Methods for Attenuating Graft-Versus-Host Disease and Opportunistic Infections

A method for decreasing the risk of developing graft versus host disease following transplantation of a graft comprising hematopoietic stem cells in a subject in need thereof, comprising contacting the graft with an effective amount of a compound of Formula I or Formula II or a pharmaceutically acceptable salt or prodrug thereof:

• wherein
• R1 to R11 and R11′ are independently H, halogen, hydroxy, amino, C1-C5 alkoxy, benzoyloxy, R14C(O)O, COOH or a salt thereof, SO3H or a salt thereof, PO3H2 or a salt thereof, C1-C24 alkyl, COOR15, SO3R16, C(O)NR17R18, SO2NR19R20, SR21, SCH2R25, SC(O)R21, NR22R23, NHC(O)—R24, O(CH2)n—R26—R27, OC(O)N(H)C(H)(R28)COOR29;
• R12 and R13 are C1-C7 alkyl groups;
• R14 is H or C1-C5 alkyl;
• R15 is aryl or C1-C5 alkyl;
• R16 is aryl or C1-C5 alkyl;
• R17 and R18 are each independently H, C1-C5 alkyl, aryl or hydroxy;
• R19 and R20 are each independently H, C1-C5 alkyl or aryl;
• R21 is C1-C5 alkyl or aryl;
• R22 and R23 are each independently H, C1-C5 alkyl or aryl;
• R24 is aryl optionally substituted with COOH or a salt thereof, or C1-C7 alkoxy;
• R25 is aryl;
• R26 is aryl;
• R27 is COOH or a salt thereof, B(OH)2 or a salt thereof, nitro, C1-C7 alkoxy or aryl, wherein the aryl is substituted with COOH or a salt thereof, B(OH)2 or a salt thereof, nitro or C1-C7 alkoxy;
• R28 is an amino acid side chain;
• R29 is H or a C1-C4 alkyl;
• X is a (C1-C7 alkylene) or (C1-C7 alkylene)C(O)NH;
• and
• n is 1 to 7;
• and
• transplanting the contacted graft into the subject;
• thereby decreasing the developing risk of graft versus host disease.

A method for decreasing the risk of microbial infection after transplantation of a graft comprising hematopoietic stem cells in a subject in need thereof, comprising administering to the subject an effective amount of a compound of Formula I or Formula II or a pharmaceutically acceptable salt or prodrug thereof:

• wherein
• R1 to R11 and R11′ are independently H, halogen, hydroxy, amino, C1-C5 alkoxy, benzoyloxy, R14C(O)O, COOH or a salt thereof, SO3H or a salt thereof, PO3H2 or a salt thereof, C1-C24 alkyl, COOR15, SO3R16, C(O)NR17R18, SO2NR19R20, SR21, SCH2R25, SC(O)R21, NR22R23, NHC(O)—R24, O(CH2)n—R26—R27, OC(O)N(H)C(H)(R28)COOR29;
• R12 and R13 are C1-C7 alkyl groups;
• R14 is H or C1-C5 alkyl;
• R15 is aryl or C1-C5 alkyl;
• R16 is aryl or C1-C5 alkyl;
• R17 and R18 are each independently H, C1-C5 alkyl, aryl or hydroxy;
• R19 and R20 are each independently H, C1-C5 alkyl or aryl;
• R21 is C1-C5 alkyl or aryl;
• R22 and R23 are each independently H, C1-C5 alkyl or aryl;
• R24 is aryl optionally substituted with COOH or a salt thereof, or C1-C7 alkoxy;
• R25 is aryl;
• R26 is aryl;
• R27 is COOH or a salt thereof, B(OH)2 or a salt thereof, nitro, C1-C7 alkoxy or aryl, wherein the aryl is substituted with COOH or a salt thereof, B(OH)2 or a salt thereof, nitro or C1-C7 alkoxy;
• R28 is an amino acid side chain;
• R29 is H or a C1-C4 alkyl;
• X is a (C1-C7 alkylene) or (C1-C7 alkylene)C(O)NH;
• and
• n is 1 to 7;
• thereby decreasing the risk of microbial infection.