Use of low molecular weight compounds for preparing a medicament useful in treating mutant p53 mediated diseases
The present invention provides novel compounds, corresponding to formulae I and II, respectively, which are able to reactivate the apoptosis-inducing function of mutant p53 proteins. This reactivation is provided by restoration of sequence-specific DNA-binding activity and transcriptional transactivation function to mutant p53 proteins, and modulation of the conformation-dependent epitopes of the p53 protein. Accordingly, the substances according to the invention will be used in pharmaceutical compositions and methods for treatment of patients suffering from various types of tumours.
1. A method of treating a mutant p53 mediated cancer selected from the group consisting of osteosarcoma, lung adenocarcinoma, Burkitt lymphoma, ovarian carcinoma and colon carcinoma, comprising:
administrating to a mammal in need thereof a pharmaceutically efficient amount of a compound selected from compounds having a structure according to the formula I
wherein:
R1 is hydrogen or a methylene group, which can be double bonded, as indicated by the broken line, or single bonded and linked to the nitrogen atom of an amine-substituted phenyl group, to a nitrogen atom contained in the ring structure of a purine, 8-azapurine, or benzimidazol residue, and;
A is an oxygencontaining moiety, either consisting of an oxygen atom being double bonded, as indicated by the broken line, or a benzoyloxy group, with the proviso that when A is a benzoyloxy group, then R1 is hydrogen.
2. The method of claim 1 , wherein the compound is combined with a pharmaceutically acceptable carrier, diluent and/or excipient.