Substituted acylhydroxamic acids and method of reducing TNFalpha levels

An acylhydroxamic acid derivative selected from the group consisting of

• (a) compounds of the formula:
• 6
• wherein
• the carbon atom designated * constitutes a center of chirality,
• R4 is hydrogen or —(C═O)—R12;
• each of R1 and R12, independently of each other, is alkyl of 1 to 6 carbon atoms, phenyl, benzyl, pyridyl methyl, pyridyl, imidazoyl, imidazolyl methyl, or CHR*(CH2),NR*R0
• wherein R*and R0, independently of the other, are hydrogen, alkyl of 1 to 6 carbon atoms, phenyl, benzyl, pyridylmethyl, pyridyl, imidazoyl or imidazolylmethlyl, and n=0, 1, 2;
• R5 is C═O, CH2, CH2—CO—, or SO2;
• each of R6 and R7, independently of the other, is nitro, cyano, trifluoromethyl, carbethoxy, carbomethoxy, carbopropoxy, acetyl, carbamoyl, acetoxy, carboxy, hydroxy, amino, alkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, cycloalkoxy of 3 to 8 carbon atoms, halo, bicycloalkyl of up to 18 carbon atoms, tricycloalkoxy of up to 18 carbon atoms, 1-indanyloxy, 2-indanyloxy, C4-C8-cycloalkylidenemethyl, or C3-C10-alkylidenemethyl;
• each of R8, R9, R10, and R11, independently of the others, is
• (i) hydrogen, nitro, cyano, trifluoromethyl, carbethoxy, carbomethoxy, carbopropoxy, acetyl, carbamoyl, acetoxy, carboxy, hydroxy, amino, aikylamino, dialkylamino, acylamino, alkyl of 1 to 10 carbon atoms, alkoxy of 1 to 10 carbon atoms, halo, or
• (ii) one of R8, R9, R10, and R11 is acylamino comprising a lower alkyl, and the remaining of R8, R9, R10, and R11 are hydrogen, or
• (iii) hydrogen if R8 and R9 taken together are benzo, quinoline, quinoxaline, benzimidazole, benzodioxole, 2-hydroxybenzimidazole, methylenedioxy, dialkoxy, or dialkyl, or
• (iv) hydrogen if R10 and R11, taken together are benzo, quinoline, quinoxaline, benzimidazole, benzodioxole, 2-hydroxybenzimidazole, methylenedioxy, dialkoxy, or dialkyl, or
• (v) hydrogen if R9 and R10 taken together are benzo;
• and
• (b) The acid addition salts of said compounds which contain a nitrogen atom capable of being protonated.