Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Carbohydrate doai
Patent
1996-11-08
1998-09-08
Shah, Mukund J.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Carbohydrate doai
514 43, 536 177, 536 187, 536 271, 536 291, A61K 3170, C07H 1702
Patent
active
058045643
DESCRIPTION:
BRIEF SUMMARY
TECHNICAL FIELD
This invention relates to novel indolopyrrolocarbazole derivatives which are useful in the field of medicine and, more specifically, inhibit the growth of tumor cells and thereby exhibit an antitumor effect, their intermediates, processes for preparing them, and their use.
BACKGROUND ART
In the field of cancer chemotherapy, a large number of compounds have already been put to practical use as antitumor agents. However, their activities against various types of tumors are not necessarily satisfactory, and the problem of tolerance of tumor cells to these Proceedings of the 47th General Meeting of the Japan Cancer Society, pp. 12-15 (1988)!.
Under these circumstances, the development of novel cancerocidal substances are invariably desired in the field of cancer therapy. Among others, there is a need for substances which overcome the problem of tolerance to the existing cancerocidal substances and exhibit effectiveness against such types of cancers as cannot be effectively controlled by the existing cancerocidal substances.
In view of the above-described state of the art, the present inventors screened a wide variety of microbial metabolites, found a novel compound BE-13793C having antitumor activity and the Journal of Antibiotics, Vol. 44, pp. 723-728 (1991)!.
Thereafter, they created an indolopyrrolocarbazole compound having excellent antitumor activity by a chemical modification of BE-13793C, and disclosed it (see International Publication No. W091/18003 and European Patent Laid-Open No. EP0545195 A1).
A problem to be solved by the present invention is to create a compound having more excellent antitumor activity than the indolopyrrolocarbazole-derived antitumor substances disclosed in the prior patent application (International Publication No. W091/18003 and European Patent Laid-Open No. EP0545195 A1).
DISCLOSURE OF THE INVENTION
The present inventors have synthesized a large number of indolopyrrolocarbazole derivatives and have examined their antitumor activities, with a view to creating a compound having more excellent antitumor activity than the indolopyrrolocarbazole-derived antitumor compounds which were previously disclosed. As a result, it has now been are novel compounds having very excellent antitumor activity, stability and safety.
Thus, the present invention relates to the compounds of the general formula ##STR2## wherein R.sup.1 and R.sup.2 each represent an OH group, R.sup.1 is located at the 1- or 2-position, R.sup.2 is located at the 10- or 11-position, R.sup.2 is located at the 11-position when R.sup.1 is located at the 1-position, and R.sup.2 is located at the 10-position when R.sup.1 is located at the 2-position, or pharmaceutically acceptable salts thereof, their intermediates, processes for preparing them, and their use.
The compounds of the present invention and their intermediates can be prepared according to the processes represented by the following procedures A to E. ##STR3##
The definitions of the symbols and terms used in procedures A to E and the claims given later are as follows.
In the general formulas, R.sup.1 and R.sup.2 each represent an OH group, provided that R.sup.1 is located at the 1- or 2-position on the ring, R.sup.2 is located at the 10- or 11-position on the ring, R.sup.2 is located at the 11-position when R.sup.1 is located at the 1-position, and R.sup.2 is located at the 10-position when R.sup.1 is located at the 2-position.
R.sup.3 represents a lower alkyl group, a benzyloxymethyl group or an aralkyl group. The term "lower alkyl group" means straight-chain or branched alkyl groups of 1 to 6 carbon atoms, such as methyl, ethyl, propyl, sec-propyl, butyl, pentyl and hexyl. The term "aralkyl group" means aralkyl groups of 7 to 12 carbon atoms, such as benzyl, phenethyl and phenyl propyl.
R.sup.4 represents a hydrogen atom, a lower alkyl group, a benzyloxymethyl group or an aralkyl group. The terms "lower alkyl group" and "aralkyl group" have the same meanings as described for R.sup.3.
R.sup.5 and R.sup.6 each represent a protected OH group, p
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Arakawa Hiroharu
Kojiri Katsuhisa
Kondo Hisao
Ohkubo Mitsuru
Suda Hiroyuki
Banyu Pharmaceutical Co. Ltd.
Rao Deepak R.
Shah Mukund J.
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