Amino acid derivatives of triptolide compounds as immune modulators and anticancer agents

摘要

Compounds which are prodrugs of triptolide or its derivatives, containing an amino acid or oligopeptide moiety, are used for anticancer or immunosuppressive treatment. The compounds are of the structure: where X1 is OH or OR1, and X2 and X3 are independently OH, OR1 or H, with the proviso that at least one of X1, X2 and X3 is OR1, and at least one of X2 and X3 is H; and R1, is selected from the group consisting of: (b): C(=O)CHY-NHP1 (c): C(=O)CH(NHP1)-(CH2)m-C(=O)OP2 (d): C(=O)(CH2)n-CH(NHP1)-C(=O)OP2 and (e): [C(=O)CHY-NH]Z-C(=O)CHY-NHP1; where Y is a side chain of a naturally occurring amino acid or a one- or two-carbon homolog thereof; P1 is selected from the group consisting of H, C(=O)OR2, and C(=O)R3, where each of R2 and R3 is independently H, alkyl, alkenyl, aryl, or aralkyl; m is an integer from 0-5; n is an integer from 0-5; z is an integer from 2-10; and P2 is selected from the group consisting of H, alkyl, alkenyl, aryl, and aralkyl.