Heteroaryloxymethyl ketones as interleukin-1.beta.converting enzyme inhibitors

A pharmaceutical composition for inhibiting interleukin-1.beta. protease activity comprising an effective inhibitory amount of a compound of the formula:

• ##STR15## or a pharmaceutically acceptable salt thereof, wherein n is 0-2;
• 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 and 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, in a pharmaceutically acceptable carrier.

A method for inhibiting interleukin-1.beta. protease activity in a mammal in need of such treatment comprising administering to said mammal an effective interleukin-1.beta. protease inhibitory amount of a pharmaceutical composition comprising a compound of the formula:

• ##STR16## or a pharmaceutically acceptable salt thereof, wherein n is 0-2;
• 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-benzylcarbonyl,
• 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 each independently hydrogen, lower alkyl, halo substituted methyl, carbalkoxy, benzyl, phenyl, or phenyl mono or disubstituted with fluoro, nitro, methoxy, chloro, trifluoromethyl or methanesulfonyl, in a pharmaceutically acceptable carrier.