Condensed indan derivatives and salts thereof

Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...

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546 61, C07D22118

Patent

active

057634530

DESCRIPTION:

BRIEF SUMMARY
This application is a 371 of PCT/JP96/02195 filed Aug. 2, 1996.


TECHNICAL FIELD

The present invention relates to novel condensed indan derivatives and salts thereof. The compounds of the invention have excellent antitumor activity and are useful as antitumor agents.


BACKGROUND ART
have a skeleton similar to that of the compound of the present invention include, for example, compounds disclosed in Pol. J. Chem., 55, 121-128 (1981), Pol. J. Pharmacol. Pharm., 35 327-332 (1983), ibid., 35 523-530 (1983) and ibid., 38 221-227 (1986). Specifically stated, these documents disclose compounds substituted at the 10-position by a lower alkylamino group which may have a substituent, a phenylamino group, etc. These documents, however, refer to only anti-inflammatory and analgetic effects as pharmacological activity of said compounds, and do not report or disclose antitumor activity. Accordingly, the antitumor activity of the condensed indan derivatives of the present invention has not been found yet.
An object of the present invention is to provide a compound which has excellent antitumor activity and is useful as a therapeutic agent for tumors. Another object of the invention is to provide the use of said compound or salts thereof as an antitumor agent, and a method for treating tumors using said compound or a salt thereof. A further object of the invention is to provide a method for preparing said compound.


DISCLOSURE OF THE INVENTION

The inventors of the present invention conducted extensive research and found that condensed indan derivatives have excellent antitumor activity and are useful as antitumor agents. The present invention has been accomplished based on this finding.
The present invention provides a condensed indan derivative represented by the formula (1): ##STR2## wherein the ring A is an optionally substituted benzene ring or a benzene ring which has lower alkylenedioxy group(s), the ring B is an optionally substituted benzene ring or a benzene ring which has lower alkylenedioxy group(s), and R is a group --NR.sub.1 R.sub.2, an optionally substituted nitrogen-containing heterocyclic group, a group --OR.sub.3 or a group --SR.sub.4 (wherein R.sub.1 and R.sub.2 are the same or different and each represent a hydrogen atom, a phenyl group, an optionally substituted nitrogen-containing heterocyclic group, or a lower alkyl group which may be substituted by optionally substituted amino group(s), lower alkoxy group(s), phenyl group(s), nitrogen-containing heterocyclic group(s) or hydroxyl group(s), and R.sub.3 and R.sub.4 each represent a lower alkyl group which may be substituted by substituted amino group(s)), provided that at least one of the rings A and B is a substituted benzene ring and R is not --NHCH.sub.3, or a salt thereof.
The compound of the present invention represented by the formula (1) has excellent antitumor activity and is useful for treating various tumors.
The present invention provides a composition comprising an effective amount of the compound of the formula (1) or a phamaceutically acceptable salt thereof and a pharmaceutical carrier.
In particular, the present invention provides an antitumor agent comprising an effective amount of the compound of the formula (1) or a pharmaceutically acceptable salt thereof and a pharmaceutical carrier.
The present invention further provides a method for treating tumors in mammals comprising administering to mammals an effective amount of the compound of the formula (1) or a pharmaceutically acceptable salt thereof.
The groups represented by R, R.sub.1, R.sub.2, R.sub.3 and R.sub.4 and other groups shown in the present specification are described below more specifically.
Examples of the substituents in the benzene rings represented by the rings A and B include a halogen atom, a lower alkyl group, a lower alkoxy group, a hydroxyl group, a nitro group, an amino group, a lower acyloxy group, a benzyloxy group, a lower acylamino group, a cyano group, a carboxyl group, a lower alkoxycarbonyl group, etc. Among them, a lower alkoxy group and a hydroxy

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