1-Azabicyclo[2.2.2]octan-3-one derivatives and maleimide derivatives and their use for treating cancer tumors
AssigneeAprea AB
InventorsVladimir Bykov, Galina Selivanova, Klas Wiman
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Abstract
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 tumors.
Claims9
Use of compounds that are able to restore the apoptosis-inducing function of mutant p 53 protein which compounds are chosen from compounds having the formula I
- 6
- wherein
- R2 or R3 are the same or different and are chosen from the group of hydrogen, C1-15 alkyl, C1-15 alkenyl, C1-15 alkynyl, C1-15 alkoxy, C1-15 alkylamino, aryl, C6-15 aryl alkyl, C1-15 alkyl carboxy, C2-15 alkyl alkyl carboxylate, C1-15 alkylthio, C1-15 alkyl hydroxy, wherein said groups optionally can be substituted with halogen or from 2-hydroxymethyl-3,3-dihydroxy-1-azabicyclo[2,2,2] octane and from compounds having the formula II
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- wherein
- R1 is chosen from the group of hydrogen, C1-15 alkyl, C1-15 alkenyl, C1-15 alkynyl, C1-15 alkoxy, C1-15 alkylamino, aryl, C6-15 aryl alkyl, C1-15 alkyl carboxy, C2-15 alkyl alkyl carboxylate, C1-15 alkylthio, C1-15 alkyl hydroxy, wherein said groups optionally can be substituted with halogen, for the preparation of a pharmaceutical for the treatment of conditions caused by mutant p53 protein.
Use of compounds having the formula I
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- wherein
- R2 or R3 are the same or different and are chosen from the group of hydrogen, C1-15 alkyl, C1-15 alkenyl, C1-15 alkynyl, C1-15 alkoxy, C1-15 alkylamino, aryl, C6-15 aryl alkyl, C1-15 alkyl carboxy, C2-15 alkyl alkyl carboxylate, C1-15 alkylthio, C1-15 alkyl hydroxy, wherein said groups optionally can be substituted with halogen or from 2-hydroxymethyl-3,3-dihydroxy-1-azabicyclo[2,2,2] octane for the preparation of a pharmaceutical for the treatment of cancer.
Use of compounds having the formula II
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- wherein
- R1 is chosen from the group of hydrogen, C1-15 alkyl, C1-15 alkenyl, C1-15 alkynyl, C1-15 alkoxy, C1-15 alkylamino, aryl, C6-15 aryl alkyl, C1-15 alkyl carboxy, C2-15 alkyl alkyl carboxylate, C1-15 alkylthio, C1-15 alkyl hydroxy, wherein said groups optionally can be substituted with halogen, for the preparation of a pharmaceutical for the treatment of cancer caused by mutant p53 protein.
Dependencies are inferred from the claim text.