发明名称 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.
申请公布号 US8778961(B2) 申请公布日期 2014.07.15
申请号 US201012830883 申请日期 2010.07.06
申请人 The Trustees of the University of Pennsylvania 发明人 Wasik Mariusz A.;Shaw Leslie M.
分类号 A61K31/44;A61K31/535 主分类号 A61K31/44
代理机构 Saul Ewing, LLP 代理人 Saul Ewing, LLP ;Doyle Kathryn
主权项 1. 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)3Si;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)3Si;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, thereby inhibiting development of a disorder characterized by proliferation of lymphocytes infected with an EBV in the patient.
地址 Philadelphia PA US