O-methylated rapamycin derivatives for alleviation and inhibition of lymphoproliferative disorders

摘要

The present invention relates to methods of alleviating and inhibiting a lymphoproliferative disorder in a mammal, the method comprising administering one or more rapamycin derivatives (including rapamycin) to the mammal. Further, the invention provides a method for identifying agents which are useful for alleviating and inhibiting a lymphoproliferative disorders, as well as a method for identifying agents which are capable of inhibiting metastasis of lymphatic tumors in a mammal.

主权项

1. A method of alleviating a lymphoproliferative disorder in a human patient, the method comprising administering to the patient, in an amount sufficient to alleviate the disorder, a rapamycin derivative having the chemical structure wherein
X is (H, H) or O;Y is (H, OH) or O;R1 is 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; andeither R4 is methyl or R4 and R1 together form a C2-5 alkylene moiety, wherein the lymphoproliferative disorder is a B-cell lymphoma.