazino&lsqb;1,2-a&rsqb;&lsqb;1,2&rsqb;diazepine-1-carboxamide compounds of formula:

Inhibitors of interleukin-1&bgr; Converting enzyme inhibitors

The present invention relates to novel classes of compounds which are inhibitors of interleukin-1.beta. converting enzyme. The ICE inhibitors of this invention are characterized by specific structural and physicochemical features. This invention also relates to pharmaceutical compositions comprising these compounds. The compounds and pharmaceutical compositions of this invention are particularly well suited for inhibiting ICE activity and consequently, may be advantageously used as agents against an IL-1 mediated disease, an apoptosis mediated disease, AML, CML, melanoma, myeloma, Kaposi's sarcoma, graft vs host disease, rheumatoid arthritis, inflammatory bowel disorder, psoriasis, osteoarthritis, myeloma, apoptosis, sepsis, rheumatoid arthritis, asthma, Alzheimer's disease, Parkinson's disease, and ischemic heart disease diseases. This invention also relates to methods for inhibiting ICE activity and methods for treating interleukin-1 mediated diseases using the compounds and compositions of this invention.

Inhibitors of interleukin-1.beta. converting enzyme

Novel pyrimido[2,1-b]benzothiazoles of the formula ##STR1## wherein R and R.sub.3 are individually selected from the group consisting of hydrogen and alkyl of 1 to 6 carbon atoms or taken together with the carbon to which they are attached form a cycloalkyl of 3 to 6 carbon atoms, R.sub.1 is selected from the group consisting of hydroxy, alkoxy of 1 to 12 carbon atoms, cycloalkyl of 7 to 12 carbon atoms, and ##STR2## R.sub.5 and R.sub.6 are individually selected from the group consisting of hydrogen and alkyl of 1 to 6 carbon atoms or taken together with the nitrogen form piperidino or morpholino, R.sub.2 is selected from the group consisting of hydrogen, alkyl of 1 to 6 carbon atoms, alkoxycarbonyl of 2 to 7 carbon atoms, cycloalkyl of 3 to 6 carbon atoms, heteroaryl, aralkyl and optionally substituted aryl with at least one substituent selected from the group consisting of halogen, nitro, and alkyl and alkoxy of 1 to 6 carbon atoms and their salts with non-toxic, pharmaceutically acceptable acids and bases having antiallergic activity.

Pyrimido[2,1-b]benzothiazoles having antiallergic activity

The present invention relates to derivatives of hexahydrodibenzofuran-3-one and their salts possessing interesting antitussive activity, their process of preparation, intermediates, and pharmaceutical compositions.

Derivatives of hexahydrodibenzofuran-3-one, their preparation and use in

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Cricklade, United Kingdom

Saroop Singh Matharu