ANTITUMORAL ECTEINASCIDIN DERIVATIVES

摘要

This invention relates to compounds of the formula: ##STR00001## wherein: the substituent groups defined by R.sub.1, R.sub.2 are each independently selected of H, C(.dbd.O)R', C.sub.1 C.sub.18 alkyl, C.sub.2 C.sub.18 alkenyl, C.sub.2 C.sub.18 alkynyl, or aryl; each of the R' groups is independently selected from the group consisting of H; OH; NO.sub.2; NH.sub.2; SH; CN; halogen; .dbd.O; C(.dbd.O)H; C(.dbd.O)CH.sub.3; CO.sub.2H; or C.sub.1 C.sub.18 alkyl, C.sub.2 C.sub.18 alkenyl, C.sub.2 C.sub.18 alkynyl, or aryl, each of which, independently, may be substituted with one or more substituents selected from the group consisting of halogen, cyano, hydroxy, nitro, azido; alkanoyl, carboxamido, alkyl, alkenyl, alkynyl, aryloxy, alkoxy, alkylthio, alkylsulfinyl, alkylsulfonyl, aminoalkyl, carbocylic aryl having 6 or more carbons, and aralkyl; X.sub.2 is OX.sub.1 or N(X.sub.1).sub.2 wherein each X.sub.1 is independently H, C(.dbd.O)R' where R' is as defined, C.sub.1 C.sub.18 alkyl, C.sub.2 C.sub.18 alkenyl, C.sub.2 C.sub.18 alkynyl, aryl, alkoxy, heterocyclyl, or two X.sub.1 groups together form a cyclic substituent on the nitrogen atom, or X.sub.1 is SO.sub.2CH.sub.3 when X.sub.2 is OX.sub.1, or N(X.sub.1).sub.2 is NHCOalkylCOOH, NHBiotin, NH(aa).sub.y where aa is amino acid acyl and Y is 1, 2 or 3 optionally with a amide terminal group, protected NHCOCH(NH.sub.2)CH.sub.2SH, NHCOalkenylaryl substituted with CF.sub.3, or m-methoxycarbonylbenzoylNH; wherein N(X.sub.1).sub.2 is not NH.sub.2; X.sub.3 is selected of OR.sub.1 where R.sub.1 is as defined, CN, (.dbd.O), or H; X.sub.4 is--H or C.sub.1 C.sub.18 alkyl; and X.sub.5 is selected of H, or R.sub.1 where R.sub.1 is as defined; provided that the compound is not ecteinascidin 583 or 597, which are useful for treating tumors.