This invention relates to novel derivatives of camptothecin, and will, particularly to derivatives having a substitution at the C-7 position, or at one of the C-9, C-10, C-11 or C-12 positions, or to disubstituted derivatives having a first substitution at C-7 and a second at one of C-9, C-10, C-11 or C-12. The invention also includes methods of using the compounds as Topoisomerase I inhibitors to treat patients with cancer. The invention also includes pharmaceutical formulations which consist of the novel compounds in solution or suspension with one or more pharmaceutical excipients or dilutes.
The present invention provides generally a compound having the following general formula (1): ##STR00001## wherein R.sup.1 and R.sup.2 are independently the same or different and are hydrogen, an alkyl group, an alkenyl group, a benzyl group, an alkynyl group, an alkoxyl group, an aryloxy group, an acyloxy group, a carbonyloxy group, a carbamoyloxy group, a halogen, a hydroxyl group, a nitro group, a cyano group, an azido group, a formyl group, a hydrazino group, an acyl group, an amino group, --SR.sup.c, wherein, R.sup.c is hydrogen, an acyl group, an alkyl group, or an aryl group, or R.sup.1 and R.sup.2 together form a group of the formula --O(CH.sub.2).sub.nO-- wherein n represents the integer 1 or 2; R.sup.3 is H, F, a halogen atom, a nitro group, an amino group, a hydroxyl group, or a cyano group; or R.sup.2 and R.sup.3 together form a group of the formula --O(CH.sub.2).sub.nO-- wherein n represents the integer 1 or 2; R.sup.4 is H, F, a C.sub.1-3 alkyl group, a C.sub.2-3 alkenyl group, a C.sub.2-3 alkynyl group, or a C.sub.1-3 alkoxyl group; R.sup.5 is a C.sub.1-10 alkyl group, or a propargyl group; and R.sup.6, R.sup.7 and R.sup.8 are independently a C.sub.1-10 alkyl group, a C.sub.2-10 alkenyl group, a C.sub.2-10 alkynyl group, an aryl group or a --(CH.sub.2).sub.NR.sup.9 group, wherein N is an integer within the range of 1 through 10 and R.sup.9 is a hydroxyl group, alkoxy group, an amino group, an alkylamino group, a dialkylamino group, a halogen atom, a cyano group or a nitro group; and pharmaceutically acceptable salts thereof.
The present invention provides generally a compound having the following general formula (1): ##STR00001## wherein R.sup.1 and R.sup.2 are independently the same or different and are hydrogen, an alkyl group, an alkenyl group, a benzyl group, an alkynyl group, an alkoxyl group, an aryloxy group, an acyloxy group, a carbonyloxy group, a carbamoyloxy group, a halogen, a hydroxyl group, a nitro group, a cyano group, an azido group, a formyl group, a hydrazino group, an acyl group, an amino group, --SR.sup.c, wherein, R.sup.c is hydrogen, an acyl group, an alkyl group, or an aryl group, or R.sup.1 and R.sup.2 together form a group of the formula --O(CH.sub.2).sub.nO-- wherein n represents the integer 1 or 2; R.sup.3 is H, F, a halogen atom, a nitro group, an amino group, a hydroxyl group, or a cyano group; or R.sup.2 and R.sup.3 together form a group of the formula --O(CH.sub.2).sub.nO-- wherein n represents the integer 1 or 2; R.sup.4 is H, F, a C.sub.1-3 alkyl group, a C.sub.2-3 alkenyl group, a C.sub.2-3 alkynyl group, or a C.sub.1-3 alkoxyl group; R.sup.5 is a C.sub.1-10 alkyl group, or a propargyl group; and R.sup.6, R.sup.7 and R.sup.8 are independently a C.sub.1-10 alkyl group, a C.sub.2-10 alkenyl group, a C.sub.2-10 alkynyl group, an aryl group or a --(CH.sub.2).sub.NR.sup.9 group, wherein N is an integer within the range of 1 through 10 and R.sup.9 is a hydroxyl group, alkoxy group, an amino group, an alkylamino group, a dialkylamino group, a halogen atom, a cyano group or a nitro group; and pharmaceutically acceptable salts thereof.
