Labelled analogues of halobenzamides as radiopharmaceuticals

A method for the diagnosis and/or treatment of melanoma comprising the administration to a patient suffering from melanomas of an effect amount of a compound of formula (I):

• in which
• R1 represents a radionuclide,
• Ar represents an aromatic nucleus,
• m is an integer varying from 2 to 4,
• R2 and R3 represent, independently of one another, a hydrogen atom, a (C1-C6)alkyl group, a (C1-C6)alkenyl group or an aryl group chosen from a phenyl, benzyl, imidazolyl, pyridyl, pyrimidinyl, pyrazinyl, indolyl, indazolyl, furyl and thienyl group,
• in which the aromatic nucleus denotes an aryl group chosen from the naphthyl, phenanthryl and anthryl group or a heteroaryl group, optionally the heteroaryl group is mono- or disubstituted by:
• an optionally labelled halogen atom,
• a hydroxyl group,
• a (C1-C4)alkyl group
• a (C1-C4)alkoxy group,
• an —NO2 group,
• an —NR5R6 group, where R5 and R6 can independently represent a hydrogen atom or a (C1-C4)alkyl group,
• an —NHCONH2 group,
• an —SH group,
• an —NHCOOR7, —NHCONHR7 or —SR7 group, where R7 represents a (C1-C4)alkyl group,
• an oxo group, or
• monosubstituted by an anilino group which can itself be substituted by 1 to 3 groups which can be chosen from a (C1-C4)alkyl or (C1-C4)alkoxy group, a hydroxyl group, a halogen atom or an NHRe group where Re represents a hydrogen, or a CORa group, a COORa group or an SO2Ra group, where Ra represents an aryl group or a (C1-C10)alkyl group optionally substituted by an oxo group,
• and in which R1 is bonded to the aromatic nucleus as such or, when the substituent of the aromatic nucleus is an anilino group, R1 can be bonded to the phenyl group of the anilino group,
• or one of their addition salts with pharmaceutically acceptable acids.

A method for the treatment of melanomas, comprising the administration to a patient suffering from melanomas of an effective amount of a compound of formula (I′)

• in which
• W is chosen from a phenazinyl, imidazopyridyl, quinolyl, quinoxalinyl, acridinyl and acridonyl group,
• it being possible for the said acridinyl group to be substituted by an anilino group itself substituted by three groups,
• at least one of the substituents representing the (C1-C4)alkoxy group,
• at least one of the substituents being chosen from an NHRe group where Re represents a hydrogen, or a CORa group, a COORa group or an SO2Ra group, where Ra represents an aryl group or a (C1-C10)alkyl group optionally substituted by an oxo group, and
• the remaining substituent representing a hydrogen or halogen atom,
• R1 represents a radionuclide,
• m is an integer varying from 2 to 4,
• R2 and R3 represent, independently of one another, a hydrogen atom, a (C1-C6)alkyl group, a (C1-C6)alkenyl group or an aryl group chosen from a phenyl, benzyl, imidazolyl, pyridyl, pyrimidinyl, pyrazinyl, indolyl, indazolyl, furyl and thienyl group, and
• R8 represents a hydrogen atom, a (C1-C4)alkyl or (C1-C4)alkoxy group, an optionally labelled halogen atom, an —SH group, an —OH group or an —NR5R6 group where R5 and R6 can independently represent a hydrogen atom or a (C1-C4)alkyl group,
• in the preparation of a composition intended for the treatment of melanoma.

Compound of formula (II)

• in which
• R′1 represents a labelled halogen atom,
• m is an integer varying from 2 to 4,
• R2 and R3 represent, independently of one another, a hydrogen atom, a (C1-C6)allyl group, a (C1-C6)alkenyl group or an aryl group chosen from a phenyl, benzyl, imidazolyl, pyridyl, pyrimidinyl, pyrazinyl, indolyl, indazolyl, furyl and thienyl group, and
• Ar is chosen from the naphthyl, pyridyl, benzothienyl, indolyl, isoindolyl, quinolyl, isoquinolyl, quinoxalinyl, benzimidazolyl, indazolyl, phthalazinyl, quinazolinyl, cinnolinyl, carbazolyl, phenanthrolinyl, carbolinyl, perimidinyl, benzisoquinolinyl, naphthyridinyl, quinolizinyl, purinyl, imidazopyridinyl, indolizinyl, pteridinyl, imidazotriazinyl and pyrazinopyridazinyl group, it being possible for the said group to be mono- or disubstituted by a (C1-C4)alkyl or (C1-C4)alkoxy group or an optionally labelled halogen atom.

Compound of formula (I″)

• in which
• m is an integer varying from 2 to 4,
• R2 and R3 represent, independently of one another, a hydrogen atom, a (C1-C6)alkyl group, a (C1-C6)alkenyl group or an aryl group chosen from a phenyl, benzyl, imidazolyl, pyridyl, pyrimidinyl, pyrazinyl, indolyl, indazolyl, furyl and thienyl group,
• R8 represents a hydrogen atom, a (C1-C4)alkyl or (C1-C4)alkoxy group, an optionally labelled halogen atom, an —SH group, an —OH group or an —NR5R6 group where R5 and R6 can independently represent a hydrogen atom or a (C1-C4)alkyl group, and
• W is chosen from a phenazinyl, imidazopyridyl, quinolyl, quinoxalinyl, acridinyl and acridonyl group, and the iodine atom is optionally labelled.

Compound of formula (VII)

• in which
• Ar represents an aromatic nucleus,
• m is an integer varying from 2 to 4,
• R2 and R3 represent, independently of one another, a hydrogen atom, a (C1-C6)alkyl group, a (C1-C6)alkenyl group or an aryl group chosen from a phenyl, benzyl, imidazolyl, pyridyl, pyrimidinyl, pyrazinyl, indolyl, indazolyl, furyl and thienyl group,
• in which the aromatic nucleus denotes an aryl group chosen from the naphthyl, phenanthryl and anthryl group or a heteroaryl group, optionally the heteroaryl group is mono- or disubstituted by:
• an optionally labelled halogen atom,
• a hydroxyl group,
• a (C1-C4)alkyl group
• a (C1-C4)alkoxy group,
• an —NO2 group,
• an —NR5R6 group, where R5 and R6 can independently represent a hydrogen atom or a (C1-C4)alkyl group,
• an —NHCONH2 group,
• an —SH group,
• an —NHCOOR7, —NHCONHR7 or —SR7 group, where R7 represents a (C1-C4)alkyl group,
• an oxo group, or
• monosubstituted by an anilino group which can itself be substituted by 1 to 3 groups which can be chosen from a (C1-C4)alkyl or (C1-C4)alkoxy group, a hydroxyl group, a halogen atom or an NHRe group where Re represents a hydrogen, or a CORa group, a COORa group or an SO2Ra group, where Ra represents an aryl group or a (C1-C10)alkyl group optionally substituted by an oxo group.