Aminotropane derivatives, preparation thereof and therapeutic use thereof

A compound corresponding to formula (I):

• in which:
• Ra and Ra′, which may be identical to or different from one another, represent a hydrogen atom, or an alkyl or cycloalkyl group,
• R1 represents a hydrogen atom, or an alkyl, cycloalkyl, heterocycloalkyl or aryl group,
• R2 represents a group of formula —(CH2)x—(CO)y—Y or —(CO)y—(CH2)x—Y, in which:
• x=0, 1, 2, 3 or 4,
• y=0 or 1,
• Y represents a hydrogen atom, or a hydroxyl, alkyl, cycloalkyl, alkoxy, aryl, heteroaryl or —NR11R12 group, Y being different from a hydrogen atom when x=y=0,
• R11 and R12 which may be identical to or different from one another, represent a hydrogen atom, or an alkyl, cycloalkyl, alkoxy or —NR13R14 group, or else R11 and R12 form, together with the nitrogen atom to which they are attached, a mono- or bicyclic structure containing from 4 to 10 ring members and optionally comprising 1 to 3 additional hetero atoms and/or 1 to 3 ethylenic or acetylenic unsaturations, this ring being optionally substituted in any of the positions with 1 to 3 groups chosen from halogen atoms, and hydroxyl, alkyl, cycloalkyl and alkoxy groups,
• R13 and R14, which may be identical to or different from one another, represent a hydrogen atom, or an alkyl, cycloalkyl or alkoxy group, or else R13 and R14 form, together with a nitrogen atom to which they are attached, a mono- or bicyclic structure as defined above,
• R3 represents 1 to 3 groups, which may be identical to or different from one another, located in any positions of the ring to which they are attached and chosen from halogen atoms, and alkyl, cycloalkyl, —OR, —NRR′, —CO—NRR′, —NR—CO—R′, —NR—CO—NRR′, —NR—COOR′, —NO2, —CN and —COOR groups,
• R5 represents a hydrogen atom or an alkyl,
• R4 is chosen from:
• (1) a group of formula (a), (b) or (c) optionally substituted with an oxo group:
• in which each of the rings of formulae (a), (b) and (c) may be substituted, in any positions, with 1 to 4 groups R7, which may be identical to or different from one another, and in which:
• a=0, 1, 2 or 3,
• p=0, 1, 2 or 3,
• m=0, 1 or 2,
• X represents an oxygen or sulphur atom, or a ring member —C(R6)(R7)— or —N(R10)—,
• R6 is chosen from:
• a hydrogen atom, a halogen atom,
• a group —(CH2)x—OR8, —(CH2)x—COOR8, —(CH2)x—NR8R9, —(CH2)x—CO—NR8R9 or —(CH2)x—NR8—COR9, in which x=0, 1, 2, 3 or 4,
• an alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, alkylaryl, alkylheteroaryl, —CO-alkyl, —CO-cycloalkyl, —CO-heterocycloalkyl, —CO-aryl, —CO-heteroaryl, —CO-alkylaryl, —CO-alkylheteroaryl, —CS-alkyl, —CS-cycloalkyl, —CS-heterocycloalkyl, —CS-aryl, —CS-heteroaryl, —CS-alkylaryl, —CS-alkylheteroaryl, —CS—NR8R9 or —C(═NH)—NR8R9 group,
• a fused or nonfused cycloalkyl or heterocycloalkyl group located in the spiro position on the ring of formula (a) to which it is attached,
• a cycloalkyl or heterocycloalkyl group fused with an aryl or heteroaryl group,
• R7 is chosen from hydrogen and halogen atoms, and alkyl, cycloalkyl, aryl, heteroaryl, alkylaryl, alkylheteroaryl, —OR, —O-aryl, —O-heteroaryl, —O-alkyl-aryl, —O-alkylheteroaryl, —NRR′, —CO—NRR′, —NR—CO—R′, —NR—CO—NRR′, —NR—COOR′, —NO2, —CN and —COOR groups,
• R8 and R9 are chosen, independently of one another, from a hydrogen atom, and alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, alkylaryl, alkyl-heteroaryl, —CO-alkyl, —CO-cycloalkyl, —CO-hetero-cycloalkyl, —CO-aryl, —CO-heteroaryl, —CO-alkylaryl, —CO-alkylheteroaryl, —SO2-alkyl, —SO2-cycloalkyl, —SO2-heterocycloalkyl, —SO2-aryl, —SO2-heteroaryl, —SO2-alkylaryl, —SO2-alkylheteroaryl, —C(═NH)—NRR′, —COOR, —CO—NRR′, —CS—NRR′ and —(CH2)x—OR groups, where x=0, 1, 2, 3 or 4;
• or else R8 and R9 together form a cycloalkyl or a heterocycloalkyl;
• R10 is chosen from:
• a hydrogen atom,
• a group —(CH2)x—OR8, —(CH2)x—COOR8, —(CH2)x—NR8R9, —(CH2)x—CO—NR8R9, —(CH2)x—NR8—COR9 or —(CH2)x—COR8, in which x=0, 1, 2, 3 or 4,
• a cycloalkyl or heterocycloalkyl group fused with an aryl or heteroaryl group,
• an alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, alkylaryl, alkylheteroaryl, —CO-alkyl, —CO-cycloalkyl, —CO-heterocycloalkyl, —CO-aryl, —CO-heteroaryl, —CO-alkylaryl, —CO-alkylheteroaryl, —CS-alkyl, —CS-cycloalkyl, —CS-heterocycloalkyl, —CS-aryl, —CS-heteroaryl, —CS-alkylaryl, —CS-alkylheteroaryl, —CS—NR8R9, —C(═NH)—NR8R9, —SO2-alkyl, —SO2-cycloalkyl, —SO2-heterocycloalkyl, —SO2-aryl, —SO2-heteroaryl, —SO2-alkylaryl, —SO2-alkylheteroaryl or —SO2—NR8R9 group,
• or else R10 forms, with the nitrogen atom to which it is attached and a carbon atom located in any position of the cyclic structure of formula (a), but not adjacent to said nitrogen atom, a bridge comprising from 3 to 5 members,
• R and R′ represent, independently of one another, a hydrogen atom, or an alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, alkylaryl or alkylheteroaryl group,
• the alkyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl groups being optionally substituted with one or more groups chosen from the groups R, R′, —OR, —NRR′, —CO—NRR′, —NR—CO—R′, —NR—CO—NRR′, —NO2, —CN and —COOR, OCOR, COR, OCONRR′, NRCOOR′,
• (2) a group of formula -A-R18, -A-CH═N—R19, -A-N(R20)-A′-R19, -A-CO—N(R20)-A′-R19, -A-CH(NH2)—R19 or -A-N(R20)—COO-A′, in which A and A′ represent a linear or branched alkyl group, R18 represents a halogen atom, or an —NH2, hydroxyl or phenyl group, R19 represents a hydrogen atom, or a hydroxyl, phenyl, benzyl or heteroaryl group, and R20 represents a hydrogen atom or a benzyl group,
• (3) a group of formula (d):
• optionally substituted, in any positions, with 1 to 4 groups R7, which may be identical to or different from one another, as defined above, and in which r is equal to 1, 2 or 3, s is equal to 0 or 1, and one of U, V or W represents a nitrogen atom, the others among U, V and W representing methylene ring members, or
• (4) a —(CH2)r-heteroaryl group, where r is equal to 1, 2 or 3,
• in the form of a base or of an addition salt with an acid, and also in the form of a hydrate or of a solvate.