| 摘要 |
1-Oxo- and 1,3-dioxoisoindolines substituted in the 4- or 5-position of the indoline ring reduce the levels of inflammatory cytokines such as TNF.alpha. in a mammal. Thus, in one aspect, the invention provides a compound of the formula: (see formula I) in which: the carbon atom designated C* constitutes a center 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, or NH-Z, and the other of X1 or X2 is hydrogen; each of R1 and R2 independent 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 six carbons; and n has a value of 0, 1, or 2; provided that if one of X1 and X2 is nitro, and n is 1 or 2, then R1 and R2 are other than hydroxy; and the salts thereof. In another aspect, the invention provides a compound of the formula: (see formula II) in which: the carbon atom designated C* constitutes a center of chirality when n is not zero and R1 is not R2; one of X1 and X2 is amino, nitro, alkyl of one to six carbons, or NH-Z, and the other of X1 or X2 is hydrogen; each of R1 and R2 independent of the other, is hydroxy or NH-Z; R3 is alkyl of one to six carbons, halo, or hydrogen; Z is hydrogen, aryl, an acyl of one to six carbons, or an alkyl of one to six carbons; n has a value of 0, 1, or 2; provided that if one of 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 the salts thereof. A typical embodiment is 4-(4-amino-1,3-dioxoisoindolin-2-yl)-4-carbamoylbutanoic acid.
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