Substituted camptothecin derivatives and process for their preparation

A camptothecin compound represented by formula (I):

• ##STR77## wherein the symbol - - - - represents a double bond;
• R.sub.1, R.sub.2 and R.sub.3 are as defined under (a) or (b) below:
• (a) R.sub.1 and R.sub.2 are each, independently,
• hydrogen;
• C.sub.1 -C.sub.4 alkyl;
• C.sub.3 -C.sub.7 cycloalkyl;
• phenyl C.sub.1 -C.sub.6 alkyl;
• a phenyl group, wherein said phenyl group is optionally substituted with one member selected from the group consisting of C.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.6 alkoxy, C.sub.1 -C.sub.6 alkanoyloxy, nitro and halogen;
• --NR.sub.5 R.sub.6, wherein one of R.sub.5 and R.sub.6 is hydrogen, C.sub.1 -C.sub.6 alkyl or benzyl and the other is hydrogen, C.sub.1 -C.sub.6 alkanoyl, C.sub.1 -C.sub.6 alkoxycarbonyl, trichloroethoxycarbonyl, benzoyl, wherein the phenyl ring of said benzoyl is optionally substituted with one member selected from the group consisting of C.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.6 alkoxy, C.sub.1 -C.sub.6 alkanoyloxy, nitro and halogen, phenyl C.sub.1 -C.sub.6 alkanoyl, phenoxycarbonyl, wherein the phenyl ring of said phenoxycarbonyl is optionally substituted with one member selected from the group consisting of C.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.6 alkoxy, C.sub.1 -C.sub.6 alkanoyloxy, nitro and halogen, or phenyl C.sub.1 -C.sub.6 alkoxycarbonyl,
• or R.sub.5 and R.sub.6, combined together with the nitrogen atom to which they are linked, form a 4-6 membered saturated heteromonocyclic ring represented by the formula (G):
• ##STR78## wherein W is --C.dbd.O, R.sub.7 is hydrogen or C.sub.1 -C.sub.6 alkyl and n is an integer of 2 to 4;
• --COOR.sub.8 wherein R.sub.3 is hydrogen, C.sub.1 -C.sub.6 alkyl, C.sub.3 -C.sub.7 cycloalkyl or phenyl C.sub.1 -C.sub.6 alkyl;
• or
• --COR.sub.9, wherein R.sub.9 is C.sub.1 -C.sub.6 alkyl, C.sub.3 -C.sub.7 cycloalkyl, phenyl C.sub.1 -C.sub.6 alkyl, or phenyl, wherein said phenyl is optionally substituted with one member selected from the group consisting of C.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.6 alkoxy, C.sub.1 -C.sub.6 alkanoyloxy, nitro and halogen, or NR.sub.10 R.sub.11 wherein R.sub.10 and R.sub.11 are each, independently, hydrogen or C.sub.1 -C.sub.6 alkyl;
• and
• R.sub.3 is hydrogen, C.sub.1 -C.sub.6 alkyl or a phenyl group, wherein said phenyl group is optionally substituted with one member selected from the group consisting of C.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.6 alkoxy, C.sub.1 -C.sub.6 alkanoyloxy, nitro and halogen;
• or
• (b) R.sub.1 and R.sub.3, combined together, form a 5-8 membered carbomonocyclic ring;
• and
• R.sub.2 is hydrogen, C.sub.1 -C.sub.4 alkyl or C.sub.3 -C.sub.7 cycloalkyl;
• R.sub.4 is hydrogen, C.sub.1 -C.sub.6 alkyl, or phenyl C.sub.1 -C.sub.6 alkyl;
• X is hydrogen, C.sub.1 -C.sub.6 alkyl, C.sub.3 -C.sub.7 cycloalkyl, C.sub.1 -C.sub.6 alkoxy, C.sub.3 -C.sub.7 cycloalkoxy, C.sub.1 -C.sub.6 alkanoyloxy, benzoyloxy, amino, hydroxy, or nitro, or a pharmaceutically acceptable salt thereof,
• with the proviso that R.sup.1, R.sup.2 and R.sup.3 are each simultaneously not a tert-butyl group or a substituted or unsubstituted phenyl group.