| abstract |
The specification describes compounds which are useful as inhibitors of matrix metalloproteases, and which are effective in treating conditions characterized by excess activity of these enzymes. The compounds have a compound having a structure according to Formula (I) wherein: R1 is hydrogen, alkyl, aryl-alkyl, heterocycle-alkyl, alkoxy-alkyl, arylalkoxy-alkyl, or alkylthioalkyl; R2 is hydrogen, alkyl, aryl-alkyl, heterocycle-alkyl, alkoxy-alkyl, arylalkoxy-alkyl, or alkylthioalkyl; R3 is alkyl, cycloalkyl, carbocyclic or heterocyclic aryl, hydroxyalkyl, alkoxyalkyl, or aminoalkyl; and R4 is carbocyclic or heterocyclic aryl; an optical isomer, diastereomer or enantiomer thereof, or a pharmaceutically-acceptable salt, or biohydrolyzable alkoxyamide, ester acyloxyamide, or imide thereof. Preferred R4 include phenyl and substituted phenyl. Preferred substitution on R4 is adjacent to the attachment or opposite to it (i.e., if R4 is phenyl, then at the 2 and/or 4 positions). Preferred phenyl substituents include halo, alkyl, alkoxy, nitro, cyano and the like. Preferred R3 are alkyl, more preferably C1-C2 alkyl. Preferred R2 are H or alkyl, more preferably H or C1-C4 alkyl. Preferred R l are H or alkyl, arylalkyl, more preferably C1-C6 alkyl, or aryl (C1-C2) alkyl. These compounds have the ability to inhibit at least one mammalian matrix metalloprotease. |