1-OXO- ET 1,3-DIOXOISOINDOLINES SUBSTITUEES ET LEUR UTILISATION DANS DES COMPOSITIONS PHARMACEUTIQUES AFIN DE REDUIRE LES TAUX DE CYTOKINES INFLAMMATOIRES
1-Oxo- and 1,3-dioxoisoindolines substituted inthe 4- or 5-position of the indoline ring reduce the levelsof inflammatory cytokines such as TNF.alpha. in a mammal. Thus,in one aspect, the invention provides a compound of theformula:(see formula I)in which: the carbon atom designated C* constitutes acenter of chirality when n is not zero and when R1 is not R2；one of X1 and X2 is nitro, alkyl of one to six carbons, orNH-Z, and the other of X1 or X2 is hydrogen； each of R1 and R2independent of the other, is hydroxy or NH-Z； R3 is hydrogen,alkyl of one to six carbons, or halo； Z is hydrogen, aryl,an acyl of one to six carbons, or an alkyl of one to sixcarbons； and n has a value of 0, 1, or 2； provided that ifone of X1 and X2 is nitro, and n is 1 or 2, then R1 and R2 areother than hydroxy； and the salts thereof. In anotheraspect, the invention provides a compound of the formula:(see formula II)in which: the carbon atom designated C* constitutes acenter of chirality when n is not zero and R1 is not R2； oneof X1 and X2 is amino, nitro, alkyl of one to six carbons, orNH-Z, and the other of X1 or X2 is hydrogen； each of R1 and R2independent of the other, is hydroxy or NH-Z； R3 is alkyl ofone to six carbons, halo, or hydrogen； Z is hydrogen, aryl,an acyl of one to six carbons, or an alkyl of one to sixcarbons； n has a value of 0, 1, or 2； provided that if oneof X1 and X2 is amino or nitro, one of X1 and X2 is hydrogen,and n is 1 or 2, then R1 and R2 are not both hydroxy； and thesalts thereof. A typical embodiment is 4-(4-amino-1,3-dioxoisoindolin-2-yl)-4-carbamoylbutanoic acid.
