Dihydroindolone compounds, a process for their preparation and pharmaceutical compositions containing them

A method of treating a condition selected from cancers of the colon, breast, liver, kidneys, brain, esophagus, melanomas, myelomas, cancers of the ovary, small cell lung cancers, cancers of the prostate and pancreas, and sarcomas in a subject in need thereof comprising administration of an effective amount of a compound selected from those of formula (I):

• wherein:
• m represents 1 or 2,
• n represents 1 or 2,
• A represents a pyrrolyl group which is unsubstituted or substituted by 1 to 3 linear or branched (C1-C6)alkyl groups,
• X represents a C(O), S(O) or SO2 group,
• R1 and R2, which are the same or different, each represent a linear or branched (C1-C6)alkyl group,
• or R1 and R2, together with the nitrogen atom carrying them, form a heterocyclic group,
• R3 and R4, together with the atoms carrying them, form a heterocyclic group,
• R5 represents a hydrogen atom or a linear or branched (C1-C6)alkyl group,
• R6 represents a hydrogen atom or a halogen atom,
• it being understood that:
• a “heterocyclic group” means a mono- or bi-cyclic group which may contain from 5 to 8 members, which may contain from one to three hetero atoms selected from nitrogen, oxygen and sulphur, and which may contain one or more unsaturated bonds, wherein the heterocyclic group is optionally substituted by one or more groups selected from linear or branched (C1-C6)alkyl, linear or branched (C1-C6)alkenyl, oxo, hydroxy, linear or branched (C1-C6)alkoxy, aryl, arylalkyl and Arylalkenyl,
• “aryl” means a phenyl group which is optionally substituted by one or more groups selected from halogen atoms and linear or branched (C1-C6)alkyl groups,
• the notation representing the exocyclic double bond at the 3-position of the indolone ring means that the double bond is of configuration Z or E,
• its optical and geometric isomers, and addition salts thereof with a pharmaceutically acceptable acid or base and an anticancer agent selected from genotoxic agents, mitotic poisons, antimetabolites, proteasome inhibitors and kinase inhibitors.

A method of treating a condition selected from cancers of the colon, breast, liver, kidneys, brain, esophagus, melanomas, myelomas, cancers of the ovary, small cell lung cancers, cancers of the prostate and pancreas, and sarcomas in a subject in need thereof comprising administration of an effective amount of a compound selected from those of formula (I):

• wherein:
• m represents 1 or 2,
• n represents 1 or 2,
• A represents a pyrrolyl group which is unsubstituted or substituted by 1 to 3 linear or branched (C1-C6)alkyl groups,
• X represents a C(O), S(O) or SO2 group,
• R1 and R2, which are the same or different, each represent a linear or branched (C1-C6)alkyl group,
• or R1 and R2, together with the nitrogen atom carrying them, form a heterocyclic group,
• R3 and R4, together with the atoms carrying them, form a heterocyclic group,
• R5 represents a hydrogen atom or a linear or branched (C1-C6)alkyl group,
• R6 represents a hydrogen atom or a halogen atom,
• it being understood that:
• a “heterocyclic group” means a mono- or bi-cyclic group which may contain from 5 to 8 members, which may contain from one to three hetero atoms selected from nitrogen, oxygen and sulphur, and which may contain one or more unsaturated bonds, wherein the heterocyclic group is optionally substituted by one or more groups selected from linear or branched (C1-C6)alkyl, linear or branched (C1-C6)alkenyl, oxo, hydroxy, linear or branched (C1-C6)alkoxy, aryl, arylalkyl and arylalkenyl,
• “aryl” means a phenyl group which is optionally substituted by one or more groups selected from halogen atoms and linear or branched (C1-C6)alkyl groups,
• the notation representing the exocyclic double bond at the 3-position of the indolone ring means that the double bond is of configuration Z or E,
• its optical and geometric isomers, and addition salts thereof with a pharmaceutically acceptable acid or base in combination with radiotherapy.