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US 7,923,434 B2Granted
Phosphole derivatives complexed with metals, and pharmaceutical uses thereof
AssigneeCentre National De La Recherche Scientifique
InventorsElisabeth Davioud-Charvet, Katja Becker-Brandenburg, Valérie Deborde, Régis Reau, R. Heiner Schirmer, Christel Herold-Mende
Life of this patent
Estimating the term…
Abstract
The invention concerns pharmaceutical compositions comprising as active compound at least one compound of general formula (A), wherein: M represents a metal atom, and their uses in particular for preventing or treating pathologies associated with an excess activity of glutathion reductase and/or thioredoxin reductase.
Claims26
A pharmaceutical composition, comprising as active ingredient at least one compound of general formula (I) below:
- in which:
- a is a single bond or no bond,
- R1 is a
- linear or branched alkyl group with 1 to 6 carbon atoms,
- saturated or unsaturated cycloalkyl group with 3 to 7 carbon atoms,
- aryl group with 6 to 14 carbon atoms,
- linear or branched alkoxy group with 1 to 6 carbon atoms,
- saturated or unsaturated cycloalkoxy group with 3 to 7 carbon atoms,
- aryloxy group with 6 to 14 carbon atoms,
- linear or branched alkylthio group with 1 to 6 carbon atoms,
- saturated or unsaturated cycloalkylthio group with 3 to 7 carbon atoms, or
- arylthio group with 6 to 14 carbon atoms,
- optionally substituted by one or more groups, identical or different, chosen from a halogen atom, a linear or branched alkyl group with 1 to 6 carbon atoms, optionally substituted by one or more halogen atoms, or an aryl group with 6 to 14 carbon atoms;
- R2 is a nitrogen-containing heteroaryl group or a nitrogen-containing heterocycle with 5 or 6 atoms having from 1 to 4 nitrogen atoms;
- R3 and R4 are, independently of one another, a hydrogen atom, or a
- linear or branched alkyl group with 1 to 6 carbon atoms,
- saturated or unsaturated cycloalkyl group with 3 to 7 carbon atoms,
- aryl group with 6 to 14 carbon atoms,
- linear or branched alkoxy group with 1 to 6 carbon atoms,
- saturated or unsaturated cycloalkoxy group with 3 to 7 carbon atoms,
- aryloxy group with 6 to 14 carbon atoms,
- linear or branched alkylthio group with 1 to 6 carbon atoms,
- saturated or unsaturated cycloalkylthio group with 3 to 7 carbon atoms, or
- arylthio group with 6 to 14 carbon atoms,
- optionally substituted by one or more groups, identical or different, chosen from a halogen atom, a linear or branched alkyl group with 1 to 6 carbon atoms, optionally substituted by one or more halogen atoms, or an aryl group with 6 to 14 carbon atoms, optionally an alkyl group can bridge the carbon atoms in positions 3 and 4 of the phosphole ring carrying, respectively, the substituents R3 and R4, so as to form a ring with 3 to 8 carbon atoms;
- R5 is a hydrogen atom, a heterocycle with five or six members having from 1 to 4 nitrogen or sulphur atoms, or a
- linear or branched alkyl group with 1 to 6 carbon atoms,
- saturated or unsaturated cycloalkyl group with 3 to 7 carbon atoms,
- aryl group with 6 to 14 carbon atoms,
- linear or branched alkoxy group with 1 to 6 carbon atoms,
- saturated or unsaturated cycloalkoxy group with 3 to 7 carbon atoms,
- aryloxy group with 6 to 14 carbon atoms,
- linear or branched alkylthio group with 1 to 6 carbon atoms,
- saturated or unsaturated cycloalkylthio group with 3 to 7 carbon atoms, or
- arylthio group with 6 to 14 carbon atoms,
- optionally substituted by one or more groups, identical or different, chosen from a halogen atom, a linear or branched alkyl group with 1 to 6 carbon atoms, optionally substituted by one or more halogen atoms, or an aryl group with 6 to 14 carbon atoms;
- M is a metal atom, optionally carrying from 1 to 2 substituents, R6 and R7, identical or different, which substituents are chosen from
- a halogen atom,
- a thio-osidic group with 3 to 60 carbon atoms, optionally substituted by one or more groups, identical or different, chosen from the protective groups of the hydroxyl or amine groups, chosen from an alkanoyl group with 2 to 6 carbon atoms, or an arylcarbonyl group with 6 to 14 carbon atoms,
- a peptide group comprising from 1 to 5 amino acids, at least one of the amino acids comprising a thio group, chosen from S-cysteine or S-glutathione, or
- a linear or branched thioalkyl group with 1 to 6 carbon atoms, a saturated or unsaturated thiocycloalkyl group with 3 to 7 carbon atoms or a thioaryl or thioheteroaryl group with 6 to 14 carbon atoms, optionally substituted by one or more groups, identical or different, chosen from a halogen atom, an alkyl group with 1 to 6 carbon atoms, optionally substituted by one or more halogen atoms, or an aryl group with 6 to 14 carbon atoms;
- in combination with a pharmaceutically acceptable vehicle.
39 more elements
A pharmaceutical composition, comprising as active ingredient at least one compound of general formula (I) below:
- in which:
- a is a single bond or no bond,
- R1 is a
- linear or branched alkyl group with 1 to 6 carbon atoms,
- saturated or unsaturated cycloalkyl group with 3 to 7 carbon atoms,
- aryl group with 6 to 14 carbon atoms,
- linear or branched alkoxy group with 1 to 6 carbon atoms,
- saturated or unsaturated cycloalkoxy group with 3 to 7 carbon atoms,
- aryloxy group with 6 to 14 carbon atoms,
- linear or branched alkylthio group with 1 to 6 carbon atoms,
- saturated or unsaturated cycloalkylthio group with 3 to 7 carbon atoms, or
- arylthio group with 6 to 14 carbon atoms,
- optionally substituted by one or more groups, identical or different, chosen from a halogen atom, a linear or branched alkyl group with 1 to 6 carbon atoms, optionally substituted by one or more halogen atoms, or an aryl group with 6 to 14 carbon atoms;
- R2 is a nitrogen-containing heteroaryl group or a nitrogen-containing heterocycle with 5 or 6 atoms having from 1 to 4 nitrogen atoms;
- R3 and R4 represent, independently of one another, a hydrogen atom, or a linear or branched alkyl group with 1 to 6 carbon atoms,
- saturated or unsaturated cycloalkyl group with 3 to 7 carbon atoms,
- aryl group with 6 to 14 carbon atoms,
- linear or branched alkoxy group with 1 to 6 carbon atoms,
- saturated or unsaturated cycloalkoxy group with 3 to 7 carbon atoms,
- aryloxy group with 6 to 14 carbon atoms,
- linear or branched alkylthio group with 1 to 6 carbon atoms,
- saturated or unsaturated cycloalkylthio group with 3 to 7 carbon atoms, or
- arylthio group with 6 to 14 carbon atoms,
- optionally substituted by one or more groups, identical or different, chosen from a halogen atom, a linear or branched alkyl group with 1 to 6 carbon atoms, optionally substituted by one or more halogen atoms, or an aryl group with 6 to 14 carbon atoms, optionally an alkyl group can bridge the carbon atoms in positions 3 and 4 of the phosphole ring carrying, respectively, the substituents R3 and R4, so as to form a ring with 3 to 8 carbon atoms;
- R5 is a hydrogen atom, a heterocycle with five or six members having from 1 to 4 nitrogen or sulphur atoms, or a
- linear or branched alkyl group with 1 to 6 carbon atoms,
- saturated or unsaturated cycloalkyl group with 3 to 7 carbon atoms,
- aryl group with 6 to 14 carbon atoms,
- linear or branched alkoxy group with 1 to 6 carbon atoms,
- saturated or unsaturated cycloalkoxy group with 3 to 7 carbon atoms,
- aryloxy group with 6 to 14 carbon atoms,
- linear or branched alkylthio group with 1 to 6 carbon atoms,
- saturated or unsaturated cycloalkylthio group with 3 to 7 carbon atoms, or
- arylthio group with 6 to 14 carbon atoms,
- optionally substituted by one or more groups, identical or different, chosen from a halogen atom, a linear or branched alkyl group with 1 to 6 carbon atoms, optionally substituted by one or more halogen atoms, or an aryl group with 6 to 14 carbon atoms;
- M is a metal atom, optionally carrying from 1 to 2 substituents, R6 and R7, identical or different, which substituents are chosen from
- a halogen atom,
- a thio-osidic group with 3 to 60 carbon atoms, optionally substituted by one or more groups, identical or different, chosen from the protective groups of the hydroxyl or amine groups, an alkanoyl group with 2 to 6 carbon atoms, or an arylcarbonyl group with 6 to 14 carbon atoms, or
- a peptide group comprising from 1 to 5 amino acids, at least one of the amino acids comprising a thio group, chosen from S-cysteine or S-glutathione, or
- a linear or branched thioalkyl group with 1 to 6 carbon atoms, a saturated or unsaturated thiocycloalkyl group with 3 to 7 carbon atoms or a thioaryl or thioheteroaryl group with 6 to 14 carbon atoms, optionally substituted by one or more groups, identical or different, chosen from a halogen atom, an alkyl group with 1 to 6 carbon atoms, optionally substituted by one or more halogen atoms, or an aryl group with 6 to 14 carbon atoms;
- in combination with a pharmaceutically acceptable vehicle.
38 more elements
A compound of general formula (IX) below:
- in which:
- a is a single bond or no bond,
- b is 0 or 1,
- R1 is a
- linear or branched alkyl group with 1 to 6 carbon atoms,
- saturated or unsaturated cycloalkyl group with 3 to 7 carbon atoms,
- aryl group with 6 to 14 carbon atoms,
- linear or branched alkoxy group with 1 to 6 carbon atoms,
- saturated or unsaturated cycloalkoxy group with 3 to 7 carbon atoms,
- aryloxy group with 6 to 14 carbon atoms,
- linear or branched alkylthio group with 1 to 6 carbon atoms,
- saturated or unsaturated cycloalkylthio group with 3 to 7 carbon atoms, or
- arylthio group with 6 to 14 carbon atoms,
- optionally substituted by one or more groups, identical or different, chosen from a halogen atom, a linear or branched alkyl group with 1 to 6 carbon atoms, optionally substituted by one or more halogen atoms, or an aryl group with 6 to 14 carbon atoms;
- R2 is a nitrogen-containing heteroaryl group or a nitrogen-containing heterocycle with 5 or 6 atoms having from 1 to 4 nitrogen atoms;
- R3 and R4 represent, independently of one another, a hydrogen atom, or a linear or branched alkyl group with 1 to 6 carbon atoms,
- saturated or unsaturated cycloalkyl group with 3 to 7 carbon atoms,
- aryl group with 6 to 14 carbon atoms,
- linear or branched alkoxy group with 1 to 6 carbon atoms,
- saturated or unsaturated cycloalkoxy group with 3 to 7 carbon atoms,
- aryloxy group with 6 to 14 carbon atoms,
- linear or branched alkylthio group with 1 to 6 carbon atoms,
- saturated or unsaturated cycloalkylthio group with 3 to 7 carbon atoms, or
- arylthio group with 6 to 14 carbon atoms,
- optionally substituted by one or more groups, identical or different, chosen from a halogen atom, a linear or branched alkyl group with 1 to 6 carbon atoms, optionally substituted by one or more halogen atoms, or an aryl group with 6 to 14 carbon atoms, optionally an alkyl group can bridge the carbon atoms in positions 3 and 4 of the phosphole ring carrying, respectively, the substituents R3 and R4, so as to form a ring with 3 to 8 carbon atoms;
- R5 is a hydrogen atom, a heterocycle with five or six members having from 1 to 4 nitrogen or sulphur atoms, or a
- linear or branched alkyl group with 1 to 6 carbon atoms,
- saturated or unsaturated cycloalkyl group with 3 to 7 carbon atoms,
- aryl group with 6 to 14 carbon atoms,
- linear or branched alkoxy group with 1 to 6 carbon atoms,
- saturated or unsaturated cycloalkoxy group with 3 to 7 carbon atoms,
- aryloxy group with 6 to 14 carbon atoms,
- linear or branched alkylthio group with 1 to 6 carbon atoms,
- saturated or unsaturated cycloalkylthio group with 3 to 7 carbon atoms, or
- arylthio group with 6 to 14 carbon atoms,
- optionally substituted by one or more groups, identical or different, chosen from a halogen atom, a linear or branched alkyl group with 1 to 6 carbon atoms, optionally substituted by one or more halogen atoms, or an aryl group with 6 to 14 carbon atoms;
- M is a divalent, trivalent or tetravalent metal atom, providing that when M is a divalent metal atom then a is no bond and b is 0, when M is a trivalent metal atom then a is no bond and b is 1 and that when M is a tetravalent metal atom then a is a single bond and b is 1,
- R6 is a thio-osidic group with 3 to 60 carbon atoms, optionally substituted by one or more groups, identical or different, chosen from the protective groups of the hydroxyl or amine groups, an alkanoyl group with 2 to 6 carbon atoms, or an arylcarbonyl group with 6 to 14 carbon atoms,
- R7 is
- a halogen atom,
- a thio-osidic group with 3 to 60 carbon atoms, optionally substituted by one or more groups, identical or different, chosen from the protective groups of the hydroxyl or amine groups, an alkanoyl group with 2 to 6 carbon atoms, or an arylcarbonyl group with 6 to 14 carbon atoms,
- a peptide group comprising from 1 to 5 amino acids, at least one of the amino acids comprising a thio group, chosen from S-cysteine or S-glutathione, or
- a linear or branched thioalkyl group with 1 to 6 carbon atoms, a saturated or unsaturated thiocycloalkyl group with 3 to 7 carbon atoms or a thioaryl or thioheteroaryl group with 6 to 14 carbon atoms, optionally substituted by one or more groups, identical or different, chosen from a halogen atom, an alkyl group with 1 to 6 carbon atoms, optionally substituted by one or more halogen atoms, or an aryl group with 6 to 14 carbon atoms.
40 more elements
Dependencies are inferred from the claim text.