Cancer targeting using carbonic anhydrase isoform ix inhibitors
AssigneesStichting Maastricht Radiation Oncology “Maastro-Clinic”, Universite Montpellier 2 Sciences Et Techniques, Claudiu Supuran
InventorsPhilippe Lambin, Jean-Yves Winum, Claudiu Supuran
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Abstract
The present invention concerns novel carbonic anhydrase IX inhibitors comprising a nitroimidazole moiety and their use in therapy of hypoxic conditions, in particular cancer treatment, especially chemotherapy and radiotherapy. The compounds of the invention have an increased specificity for the carbonic anhydrase IX enzyme compared to the art. The present invention relates to novel nitroimidazole derivates represented by formula (1), wherein R1, R2, and Z are as defined herein:
Claims17
1-35. (canceled)
A method of treating a subject afflicted with a disease characterized by overexpression of one or more carbonic anhydrase enzymes, comprising administering to the subject an effective amount of a compound, or a pharmaceutically acceptable salt thereof, of formula (1):
- wherein Z is Z1 with formula (2a):
- or Z is Z2 with formula (2b):
- (CH2)nCH2X, where X=sulfonamide, sulfamate or sulfamide;
- or
- or Z is Z3 with formula (2c):
- wherein R1 and R2 are, each independently, H, alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclic, aryl, cyano or halogen atom;
- R3, R4, R6 and R7 are, each independently H, alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclic, aryl, halogen atom, cyano, alkoxy, sulfonamide, sulfamate or sulfamide;
- R5 is sulfonamide, sulfamate or sulfamide;
- Y=O or S;
- and
- n=0, 1, 2, 3, 4 or 5.
A method of treating a subject afflicted with a disease characterized by overexpression of one or more carbonic anhydrase enzymes, comprising administering to the subject an effective amount of a compound, or a pharmaceutically acceptable salt thereof, of formula (1),
- wherein the compound is a compound of formula (3a)
- a compound of formula (3b)
- wherein X=sulfonamide, sulfamate or sulfamide;
- or a compound of formula (3c)
- wherein R1 and R2 are, each independently, H, alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclic, aryl, cyano or halogen atom;
- R3, R4, R6 and R7 are, each independently H, alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclic, aryl, halogen atom, cyano, alkoxy, sulfonamide, sulfamate or sulfamide;
- R5 is sulfonamide, sulfamate or sulfamide;
- Y=O or S;
- and
- n=0, 1, 2, 3, 4 or 5.
Dependencies are inferred from the claim text.