Chemokine CXCR1 and CXCR2 receptor antagonist compounds, and use thereof in the treatment of chemokine-mediated pathologies

A method of treating an α-chemokine-mediated disease selected from the group consisting of psoriasis, atopic dermatitis, acne, and rosacea, the method comprising administering an effective amount of a compound corresponding to the general formula (I) below, or a salt thereof or an enantiomer thereof:

• in which:
• A represents
• B represents
• with
• R1′ and R2′, which are identical or different, represent a hydrogen, a halogen, a C1 to C5 alkyl which is unsubstituted or substituted with one or more fluorine atoms, a C1 to C5 alkoxy, OCF3, OH, CN or NR11R12,
• R1 and R2, which are identical or different, represent:
• a hydrogen,
• a C1 to C5 alkyl, which is unsubstituted or substituted with one or more groups selected from the group consisting of F, OH, OCH3 and NR11R12;
• R11 and R12 having the meaning given below, it being understood that when the C1 to C5 alkyl radical is substituted only with one or more fluorine atoms, it is a C1 to C5 fluoroalkyl radical or perfluoroalkyl radical,
• a C1 to C5 alkyl in which a carbon atom is replaced with an oxygen atom or with a sulfur atom, said C1 to C5 alkyl being unsubstituted or substituted with one or more groups selected from the group consisting of F, OH and NR11R12, R11 and R12 having the meaning given below,
• a C3 to C8 cycloalkyl radical,
• a C2 to C5 alkyne, which is unsubstituted or substituted with one or more groups selected from the group consisting of F, OH, phenyl and NR11R12, R11 and R12 having the meaning given below,
• a cycloalkyl corresponding to one of the formulae (1), (2), (3), (4), (5) or (6) below in which R5′, X and X′ have the meanings given below:
• an aromatic or heteroaromatic ring selected from the group consisting the rings corresponding to formulae (a) to (o) below in which R7, R7a, Y and have the meanings given below:
• R7 can be present several times on a ring, and at most as many times as there are substitutable atoms;
• the meanings of each substituent R7 are identical or different,
• R3 represents a hydrogen, a halogen, a C1 to C5 alkyl, a C1 to C5 alkoxy, —CF3, —OCF3, —OH, —NO2 or —CN,
• R4 and R5, which are identical or different, represent:
• a hydrogen,
• a C1 to C8 alkyl, which is unsubstituted or substituted with one or more groups selected from the group consisting of F, OH and NR11 R12, R11 and R12 having the meaning given below,
• a C1 to C8 alkyl in which a carbon atom is replaced with a nitrogen atom, with an oxygen atom or with a sulfur atom, said C1 to C8 alkyl being unsubstituted or substituted with one or more groups selected from the group consisting of F, OH and NR11R12, R11 and R12 having the meaning given below,
• a C3 to C8 cycloalkyl radical,
• a C3 to C8 cycloalkyl radical, one of the carbon atoms of which is replaced with an oxygen atom or with a nitrogen atom substituted with a radical R7a,
• a heterocycloalkyl of 5 to 7 ring atoms,
• a cycloalkylalkyl, the cycloalkyl being C3 to C8 and the alkyl C1 to C8,
• a phenyl,
• a phenyl substituted with a radical R7,
• a heteroaryl,
• an arylalkyl, the alkyl being C1-C5,
• a heteroarylalkyl, the alkyl being C1-C5,
• or alternatively
• R4 and R5 represent a chain —(CH2)m— forming a ring containing from 5 to 8 atoms with the sulfur and nitrogen atoms to which they are respectively attached, one of the carbons of the ring being optionally replaced with an oxygen or sulfur atom or with a nitrogen atom substituted with a radical R8;
• m and R8 having the meanings given below,
• R5′ represents a hydrogen atom, a fluorine, an alkyl radical comprising from 1 to 5 carbon atoms inclusive or a fluoroalkyl or perfluoroalkyl radical comprising from 1 to 5 carbon atoms,
• R6 represents a hydrogen atom, a radical —COOtBu or a radical —COOBn,
• R7 represents a hydrogen, a C1 to C3 alkyl, a halogen, —CF3, —CORS, —OR9, —NR9R10, —NO2, —CN, —SO2R9, —S(O)R9, —S(═O)(═NR9)R10′, —SO2NR9R10, —NR9S02R10, —NR9COR10, —NR9CO2R10, —CONR9R10 or —CO2R9,
• R7a represents a hydrogen or a C1 to C5 alkyl,
• R8 represents a hydrogen, —OH, —SO2R9, —CORS, —CO2R9, an aryl, a heteroaryl, an arylalkyl, a heteroarylalkyl, an alkyl, a cycloalkyl or alternatively a cycloalkylalkyl,
• R9 and R10 are identical or different and are selected from the group consisting of a hydrogen, an aryl, a heteroaryl, an arylalkyl, a heteroarylalkyl, an alkyl, a cycloalkyl and a cycloalkylalkyl,
• or alternatively
• R9 and R10 can be linked together when they are borne by the same nitrogen atom so as to form a 3- to 7-membered heterocycle comprising one or two heteroatoms chosen from oxygen, sulfur and nitrogen in addition to the nitrogen atom to which they are attached,
• R10′ represents an aryl, a heteroaryl, an arylalkyl, a heteroarylalkyl, an alkyl, a cycloalkyl or a cycloalkylalkyl,
• R11 and R12, which are identical or different, represent a hydrogen, a C1 to C5 alkyl, a C3 to C6 cycloalkyl, or a chain —(CH2)p— forming a ring containing from 4 to 6 atoms with the nitrogen atom to which they are attached,
• X and X′, which are identical or different, represent an oxygen atom, a sulfur atom or a nitrogen atom substituted with a radical R6,
• Y represents an oxygen atom, a sulfur atom or a nitrogen atom substituted with a radical R8,
• Z represents a carbon atom or a nitrogen atom,
• m=3, 4, 5 or 6 and
• p=3, 4 or 5.