Piperazine derivatives and process for the preparation thereof

Details Piperazine derivatives and process for the preparation thereof Piperazine derivatives and process for the preparation thereof

1998-02-27

2000-02-22

Bernhardt, Emily

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

Organic compounds

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

544363, 544364, 544389, 544390, 544252, 544253, 544255, C07D40112, A61K 31495

Patent

active

060281952

DESCRIPTION:

BRIEF SUMMARY
The present invention relates to new piperazine derivatives of the general formula (I) ##STR2## wherein R.sub.1 and R.sub.2 are independently hydrogen, substituted or unsubstituted C.sub.1 -C.sub.8 alkyl, substituted or unsubstituted C.sub.3 -C.sub.6 cycloalkyl, substituted or unsubstituted C.sub.2 -C.sub.8 unsaturated alkyl, ketone, substituted or unsubstituted aryl, substituted or unsubstituted C.sub.1 -C.sub.4 alkoxy, substituted or unsubstituted arylhydroxy, substituted or unsubstituted amino, C.sub.1 -C.sub.4 lower ester, C.sub.1 -C.sub.4 lower thioester, thiol, substituted or unsubstituted carboxyl, epoxy, substituted or unsubstituted C.sub.1 -C.sub.4 lower thioalkoxy; or R.sub.1 and R.sub.2 are fused to form C.sub.3 -C.sub.4 saturated or unsaturated chain; R.sub.3, R.sub.4, R.sub.5, R.sub.6 and R.sub.7 are independently hydrogen, halogen, hydroxy, nitro, C.sub.1 -C.sub.4 lower ester, C.sub.1 -C.sub.4 lower alkyl, C.sub.1 -C.sub.4 lower thioalkyl, substituted or unsubstituted C.sub.3 -C.sub.6 cycloalkyl, C.sub.1 -C.sub.4 lower alkoxy, C.sub.1 -C.sub.4 lower thioalkoxy, substituted or unsubstituted aryl, substituted or unsubstituted lower arylalkoxy, substituted or unsubstituted lower alkylamino, or lower alkyl substituted or unsubstituted carbamate; or among R.sub.3, R.sub.4, R.sub.5, R.sub.6 and R.sub.7, two adjacent groups are bonded with each other to form 1,2-phenylene or 2,3-naphthylene; X is oxygen, sulfur, or substituted or unsubstituted imino; Y is bonded at the 3-position or 4-position of the aromatic ring part wherein Y is oxygen or --NR.sub.8 -- (wherein, R.sub.8 is the same with the above-mentioned R.sub.3.); Z is hydroxy, C.sub.1 -C.sub.4 lower alkoxy, C.sub.1 -C.sub.4 lower thioalkoxy, substituted or unsubstituted aryloxy, C.sub.1 -C.sub.4 lower alkylamino, substituted or unsubstituted cycloamino containing 1-5 nitrogen atoms; A is nitrogen or --CH.dbd.; its pharmaceutically acceptable acid addition salts and process for the preparation thereof.
In the above definitions, C.sub.1 -C.sub.8 alkyl means straight or branched alkyl group such as methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, tert-butyl, pentyl, iso-pentyl, hexyl, heptyl, octyl, 2-methylpentyl or the like.
C.sub.1 -C.sub.4 lower alkyl means methyl, ethyl, propyl, iso-propyl, n-butyl, iso-butyl or tert-butyl.
Substituted or unsubstituted C.sub.3 -C.sub.6 cycloalkyl means substituted or unsubstituted cycloalkyl such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, substituted cyclopropyl, substituted cyclopentyl, substituted cyclohexyl or the like.
C.sub.1 -C.sub.4 lower ester means a carboxyl group esterified by a lower alkyl group.
C.sub.1 -C.sub.4 lower alkoxy means methoxy, ethoxy, propoxy, isopropoxy, butyloxy, isobutyloxy, tert-butyloxy group or the like.
C.sub.1 -C.sub.4 lower thioalkoxy means methylthio, ethylthio, propylthio, isopropylthio, butylthio, isobutylthio, tert-butylthio group or the like.
C.sub.1 -C.sub.4 lower alkylamino means methylamino, ethylamino, propylamino, butylamino group or the like.
Aryloxy means phenoxy, substituted phenoxy, naphthyloxy or substituted naphthyloxy or the like.
Cycloamino group containing 1-5 nitrogen atoms means pyrrolidinyl, pyrrolinyl, imidazolyl, imidazolidinyl, pyrazolyl, pyrazolinyl, pyrazolidinyl, triazolyl, tetrazolyl, piperazinyl or the like.
The present inventors had studied for a long time to find compounds having intensive antitumor activity. As the results, now we have finally found out the facts that the present compounds of the general formula(I) and acid addition salts thereof have not only prominent antitumor activities but very low toxicities.
Accordingly, the one object of the present invention is to provide the novel compounds of the general formula(I) and acid addition salts thereof having not only prominent antitumor activities but very low toxicities.
The other object of the present invention is to provide a process for the preparation of the compounds of general formula(I) and acid addition salts thereof.
The compounds of the present invention can b

REFERENCES:
patent: 4016274 (1977-04-01), Cotrel et al.
patent: 4038391 (1977-07-01), Cotrel et al.
patent: 5218002 (1993-06-01), Stroech et al.
patent: 5387593 (1995-02-01), Mattson et al.
patent: 5391571 (1995-02-01), Mewshaw et al.
patent: 5461047 (1995-10-01), Hansen, Jr. et al.
patent: 5478828 (1995-12-01), Mattson et al.
patent: 5482948 (1996-01-01), Soyka et al.
patent: 5780472 (1998-07-01), Cho et al.
patent: 5789412 (1998-08-01), Halazy et al.
Advanced Organic Chemistry by Jerry March (2nd Ed.) p. 378-379, 1977.
J. Med. Chem., 1992, 35, 3784-3791, Hoffman et al.
J. Med. Chem., 1992, 35, 3792-3802, Saari et al.
Chemical Abstracts, vol. 110, No. 4, Jan. 23, 1989 p. 499, Yoshimoto et al.

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