公开(公告)号：EP1000053B1

公开(公告)日：2004-06-30

申请号：EP98935844.5

申请日：1998-07-23

申请人： THE GOVERNMENT OF THE UNITED STATES OF AMERICA, as represented by THE SECRETARY, DEPARTMENT OF HEALTH AND HUMAN SERVICES

发明人： BOYD, Michael, R. ,  MCKEE, Tawnya, C. ,  CARDELLINA, John, H., II ,  BEUTLER, John, A. ,  ERICKSON, Karen ,  GALINIS, Deborah ,  PANNELL, Lewis

IPC分类号： C07D313/00 ,  C07D321/00 ,  A61K31/365

CPC分类号： C07D321/00 ,  C07D313/00

摘要： The present invention provides a compound of formula (I), wherein R?1 and R2¿ are the same or different and are independently H, C¿1?-C6 straight-chain or branched-chain saturated or unsaturated alkyl, aryl, R?6CH¿2-, R6CO-, or R6SO2-, wherein R6 is H, C¿1?-C6 straight-chain or branched-chain saturated or unsaturated alkyl, or aryl; R?3¿ is H, C¿1?-C6 straight-chain or branched-chain saturated alkyl, aryl, an oxime, or an oxime methyl ether; at least one aromatic ring position is optionally substituted with a substituent selected from the group consisting of halo, nitro, amino, hydroxyl, thio, acyl, C1-C6 alkyl, and cyano; and Z is a contiguous linker comprising a chain of 7-10 atoms (including heteroatoms) which atoms, together with the five atoms beginning with the carbon of the aromatic ring in meta-relationship with OR?1¿ and ending with the carbon directly attached to the alkyl oxygen of the lactone, which carbons are covalently bonded to either end of linker Z, integrally form a 12-15 membered ring; or a pharmaceutically acceptable salt, an ester, or a prodrug thereof. The present invention further provides a pharmaceutical composition, and a method of preventing or treating cancer, using at least one compound of the present invention, optionally in conjunction with an additional compound other than a compound of the present invention.