Pyridazines as interleukin-1beta converting enzyme inhibitors

A pharmaceutical composition for inhibiting interleukin-1β protease comprising the formula (I) or a pharmaceutically acceptable salt thereof

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• wherein
• R1, is halogen, aromatic ether, alkyl sulfonate, aryl sulfonate, alkyl phosphonate, aryl phosphonate, alkyl phosphate or aryl phosphate;
• R2 is COOR5, C(=0)NH(CHR5)m—COOR5, NH(CHR5)mCON(R5)R6, C(=0)N(R5)R6 or NH(CHR5)mOH;
• R3 is H or alkyl;
• R4 is H, substituted or unsubstituted aryl, heteroaryl or alkyl;
• R5 and R6 are independently H, lower alkyl, aryl, hydroxy alkyl, amio alkyl, heteroaryl, lower alkylene-aryl, lower alkylene-heteroaryl or lower cycoalkyl;
• and m is 0-6 in a pharmaceutically acceptable carrier.

A method of inhibiting interleukin-1β protease activity in a mammal in need of such treatment comprising administering to said mammal an effective inhibitory amount of a pharmaceutical composition comprising a compound of the formula (I) or a pharmaceutically acceptable salt thereof:

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• wherein
• R1 is halogen, aromatic ether, alkyl sulfonate, aryl sulfonate, alkyl phosphonate, aryl phosphonate, alkyl phosphate or aryl phosphate;
• R2 is COOR5, C(=0)NH(CHR5)m—COOR5, NH(CHR5)mCON(R5)R6, C(=0)N(R5)R6 or NH(CHR5)mOH;
• R3 is H or alkyl;
• R4 is. H, substituted or unsubstituted aryl, heteroaryl or alkyl;
• R5 and R6 are independently H, lower alkyl, aryl, hydroxy alkyl, amio alkyl, heteroaryl, lower alkylene-aryl, lower alkylene-heteroaryl or lower cycoalkyl;
• and m is 0-6 in a pharmaceutically acceptable carrier.