BORNEOL DERIVATIVES AFFECTING TUBULIN POLYMERIZATION AND DEPOLYMERIZATION

摘要

PCT No. PCT/EP95/01341 Sec. 371 Date Jan. 3, 1997 Sec. 102(e) Date Jan. 3, 1997 PCT Filed Apr. 13, 1995 PCT Pub. No. WO95/30650 PCT Pub. Date Nov. 16, 1995The invention relates to borneol derivatives of general formula I I in which R1 means C(O)-CH(OR6)-CH(NHR7)-R8, R2 means hydrogen, -OH, C1-C10 alkyl, C1-C10 alkoxy, -OC(O)R9a, -OSO2R9a, -OP(O)(OH)2, NHR9a, NR9aR9b, R3 means hydrogen, -OH, C1-C10 alkoxy, -OC(O)R9b, -OSO2R9b, -OP(O)(OH)2, or R2, R3 together mean an oxygen atom, R4 means hydrogen, C1-C10 alkyl, -(CH2)n-OR11a, R5 means hydrogen, C1-C10 alkyl, -(CH2)p-OR11b, or R4, R5 together mean an oxygen atom, a=CHR10 group, n means 0 to 8, p means 1 to 8, R7 means -C(O)R12, -SO2R12, -C(O)OR12, -C(O)NHR9d, -C(O)NR9dR9e, R8 means aryl, R9a-e, R12 are the same or different and mean C1-C10 alkyl, C4-C8 cycloalkyl, aryl, C7-C16 aralkyl, R10 means hydrogen, C1-C10 alkyl, -(CH2)s-OR14, s means 1 to 8, R6, R11a,b, R14 are the same or different and mean hydrogen, C1-C10 alkyl, aryl, C7-C16 aralkyl, -SO2R9c, -P(O)(OH)2, R13, R15a,b are the same or different and mean hydrogen, C1-C10 alkyl, aryl, C7-C16 aralkyl, X1, X2 are the same or different and mean X, X can be hydrogen, halogen, -OH, -NO2, -N3, -CN, -NR15aR15b, -NHSO2R15a, -CO2R15, C1-C10 alkyl, C1-C10 alkoxy, C1-C10 acyloxy, C1-C10 acyl, and, if R15 means hydrogen, their salts with physiologically compatible bases, as well as the alpha -, beta -or gamma -cyclodextrin clathrates, as well as the compounds of formula I that are encapsulated with liposomes.