Radiohalogenated benzamide derivatives and their use in tumor diagnosis and tumor therapy

A method for the diagnosis and/or treatment of a tumor melanoma, comprising administering to a subject in need thereof an effective amount of a radiohalogenated compound of formula (I),

• in which
• X1 is an ether of formula —O—R3,
• X3 is a radical of formula —NR1R2,
• X2, X4 and X5 are, independently of one another, a halogen, hydrogen, a radical of formula —NR1R2, an ether of formula —O—R3, a branched or unbranched C1—C10 alkyl group, a branched or unbranched C2—C10 alkenyl group or an aryl or heteroaryl group that is optionally substituted by halogen or low alkoxy,
• wherein two adjacent radicals X1 to X5 may form a 5- to 7-membered ring, wherein one or more carbon atoms of the ring are optionally replaced by heteroatoms,
• X6 is an oxygen or —NH—,
• X7 and X8 are the same or different and are hydrogen, C1-12 alkyl, C2-12 alkenyl, C3-6 cycloalkyl, C3-6 cycloalkenyl, C2-6 carbalkoxyalkyl, C2-6 carbalkoxyalkenyl, C6-12 aryl or C6-12 heteroaryl;
• in each case optionally substituted in one or more places by OR4, COOR5, CONR6R7, cyano, halogen or NR8R9,
• or
• X7 and X8 together form a 5- to 7-membered ring, wherein one or more carbons of the ring are optionally replaced by heteroatoms,
• R1 and R2 are the same or different and are hydrogen, C1-12 alkyl, C2-12 alkenyl, C3-6 cycloalkyl, C3-6 cycloalkenyl, C2-6 carboxyalkyl, C2-6 carboxyalkenyl, C1-12 alkyl, C6-12 arylsulfonyl, carboxyaryl, carboxy heteroaryl;
• in each case optionally substituted in one or more places by aryl, heteroaryl, OR4, COOR5, CONR6R7, cyano, halogen or NR8R9, or two substituents taken together form a 3, 4, 5, 6, 7 or 8 membered ring, optionally with 1, 2, 3, or 4 hetero atoms,
• R3 is hydrogen, C6-12 aryl, heteroaryl, C1-10 alkyl, C2-10 alkenyl, C2-10alkinyl, C3-6cycloalkyl, C3-6 cycloalkenyl, in each case optionally substituted in one or more places by OR4, COOR5, CONR6R7, cyano, halogen or NR8R9,
• R4 and R5 are the same or different and are hydrogen, C1-12 alkyl, C2-12 alkenyl, C3-6 cycloalkyl, C3-6 cycloalkenyl, optionally substituted in one or more places by aryl, heteroaryl, OR10, COOR11, CONR6R7, cyano, halogen or NR8R9,
• R6, R7, R8 and R9 are the same or different and are hydrogen, C1-12 alkyl, C2-12 alkenyl, C3-6 cycloalkyl, C3-6 cycloalkenyl, in each case optionally substituted in one or more places by OR4, or R6 and R7 or R8 and R9 in each case together form a 5- to 7-membered ring, wherein one or more carbons of the ring are optionally replaced by heteroatoms, and
• R10 and R11 are the same or different and are hydrogen, C1-12 alkyl, C2-12 alkenyl, C3-6 cycloalkyl, C3-6 cycloalkenyl, which are optionally substituted in each case in one or more places by aryl, heteroaryl, OR4, COOR5, CONR6R7, cyano, halogen, or NR8R9,
• provided that
• R1 and R2 cannot simultaneously be hydrogen,
• at least one of radicals X2, X4 and X5 is a radioactive halogen,
• at least one of radicals X2, X3, X4 and X5 is a radical of formula —NR1R2, in which either R1 or R2 is a substituted or unsubstituted radical carboxyalkyl, carboxyalkenyl carboxyaryl or carboxyheteroaryl, and
• with the proviso that if X1 is methoxy and X6 is oxygen, X8 is hydrogen and X7 is NH(CH2)2NEt2, and X4 is I131, X3 is not NHAc, or a pharmaceutically acceptable salt thereof.