Camptothecin is a kind of a plant alkaloid contained in "Kiju" (Camptotheca acuminate Decne.) native to China, and the like. Although the development thereof was advanced as an antitumor agent, it was suspended due to toxicity thereof such as strong inhibition of bone marrow. Thereafter, the camptothecin was used as a starting material and subjected to various chemical modifications to synthesize a compound represented by the following formula I and having a high antitumor activity and a wide range of an antitumor spectrum (see Japanese Examined Patent Publication (Kokoku) No. 3-4077). ##STR2##
However, the compound represented by the formula I was found to cause diarrhea as an adverse effect when it was clinically applied. The substance causative of the diarrhea has been estimated to be a compound (7-ethyl-10-hydroxycamptothecin) represented by the following formula III ##STR3## which is produced when a glucuronic acid inclusion compound (7-ethylcamptothecin-10-yl .beta.-D-glucopyranosidouronic acid) which is a main metabolite of the compound represented by the formula I and represented by the formula II ##STR4## is subjected to the action of .beta.-glucuronidase in an alimentary canal.
For this reason, it is expected that the prevention of the elimination of glucuronic acid through the inhibition of the enzymatic activity of .beta.-glucuronidase in the alimentary canal enables the formation of the compound represented by the formula III to be prevented, so that the occurrence of diarrhea can be suppressed.
USPTO Backgrounds
USPTO Backgrounds