MACROCYCLIC LACTONES, COMPOSITIONS, AND METHODS OF USE

摘要

The present invention provides compound of the formula:wherein R1 and R2 are the same or different and are independently H, C1-C6 straight-chain or branched saturated or unsaturated alkyl, aryl, R6CH2-, R6CO-, or R6SO2-, wherein R6 is H, C1-C6 straight-chain or branched saturated or unsaturated alkyl, or aryl; R3 is H, C1->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 OR1 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.