O-Methylated Rapamycin Derivatives For Alleviation And Inhibition Of Lymphoproliferative Disorders

A method of inhibiting a lymphoproliferative disorder characterized by a proliferation of lymphocytes that have been infected with an Epstein-Barr

• virus (EBV) in a human patient at risk for developing the disorder due to presence of lymphocytes infected with Epstein Barr virus (EBV), the method comprising administering to the patient after detection of EBV-infected lymphocytes, and in an amount sufficient to inhibit the disorder, a rapamycin derivative having the chemical structure
• wherein
• X is (H, H) or O;
• Y is (H, OH) or O;
• R1 is independently selected from the group consisting of alkyl, thioalkyl, arylalkyl, hydroxyalkyl, dihydroxyalkyl, hydroxyalkylarylalkyl, dihydroxyalkylarylalkyl, alkoxyalkyl, acyloxyalkyl, aminoalkyl, alkylaminoalkyl, alkoxycarbonylaminoalkyl, acylaminoalkyl, arylsulfonamidoalkyl, allyl, dihydroxyalkylallyl, dioxolanylallyl, carbalkoxyalkyl, and (R3)3 Si;
• R2 is selected from the group consisting of —H, alkyl, thioalkyl, arylalkyl, hydroxyalkyl, dihydroxyalkyl, hydroxyalkylarylalkyl, dihydroxyalkylarylalkyl, alkoxyalkyl, acyloxyalkyl, aminoalkyl, alkylaminoalkyl, alkoxycarbonylaminoalkyl, acylaminoalkyl, arylsulfonamidoalkyl, allyl, dihydroxyalkylallyl, dioxolanylallyl, carbalkoxyalkyl, and (R3)3 Si;
• each R3 is independently selected from the group consisting of —H, methyl, ethyl, isopropyl, tert-butyl, and phenyl;
• and
• either R4 is methyl or R4 and R1 together form a C2-5 alkylene moiety, thereby inhibiting development of a disorder characterized by proliferation of lymphocytes infected with an EBV in the patient.