Camptothecin derivatives, preparations thereof and antitumor agents

New camptothecin derivatives of the general formula (1): ##STR1## wherein R.sup.1 represents a hydrogen atom or a C.sub.1 -C.sub.6 alkyl group, R.sup.2 represents a hydrogen or a C.sub.1 -C.sub.6 alkoxy group, R.sup.3 represents a hydrogen or halogen atom or a C.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.6 alkoxy, hydroxyl, C.sub.2 -C.sub.6 acyloxy or methoxyethoxymethoxy group, R.sup.4 represents a hydrogen or halogen atom, and R.sup.5 represents a C.sub.1 -C.sub.6 alkyl, C.sub.3 -C.sub.6 unsaturated alkyl, alkylthioalkyl, alkoxyalkyl, pyridyl or substituted phenyl group, with the proviso that all of the R.sup.2, R.sup.3 and R.sup.4 substituents should not be a hydrogen atom, and a process for preparing the new camptothecin derivatives by subjecting the camptothecin derivatives of the general formula (2): ##STR2## wherein R.sup.1, R.sup.2, R.sup.3 and R.sup.4 have the same meanings as given above, to the reaction with N,N-dimethylethylenediamine without solvent to open the E-lactone ring followed by acylation of 17-hydroxyl group with corresponding acylating agents and an antitumor agent containing the same as an active ingredient.

BACKGROUND OF THE INVENTION 
1. Field of the Invention 
The present invention relates to new water-soluble camptothecin 
derivatives, a process of the preparation thereof and antitumor agents 
containing the same as an active ingredient. 
2. Description of the Prior Art 
The present inventors have made an exploratory research and provided a 
number of new camptothecin (hereinafter referred to CPT) derivatives with 
excellent antitumor activities, and found that totally synthetic CPT 
derivatives carrying a lower alkyl group in 7-position on the B-ring and 
also hetero substituent and/or alkyl group in 9-, 10- and 11-position on 
the A-ring among others showed strong antitumor activity (see JP, A, 
H1-186892). 
The present inventors have also made extensive researches to make the 
derivatives water-soluble by various means in order to solve a problem in 
case of administration. Especially, CPT derivatives synthesized by 
subjecting 7-ethylCPT to open the E-lactone ring by the diamines followed 
by acylation of the hydroxymethyl group showed excellent water solubility 
without decrease of antitumor activity contrasting to the known E-ring 
opened water soluble CPT derivatives (see JP, A, H1-131179 or U.S. Pat. 
No. 4,914,205). 
In addtion to further research to obtain other new CPT derivatives with 
more excellent antitumor activity and with useful water solubility in case 
of administration, there is also a great demand in the art for creating 
new CPT derivatives which solve both toxicity and usage problems. 
BRIEF SUMMARY OF THE INVENTION 
Accordingly, an object of this invention is to provide new CPT derivatives 
possessing excellent characteristics in an antitumor activity. It is 
another object to provide new CPT derivatives which solve water solubility 
problem. In order to achieve those objects, we provided a process for the 
preparation of new water-soluble CPT derivatives prepared from CPT 
derivatives carrying a lower alkyl group in 7-position on the B-ring and 
also hetero substituent and/or alkyl group in 9-, 10- and 11-position on 
the A-ring by subjecting them to open the E-lactone ring by the diamines 
followed by acylation of the hydroxymethyl group. As a result of our 
extensive safety and galenical researches made for these new water-soluble 
CPT derivatives, it has been realized to achieve the above mentioned 
objects, and we succeeded in providing excellent new CPT derivatives as an 
antitumor agent in the invention.