Induction of immune tolerance

A composition comprising an immunsuppressive agent and a compound represented by the following structural formula:

• 9
• or a physiological salt thereof, wherein:
• R1 is a substituted or unsubstituted aryl group or a substituted or unsubstituted alkyl group;
• R2 is an optionally substituted aralkyl group or an alkyl group substituted with —NR5R6;
• R3 is a substituted or unsubstituted alkyl group or a substituted or unsubstituted aryl group;
• R4 a substituted or unsubstituted alkyl group or a substituted or unsubstituted aryl group;
• and
• R5 and R6 are independently selected from a substituted or unsubstituted alkyl group or a substituted or unsubstituted aryl group or R5 and R6 taken together with the nitrogen to which they are attached are a non-aromatic heterocyclic group.

A composition comprising an anti CD40L monoclonal antibody or repamycin and a compound represented by the following structural formula:

• 10
• or a pharmaceutically acceptable salt of the compound.
• 11
• R11 is —H, a substituted or unsubstituted aryl, a substituted or unsubstituted aralkyl, a substituted or unsubstituted heteroaryl or a substituted or unsubstituted heteroaralkyl;
• R12 is alkyl substituted with NR15R16, a substituted or unsubstituted aryl, a substituted or unsubstituted heteroaralkyl, or a substituted or unsubstituted heterocycloalkylalkyl;
• R13 is a substituted or unsubstituted alkyl, a substituted or unsubstituted aryl, a substituted or unsubstituted aralkyl, a substituted or unsubstituted cycloalkylalkyl, a substituted or unsubstituted heteroaryl, a substituted or unsubstituted heteroaralkyl, a substituted or unsubstituted benzophenonyl, or a substituted or unsubstituted cycloalkylalkyl;
• and
• each R14 is independently, —H, a substituted or unsubstituted alkyl, a substituted or unsubstituted aryl, substituted or unsubstituted aralkyl or a substituted or unsubstituted heteroaralkyl;
• R15 and R16 are independently selected from H, a substituted or unsubstituted alkyl, a substituted or unsubstituted cycloalkyl, a substituted or unsubstituted aryl or unsubstituted aralkyl or R15 and R16 together with the nitrogen to which they are attached are a heterocycloalkyl.

A method of inhibiting rejection of a transplanted organ, tissue or cell in a mammal, the method comprising the step of administering to the recipient mammal an effective amount of an immunosuppressive agent and an effective amount of a compound represented by the following structural formula:

• 12
• R11 is —H, a substituted or unsubstituted aryl, a substituted or unsubstituted aralkyl, a substituted or unsubstituted heteroaryl or a substituted or unsubstituted heteroaralkyl;
• R12 is alkyl substituted with NR15R16, a substituted or unsubstituted aryl, a substituted or unsubstituted heteroaralkyl, or a substituted or unsubstituted heterocycloalkylalkyl;
• R13 is a substituted or unsubstituted alkyl, a substituted or unsubstituted aryl, a substituted or unsubstituted aralkyl, a substituted or unsubstituted cycloalkylalkyl, a substituted or unsubstituted heteroaryl, a substituted or unsubstituted heteroaralkyl, a substituted or unsubstituted benzophenonyl, or a substituted or unsubstituted cycloalkylalkyl;
• and
• each R14 is independently, —H, a substituted or unsubstituted alkyl, a substituted or unsubstituted aryl, substituted or unsubstituted aralkyl or a substituted or unsubstituted heteroaralkyl;
• R15 and R16 are independently selected from H, a substituted or unsubstituted alkyl, a substituted or unsubstituted cycloalkyl, a substituted or unsubstituted aryl or unsubstituted aralkyl or R15 and R16 together with the nitrogen to which they are attached are a heterocycloalkyl.