Substituted alkanohydroxamic acids and method of reducing TNFalpha levels

A substantially chirally pure (R)— or a substantially chirally pure (S)—, or mixture of (R)— and (S)— hydroxamic acid derivative selected from the group consisting of (a) compounds of the formula:

• 6
• wherein
• each of R1 and R2, when taken independently of each other, is hydrogen, lower alkyl, or R1 and R2, when taken together, together with the depicted carbon atoms to which each is bound, is o-phenylene, o-naphthylene, or cyclohexene-1,2-diyl, unsubstituted or substituted with 1 to 4 substituents each selected independently from the group consisting of nitro, cyano, trifluoromethyl, carbethoxy, carbomethoxy, carbopropoxy, acetyl, carbamoyl, acetoxy, carboxy, hydroxy, amino, alkylamino, dialkylamino, acylamino, alkyl of 1 to 10 carbon atoms, alkoxy of 1 to 10 carbon atoms, cycloalkoxy of 3 to 6 carbon atoms, C4-C6-cycloalkylidenemethyl, C3-C10-alkylidenemethyl, indanyloxy, and halo;
• R3 is phenyl substituted with from one to four substituents selected from the group consisting of nitro, cyano, trifluoromethyl, carbethoxy, carbomethoxy, carbopropoxy, acetyl, carbamoyl, acetoxy, carboxy, hydroxy, amino, alkyl of 1 to 10 carbon atoms, alkoxy of 1 to 10 carbon atoms, cycloalkoxy of 3 to 6 carbon atoms, and halo;
• or C4-C6-cycloalkylidenemethyl, C3-C10-alkylidenemethyl;
• and
• R4 is hydrogen, alkyl of 1 to 10 carbon atoms, phenyl, or benzyl;
• R4 is hydrogen or alkyl of 1 to 6 carbon atoms;
• R5 is —CH2—, —CH2—CO—, —CO—, —SO2—, —S—, or —NHCO—;
• and
• n has a value of 0, 1, or 2;
• and
• (b) the acid addition salts of said compounds which contain a nitrogen atom capable of being protonated.