Pharmaceutical compositions comprising 4-quinolones for treating cancers

A method for modulating the proliferation of clonogenic cells in a tumor of a patient, comprising administering to said patient an effective amount of a compound chosen from the compounds of formulae:

• in which:
• R1 is chosen from H, OH, C1-C4 alkyl groups, C2-C4 alkenyl groups, C1-C4 alkoxy groups, phenyl groups or a phenyl group substituted 1 to 3 times with groups chosen from H, OH, a group —OCOR7, wherein R7 is a C1-C4 alkyl group, a group —O—SO2-R′7, wherein R′7 is a C1-C4 alkyl group or a CF3 group, and a group —NR16R17, wherein R16 and R17 are chosen, independently of each other, from hydrogen, C1-C4 alkyl groups, C2-C4 alkenyl groups, phenyl(C1-C4) alkyl groups or a phenyl(C1-C4) alkyl group substituted 1 to 3 times on the alkyl group with groups chosen from H, OH and C1-C4 alkoxy, or a dimethylamino (C1-C4) alkyl group, or together forming, with the nitrogen atom, a 5- or 6-membered heterocycle optionally comprising one or more hetero atoms chosen from oxygen, nitrogen and sulfur, or a methylpiperazinyl group;
• R2, R3 and R4 are chosen, independently of each other, from H, OH, a C1-C4 alkyl group, a C1-C4 alkoxy group, a group —OCO—R7, and a group derived from a saccharide, at least one of the substituents R2, R3 or R4 being other than H, and optionally R2 and R3 together forming a methylenedioxy group;
• R5 is a phenyl group or a phenyl group substituted 1 to 3 times with groups chosen from H, a C1-C4 alkoxy group, a group —OCOR7, a phenyl (C1-C4) alkoxy group, a group —O—SO2—R′7, wherein R′7 is a C1-C4 alkyl group or a CF3 group, a berzylamino group and a group derived from a saccharide;
• R6 is chosen from H, a C1-C4 alkyl group, a C2-C4 alkenyl group, a group —CO—R8 and a group —A—R9,
• R6a is chosen from a C1-C4 alkyl group, a C2-C4 alkenyl group, a group —CO—R8 and a group —A—R9,
• R8 is a C1-C4 alkyl group,
• A is a C1-C4 alkylene group,
• R9 is chosen from 5- or 6-membered heterocyclic groups containing 1 to 4 hetero atoms chosen from oxygen, sulfur and nitrogen, CN, hydroxyl, —COOR10 and —CONR11R12 groups, a group —NR13R14, a group —COR15 and a group OSO2R16,
• R10, R11, R12, R13, R14 and R15 are independently chosen from a hydrogen atom, C1-C4 alkyl group and a phenyl(C1-C4) alkyl group,
• R16 is chosen from a phenyl group and a (C1-C4) alkylphenyl group;
• and
• optionally R4 and R6 together forming a —CO—CH2—CH2-group.

A compound of formula:

• in which:
• R1 is chosen from H, OH, C1-C4 alkyl groups, C2-C4 alkenyl groups, C1-C4 alkoxy groups, phenyl groups or a phenyl group substituted 1 to 3 times with groups chosen from H, OH, a group —OCOR7, wherein R7 is a C1-C4 alkyl group, a group —O—SO2—R′7, R′7 being a C1-C4 alkyl group or a CF3 group, and a group —NR16R17, wherein R16 and R17 are chosen, independently of each other, from hydrogen, C1-C4 alkyl groups, C2-C4 alkenyl groups, phenyl(C1-C4)alkyl groups, a phenyl(C1-C4)alkyl group substituted 1 to 3 times on the alkyl group with groups chosen from H, OH and C1-C4 alkoxy, or a dimethylamino (C1-C4)alkyl group, or together forming, with the nitrogen atom, a 5- or 6-membered heterocycle optionally comprising one or more hetero atoms chosen from oxygen, nitrogen and sulfur, or a methylpiperazinyl group;
• R2, R3 and R4 are chosen, independently of each other, from H, OH, a C1-C4 alkyl group, a C1-C4 alkoxy group, a group —OCO—R7, and a group derived from a saccharide, optionally R2 and R3 together forming a methylenedioxy group;
• R5 is a phenyl group or a phenyl group substituted 1 to 3 times with groups chosen from H, a C1-C4 alkoxy group, a group —OCOR7, a phenyl(C1-C4)alkoxy group, a group —O—SO2—R′7, wherein R′7 is a C1-C4 alkyl group or a CF3 group, a benzylamino group and a group derived from a saccharide;
• R6 is chosen from H, a C1-C4 alkyl group, a C2-C4 alkenyl group, a group —CO—R8 and a group —A—R9;
• R6a is chosen from a C1-C4 alkyl group, a C2-C4 alkenyl group, a group —CO—R8 and a group —A—R9;
• R8 is a C1-C4 alkyl group;
• A is a C1-C4 alkylene group;
• R9 is chosen from 5- or 6-membered heterocyclic groups containing 1 to 4 hetero atoms chosen from oxygen, sulfur and nitrogen, CN, hydroxyl, —COOR10 and —CONR11R12 groups, a group —NR13R14, a group —COR15 and a group OSO2R16;
• R10, R11, R12, R13, R14 and R15 is independently chosen from a hydrogen atom, a C1-C4 alkyl group and a phenyl(C1-C4)alkyl group;
• R16 is chosen from a phenyl group and a (C1-C4)alkylphenyl group;
• and
• optionally R4 and R6 together forming a —CO—CH2—CH2— group, with the exclusion of the compounds in which:
• R1, R2, R4, R6=H, R3=OH and R5 is a phenyl, 4-methoxyphenyl, 2,4-dimethoxyphenyl or 2,5-dimethoxyphenyl group;
• R1=OH or OCH3, R2=H, R3=OCH3, R4=H, R5=4-methoxyphenyl and R6=H;
• R1=OCH3, R2=H, R3=OCH3, R4=H, R5=4-methoxyphenyl and R6=CH3;
• R1=OH, R2=H, R3=OH, R4=H, R5=4-hydroxyphenyl and R6=CH3;
• R1=H, R2=H, R3=OCH3, R4=H, R5=phehyl and R6=H;
• R1=H, R2=H, R3=OCH3, R4=H, R5=phenyl and R6=CH3;
• R1=H, R2=H, R3=OH, R4=OCH3, R5=phenyl and R6=H;
• R1, R2, R3, R4, R6=H and R5=phenyl or 4-methoxyphenyl;
• R1, R2, R3, R4, =H, R5=phenyl or 4-methoxyphenyl and R6=COCH3;
• R1, R2, R3, R4, =H, R5=phenyl and R6=CH3;
• R1, R2, R3, R4, R6=H and R5=4-methoxyphenyl, 2-methoxyphenyl or 4-methylphenyl;
• or
• R1=OH, R2, R3, R4=H and R5=phenyl, 4-methoxyphenyl, 2,4-ethoxyphenyl or 2,5-dimethylphenyl.