Indolo[2,3-b]quinoxaline derivatives

Details Indolo[2,3-b]quinoxaline derivatives Indolo[2,3-b]quinoxaline derivatives

1995-10-16

1997-01-28

Grumbling, Matthew V.

Organic compounds -- part of the class 532-570 series

Organic compounds

Nitrogen attached directly or indirectly to the purine ring...

C07D24136

Patent

active

055979211

DESCRIPTION:

BRIEF SUMMARY
This is a national stage application, filed under 37 C.F.R. 1.371 of PCT/JP94/00673, filed Apr. 22, 1994 and published as WO94/24135 Oct. 27, 1994.


TECHNICAL FIELD

The present invention relates to indolo[2,3-b]quinoxaline derivatives, and more particularly to novel indolo[2,3-b]quinoxaline derivatives and pharmaceutically acceptable salts having an antitumor activity.


BACKGROUND ART

Among known compounds having an indolo[2,3-b]quinoxaline ring with an antitumor activity are two kinds of the compounds reported in Japanese Patent Laid-open No. 63-502587 and ibid. 63-502588.
However, the antitumor effect of these compounds is insufficient.
Accordingly, an object of the present invention is to provide novel indolo[2,3-b]quinoxaline derivatives having an excellent antitumor activity.


DISCLOSURE OF THE INVENTION

An object of the present invention is to provide indolo[2,3-b]quinoxaline derivatives represented by Formula (I): ##STR2## wherein
one of R.sup.1 and R.sup.2 is a hydrogen atom and the other is a group represented by Formula (II): ##STR3## wherein R.sup.4 is a hydrogen atom or a methyl group, R.sup.5, R.sup.6 and R.sup.7 are the same or different, and are each a hydrogen atom, a straight or branched lower alkyl group or a group represented by Formula (III): an acetyl group; and
R.sup.3 is a hydrogen atom, a methyl group or a group represented by Formula (IV): and Q is a hydrogen atom, a hydroxyl group, a methoxy group, an ethoxy group, an acetoxy group or an acetamido group;


BEST MODE FOR CARRYING OUT THE INVENTION

In the definitions of Formula (I), the straight or branched lower alkyl group for R.sup.5, R.sup.6, R.sup.7 or X refers to a C.sub.1 -C.sub.6 lower alkyl group such as, for example, a methyl group, an ethyl group, a propyl group, a butyl group, an isobutyl group, a pentyl group or a hexyl group.
The pharmaceutically acceptable salts of the indolo[2,3-b]quinoxaline derivative of Formula (I) refer to acid addition salts, which are those given by addition of a pharmacologically acceptable acid to the nitrogen atom in the molecule of the compound of Formula (I), and examples thereof are salts with mineral acids (e.g. hydrochloric acid, hydrobromic acid, hydroiodic acid, sulfuric acid, nitric acid or phosphoric acid), and salts with organic acids (e.g. acetic acid, oxalic acid, citric acid, tartaric acid, maleic acid, succinic acid, fumaric acid, p-toluenesulfonic acid, benzenesulfonic acid or methanesulfonic acid).
The indolo[2,3-b]quinoxaline derivatives of Formula (I) and the pharmaceutically acceptable salts thereof of the present invention can be prepared by reacting an intermediate of Formula (XII): ##STR4## wherein one of R.sup.13 and R.sup.14 is a hydrogen atom and the other is a formyl group, a chloromethyl group or a bromomethyl group, and R.sup.3 is as defined above, with an amine compound represented by Formula (XV): ##STR5## wherein R.sup.4 is a hydrogen atom or a methyl group, and R.sup.5, R.sup.6 and R.sup.7 are the same or different and are each a hydrogen atom, a straight or branched lower alkyl group, or a group represented by Formula (III): an acetyl group.
More specifically, the intermediate of Formula (XII) wherein one of R.sup.13 and R.sup.14 is a hydrogen atom and the other is a formyl group and the amine compound of Formula (XV) are heated to form an imino compound, which is then reduced with sodium borohydride or an alkoxy borohydride under heating to give a compound of Formula (I) as a salt-free form.
Furthermore, the intermediate of Formula (XII) wherein one of R.sup.13 and R.sup.14 is a hydrogen atom and the other is a chloromethyl group or a bromomethyl group is reacted with the amine compound of Formula (XV) under heating to give a compound of Formula (I) as a salt-free form.
An acid addition salt of the compound of Formula (I) can be obtained by treating the compound of Formula (I) with an acid such as hydrochloric acid. The acid addition salt is treated with an alkali compound to convert into a compound as a free form.
The intermediate of Formula (XII) ca

REFERENCES:
patent: 2627461 (1953-02-01), Friedman
patent: 4916124 (1990-04-01), Bergman et al.
patent: 4990510 (1991-02-01), Bergman et al.

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