New disubstituted 3,4-diamino-3-cyclobutene-1,2-dione compounds useful in the treatment of chemokine-mediated pathologies

摘要

Disubstituted compound of 3,4-diamino-3-cyclobutene-1,2-dione which responds to the following general formula (I) or one of its pharmaceutically acceptable salts or solvates: ** Formula ** where R 1 represents an atom of hydrogen or a methyl; R2 represents a ring of five atoms selected from the following structures (1), (2), (3) and (4): ** Formula ** in which R5, R7a, X and X 'have the meaning to be given later; R3 represents an aromatic or heteroaromatic ring selected from the group consisting of the rings that respond to the following formulas (a) to (o): ** Formula ** in which R7, R7a, Y and Z have the meaning to be given later, specifying that the rings (a) to (o) may eventually carry several R7 groups, identical or different, the total number of such groups R7 being at most equal to the number of substitutable atoms in the ring; R4 represents an aromatic or heteroaromatic ring selected from the group consisting of the rings that respond to the following formulas (p) to (z) and (aa) to (ak): ** Formula ** in which R7, R8, R9 , R10, R11, R12, R13, R14 and R15 have the meaning that will be given later; R5 represents a hydrogen atom, a fluorine atom, an alkyl radical of 1 to 5 carbon atoms or a fluorinated or perfluorinated alkyl radical of 1 to 5 carbon atoms; R6 represents a hydrogen atom, a -COOtBu radical or a -COOBn radical; R7 represents a halogen, a radical -R16, -CF3, -COR16, -OR16, -NR16R17, -NO2, -CN, -SO2R16, -SO2NR16R17, -NR16COR17, -CONR16R17, -NR16CO2R17 or -CO2R16; R7a represents a hydrogen atom or an alkyl radical of 1 to 5 carbon atoms; R8 represents a hydrogen atom, a halogen atom, a radical -OH, a radical -SH, -CONHOR16, -CONR16OH, -NR16R17, -SO3H, -OCOR16, -NHSO2R16, -SO2NR16R17, -NHCOR16, -CONR16R17, - NR16CO2R17, -NHSO2NR16R17, -CO2R16, pyrrolyl, imidazolyl, triazolyl or tetrazolyl; R9, R10, R11 and R12 are identical or different and are independently selected from the group consisting of a hydrogen, a halogen atom, an alkyl radical, alkoxy, -CF3, -OCF3, -OH, -NO2, -CN, - SO2R16, -SO2NR16R17, -NR16COR17, -NR16CO2R17, -CONR16R17, -COR16 or -CO2R16; or also, when two of the radicals R9, R10, R11 and R12 are in ortho position in an aromatic or heteroaromatic ring selected from the group consisting of the rings that respond to formulas (p) to (z) and (aa) a (ak) above, then they can form together, with the joining together, an aryl, heteroaryl, cycloalkyl or heterocycloalkyl ring; R13 and R14 are identical or different and are independently selected from the group consisting of a hydrogen atom, a halogen atom, an alkyl radical, -CF3, -OCF3, -OH, -SH, -CN, -SO2R16, -SO2NR16R17 , -NHSO2NR16R17, -NR16R17, -NR16CONR16R17, -NR16COR17, -NR16CO2R17, -CONR16R17, -COR16 or -CO2R16; R15 represents a hydrogen atom, a radical -OH, -SO2R16, -COR16, -CO2R16, aryl, heteroaryl, arylalkyl, heteroarylalkyl, alkyl, cycloalkyl or cycloalkylalkyl; R16 and R17 are identical or different and are independently selected from the group consisting of a hydrogen atom, an aryl radical, heteroaryl, arylalkyl, heteroarylalkyl, alkyl, fluorinated alkyl of 1 to 5 carbon atoms, cycloalkyl or cycloalkylalkyl, a group - CH2COOR18 in which R18 represents an alkyl radical of 1 to 5 carbon atoms, or also, when R16 and R17 are carried by the same nitrogen atom, they form a heterocycle having between 3 and 7 links and eventually carrying one or two heteroatoms selected from oxygen, sulfur and nitrogen, in addition to the common nitrogen atom by which they are carried, said heterocycle may be substituted by an alkyl group of 1 to 5 carbon atoms or a -COOR18 group in which R18 represents an alkyl radical of 1 to 5 carbon atoms; X and X ', identical or different, represent an oxygen atom, a sulfur atom or a nitrogen atom substituted by a radical R6; Y represents an oxygen atom, a sulfur atom or a nitrogen atom substituted by a radical R15, and Z represents a carbon or nitrogen atom.