Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Patent
1996-03-27
1998-02-10
Rotman, Alan L.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
514292, 546 79, 546 81, C07D22106, C07D47104, A61K 3144, A61K 3145
Patent
active
057169632
DESCRIPTION:
BRIEF SUMMARY
CROSS-REFERENCE
This application is a 371 of PCT/ES95/00024.
TECHNICAL FIELD OF THE INVENTION
The present invention fits in the technical field of products with antitumor activity, used to make medicines to treat cancer in the different manifestations thereof.
More specifically, the present invention refers to a series of new anthraquinonic derivatives with important antitumor activity.
PRIOR ART OF THE INVENTION
Diazaquinomycin A is a 1,8-diazaanthraquinone found during the routine study of secondary metabolites coming from bacteria (S. Omura et al., J. Antibiotics, 35, 1425 (1982); and S. Omura et al. Tetrahedron Letters, 24, 3643 (1963)). Said product, which has the following formula (1) ##STR2## shows goods activity against Gram positive bacteria, due to its capacity to inhibit thymidilate synthetase (S. Omura et al., J. Antibiotics, 38, 1016 (1985); and M. Murata et al. T. Miyasaka, H. Tanaka, S. Omura, J. Antibiotics, 38, 1025 (1985)). However, Diazaquinomycin is inactive as an antitumor agent.
Japanese patent no. 63 79.830 describes Diazaquinomycin derivatives of formulae (2) and (3): ##STR3## wherein R.sup.1 and R.sup.2 have, among others, the meanings (CH.sub.2).sub.n CO.sub.2 R.sup.3, CH.sub.2 CH(CO.sub.2.sup.3).sub.2, etc. or else one of R.sup.1 and R.sup.2 is methyl and the other is (CH.sub.2).sub.n CO.sub.2 R.sup.3, CO.sub.2 CH(CO.sub.2 R.sup.3).sub.2, etc. n being=O-2 and R.sup.3 =hydrogen or C.sub.1-6 alkyl, that have shown usefulness as anticarcinogenic and antibacterial agents.
The compounds of formulae (4), (5), (6) and (7) (Omura, J. Antibiotics, 42, 727, 1989): ##STR4## X.dbd.H, BNr, OH, CN, CH(CO.sub.2 Et).sub.2 which have shown antitumor activity in cytotoxicity studies and in vitro studies, have also been described.
On the other hand, the applicant has studied large amounts of Diazaquinomycin derivatives that have shown antitumor activity, among which those of formula (8) ##STR5## described in British patent application no. 9212000.5 of 5 Jun. 1992, that also have antitumor activity, also deserve special mention.
Following along these lines, the present invention provides new anthraquinonic derivatives with important antitumor activity.
DETAILED DESCRIPTION OF THE INVENTION
The present invention relates to new anthraquinonic derivatives with antitumor activity and to the applications thereof.
The new compounds provided by the present invention correspond to the general formula (I) ##STR6## wherein the broken line represents a double bond that may or may not be present and A and B form, together with the center ring, an anthraquinonic system that responds to the following pairs of meanings of A and B: ##STR7## the broken line representing a double bond in all cases except in (a) in which said double bond is not present.
In accordance with the above, the present invention provides new anthraquinonic derivatives with antitumor activity that respond to the following formulae (I-a) to (I-e): ##STR8##
The present invention also provides pharmaceutical compositions that comprise one or more compounds of formula (I-a) to (I-1) in association with a solvent or pharmaceutically acceptable carrier.
The invention additionally provides the use of one or several of the compounds of formulae (I-a) to (I-1) in the manufacture of an antitumor drug. Finally, the invention provides a method to treat tumors using the compounds of formulae (I-a) to (I-1).
The compounds of the present invention are characterized in that they have excellent antitumor activity, as can be inferred from the biological activity studies carried out with the same and that are set forth hereinafter.
EMBODIMENTS OF THE INVENTION
The present invention is additionally illustrated by means of the following Examples, which do not seek to be restrictive of the scope hereof.
EXAMPLE 1
Preparation of
4,6,7-trimethyl-5,8,8a,10a-tetrahydro-1H-1-azaathracen-2,9,10-trione (I-a)
A solution of 4-methyl-1H-quinolin-2,5,8-trione (223 mg., 1,2 mmol) and 2,3-dimethyl-1,3-butadiene (106 mg, 1,3 mmol) was heated in ethyl acetate (
REFERENCES:
patent: 1882867 (1932-10-01), Ochs
patent: 1942407 (1934-03-01), Black
patent: 4300243 (1981-11-01), Baumgartner
Avendano Lopez Carmen
Garcia Gravalos Dolores
Rotman Alan L.
Universidad Complutense de Madrid
LandOfFree
Anthraquinonic derivatives having an antitumor activity and appl does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Anthraquinonic derivatives having an antitumor activity and appl, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Anthraquinonic derivatives having an antitumor activity and appl will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-2077599