ngCycloartanone derivatives with anticancer activity

The compound of following formula (I):

• or a pharmaceutically acceptable salt thereof,
• wherein:
• indicates a single bond or a double bond,
• X1 and X2 represent, independently of each other, an oxygen or sulfur atom,
• R1 represents an oxygen atom, a sulfur atom or an N—OR11 or N—NHCO—NH2 group,
• R2 represents a hydrogen atom or an OR12 or SR12 group,
• R3 represents a hydrogen atom, —SO2R55, —CH2OCH2CH2SiR61R62R63, a —CO—(C1-C6)alkyl, or —CO—(C2-C6)alkenyl group, wherein said group is optionally substituted by a halogen atom or a COOH or NR56R57 group,
• R4 represents a group selected from:
• a hydrogen atom,
• a saturated or unsaturated linear or branched hydrocarbon chain comprising 1 to 15 carbon atoms, one or more non-consecutive carbon atoms may be replaced by an oxygen atom, wherein said chain is optionally substituted by one or more groups selected from a halogen atom, ═O, —OH, —OSO2R13, —N3, (C1-C6)alkoxy, —Z1C(X)R14, —C(X)Z2R15, —Z3C(X)Z4R16, —NH—OR17, ═N—OR18, ═N—NR53R54, —OSiR19R20R21, —SiR58R59R60, —OP(O)(OR22)(OR23), —NR24R25, a heterocycle with 5 or 6 members, an epoxide, a sugar residue and an inositol residue, one or more hydroxy groups of said sugar and inositol residues are optionally substituted by an acetyl group or —P(O)(OH)2, and
• a heterocycle with 5 or 6 members or a polycycle with 10 to 15 members, wherein said heterocycle or polycycle comprises at least one oxygen atom and is optionally substituted by one or more groups selected from —OH, ═O, —NH2, —N3, ═CH2, —COOR26, (C2-C6)alkenyl, (C1-C6)alkoxy, and a (C1-C6)alkyl group optionally substituted by a halogen atom or an —N3, —OH, (C1-C6)alkoxy, —NHCOR27 or —NR28—OC(O)R29 group,
• R5 and R6 each represent a hydrogen atom when represents a double bond, or R5 and R6 each represent, independently of each other, a hydrogen atom or an OR48 group, or R5 and R6 together form, with the carbon atoms that carry them, an epoxide ring, when represents a single bond,
• R7 represents a hydrogen atom or a OR49 group,
• R8 represents a hydrogen atom, or
• R7 and R8 together form, with the carbon atoms that carry them, an epoxide ring,
• R9 represents a —CO—(C1-C6)alkyl or —CO—(C2-C6)alkenyl group, or
• R9 and R4 together form a bond, or R9 forms a bond with the carbon atom of the R4 group located in the a position relative to carbon atom 22,
• R10 represents a hydrogen atom, or
• R10 and R3 together form a bond, or
• R10 and R9 together form a bond,
• with:
• R11, R26, R28, R30, R31, R36, R37, R41, R42, R43, R48, R49 and R50 representing, independently of one another, a hydrogen atom or a (C1-C6)alkyl, (C2-C6)alkenyl, aryl or aryl-(C1-C6)alkyl group,
• R12 representing a hydrogen atom or a (C1-C6)alkyl or (C2-C6)alkenyl group,
• R13 and R55 represent, independently of each other, an —OH, (C1-C6)alkoxy, aryl, —NR30R31 or (C1-C6)alkyl-aryl group, or a (C1-C6)alkyl group optionally substituted by an —NR30R31 group,
• R14 representing a (C1-C6)alkyl, (C2-C6)alkenyl, aryl, (C1-C6)alkyl-aryl or aryl -(C1-C6)alkyl group, wherein said group is optionally substituted by a group selected from a halogen atom, an —NR32—[(CH2)a—NR33]d—[(CH2)b—NR34—(CH2)c—N—R35]e—R52, —P(O)(OH)2 or —COOH group, with a, b and c representing an integer between 1 and 5 and d and e each representing 0 or 1,
• R15 and R16 representing, independently of each other, a hydrogen atom or a (C1-C6)alkyl, (C2-C6)alkenyl, aryl, (C1-C6)alkyl-aryl or aryl-(C1-C6)alkyl group, wherein said group is optionally substituted by a group selected from a halogen atom, an —NR32—[(CH2)a—NR33]d—[(CH2)b—NR34—(CH2)c—N—R35]e—R52 or —COOH group, with a, b, c, d and e as defined above,
• R17 and R18 representing, independently of each other, a hydrogen atom or a (C1-C6)alkyl, (C2-C6)alkenyl, aryl or aryl-(C1-C6)alkyl group,
• R19, R20, R21, R58, R59, R60, R61, R62 and R63 representing, independently of one another, a (C1-C6)alkyl, (C2-C6)alkenyl or aryl group,
• R22 and R23, identical or different, representing a hydrogen atom or a (C1-C6)alkyl or (C2-C6)alkenyl group, wherein said group is optionally substituted by an —OC(O)—(C1-C6)alkyl, NR36R37 and —N+R38R39R40 group, or R22 and R23 together form, with the oxygen atoms that carry them and the phosphorous atom, a ring,
• R24 and R25, representing, independently of each other, a hydrogen atom or a —CO—(C1-C6)alkyl, —CO—(C2-C6)alkenyl, (C2-C6)alkenyl, (C3-C7)cycloalkyl or (C1-C6)alkyl group optionally substituted by an NR41R42 group, or R24 and R25 together form, with the nitrogen atom that carries them, a heterocycle with 5 or 6 members, wherein said heterocycle may comprise, in addition to the nitrogen atom carrying R24 and R25, one or more heteroatoms selected from nitrogen, oxygen and sulfur, and is optionally substituted by a (C1-C6)alkyl group,
• R27 representing an aryl, (C1-C6)alkyl or (C2-C6)alkenyl group, wherein said group is optionally substituted by one or more halogen atoms,
• R29 representing a (C1-C6)alkyl, (C2-C6)alkenyl, aryl or aryl-(C1-C6)alkyl group,
• R32, R33, R34, R35, R52, R53, R54, R56 and R57 representing, independently of one another, a hydrogen atom or a (C1-C6)alkyl, (C2-C6)alkenyl,—CO—(C1-C6)alkyl, —CO—(C2-C6)alkenyl, —CO2—(C1-C6)alkyl or —CO2—(C2-C6)alkenyl group,
• R38, R39 and R40 representing, independently of one another, a (C1-C6)alkyl or (C2-C6)alkenyl group,
• X representing O, S or NR50,
• Z1, Z2, Z3 and Z4 representing, independently of one another, O or NR43, or Z2R15 and/or Z4R16 representing, independently of each other, a heterocycle with 5 or 6 members optionally substituted by a (C1-C6)alkyl group, wherein the heterocycle comprises at least one nitrogen atom by which it is linked to the rest of the molecule.