| 摘要 |
Fused heterocyclo 4,8-ethano isoindole carboxylic acid derivatives (I), their isomers and salts are new. Compounds of formula (I) are new. Het = a mono-, bi-, or tri-cyclic fused system in which each ring is 4-7 membered, at least one of the rings contains at least one 1-4 O, N or S, optionally substituted, the heterocyclic being fused to the isoindole system by of its two adjacent atoms; Ar = phenyl (optionally substituted by one or more halo, alkyl, perhaloalkyl, alkenyl, OH, SH, alkylthio, CN, alkoxy, and perhaloalkoxy), phenyl (fused to a 4-7 membered heterocycle with one or more O, N or S), aromatic or non-aromatic polycycle, aromatic or non-aromatic 5-12 membered heterocycle having one or more O, N or S linked to the fused ring via a C-C bond and optionally substituted by one or more halo, alkyl, alkenyl, OH, alkoxy, SH, alkylthio, CN or CF3; R = -CO-Z; Z = OH, OR4 or -N(R5)(R6); R4 = alkyl; R5 = H or alkyl; R6 = H, OH, alkyl (optionally substituted by amino, alkylamino, dialkylamino, OH, alkoxy, SH, alkylthio, alkoxycarbonyl, CN, aromatic mono- or 5-12 membered polycycle optionally containing one or more hetero atoms and optionally substituted or phenyl optionally substituted one or more halo, CF3, alkyl, alkenyl, alkoxy, alkylthio, alkylamino, or 1- or 2-naphthyl), or amino (optionally substituted by one or two alkyl, aryl (optionally substituted by one or more alkyl or alkoxy), 5-7 membered heterocycle containing one or more N,O or S, optionally substituted arylcarbonyl, or alkoxy optionally substituted by phenyl); R1, R2 = H, halo, alkyl or alkoxy (all optionally substituted by dialkylamino, alkylthio or alkoxycarbonyl); R3 = H, alkyl or alkylthio; X = methylene, alken-1,1-diyl or cycloalkan-1,1-diyl containing 3-6C. Independent claims are included for: (a) intermediates of formulae (III) and (VI); and (b) the preparations of (I) intermediates (III) and (VI); and (c) the combination of (I) with one or more pharmacologically active compounds and/ora radiotherapy, in order to achieve a synergistic effect. G1 = H or amino protecting group such as as benzyl; G1' = benzyl.
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