| 摘要 |
The invention provides an effective amount of a diketopiperazine having the following formula for use in the treatment of a T-cell mediated autoimmune disease:
wherein:
R 1 and R 2 , which may be the same or different, each is:
(a) a side chain of an amino acid, wherein the amino acid is glycine, alanine, valine, norvaline, ±-aminoisobutyric acid, 2,4-diaminobutyric acid, 2,3-diaminobutyric acid, leucine, isoleucine, norleucine, serine, homoserine, threonine, aspartic acid, asparagine, glutamic acid, glutamine, lysine, hydroxylysine, histidine, arginine, homoarginine, citrulline, phenylalanine, p-aminophenylalanine, tyrosine, thyroxine, cysteine, homocysteine, methionine, penicillamine or ornithine; provided, however, that when R 1 is the side chain of asparagine or glutamine, then R 2 cannot be the side chain of lysine or ornithine, and when R 1 is the side chain of lysine or ornithine, then R 2 cannot be the side chain of asparagine or glutamine;
(b) a derivative of a side chain of an amino acid, wherein the amino acid is one of those recited in (a), and the derivatized side chain has:
(i) an -NH 2 group replaced by an -NHR 3 or -N(R 3 ) 2 group, wherein each R 3 may independently be a substituted or unsubstituted alkyl, cycloalkyl, heterocycloalkyl, aryl, alkylaryl, arylalkyl or heteroaryl;
(ii) an -OH group replaced by an -O-PO 3 H 2 or -OR 3 group, wherein each R 3 may independently be a substituted or unsubstituted alkyl, cycloalkyl, heterocycloalkyl, aryl, alkylaryl, arylalkyl or heteroaryl;
(iii) a -COOH group replaced by a -COOR 3 group, wherein each R 3 may independently be a substituted or unsubstituted alkyl, cycloalkyl, heterocycloalkyl, aryl, alkylaryl, arylalkyl or heteroaryl;
(iv) a -COOH group replaced by a -CON(R 4 ) 2 group, wherein each R 4 may independently be H or a substituted or unsubstituted alkyl, cycloalkyl, heterocycloalkyl, aryl, alkylaryl, arylalkyl or heteroaryl;
(v) an -SH group replaced by -S-S-CH 2 -CH(NH 2 )-COOH or -S-S-CH 2 -CH 2 -CH(NH 2 )-COOH;
(vi) a -CH 2 - group replaced by a -CH(NH 2 )- or a -CH(OH)- group;
(vii) a -CH 3 group replaced by a -CH 2 -NH 2 or a -CH 2 -OH group; and/or
(viii) an H which is attached to a carbon atom replaced by a halogen; or
a physiologically-acceptable salt thereof. |
