Indazolamides with analgesic activity

A process for preparing an indazolamide of formula I:

• wherein
• X is an NHC(O) or C(O)NH group,
• R1 is a hydrogen or halogen atom, or an aminocarbonyl, acetylamino, sulphonylmethyl, aminosulphonylmethyl, linear or branched C1-3 alkyl or C1-3 alkoxy group,
• R2 is a hydrogen atom or a linear or branched C1-3 alkyl group or an aryl(C1-3)alkyl group in which the abovementioned groups are optionally substituted with one or more substituents selected from the group consisting of halogen atoms, C1-3 alkyl and C1-3 alkoxy,
• R3 and R4, which may be identical or different, are a hydrogen or halogen atom, or an amino, nitro, hydroxyl, linear or branched C1-3 alkyl, C1-3 alkoxy, di(C1-3)alkylamino, acetylamino or O—(C1-3)alkylphenyl group, or R3 and R4, together, form a 5- to 7-membered ring in which one or two of the said members may be a hetero atom selected from the group consisting of N, S and O,
• R5, R6, R7 and R8, which may be identical or different, are H or methyl;
• and acid-addition salts thereof with pharmaceutically acceptable organic and mineral acids,
• wherein it comprises the following stages:
• a) condensing an amine of formula (II)
• in which
• X, R3, R4, R5, R6, R7 and R8 have the meanings given above,
• with an indazolecarboxylic acid derivative of formula (IIIa)
• in which
• R1 and R2 have the meanings given above, and
• Y is a chlorine or bromine atom, or a group OR or OC(O)R, in which R is an alkyl with a linear or branched chain comprising from 1 to 6 carbon atoms, or of formula (IIIb)
• in which
• R1 has the meanings given above,
• to give the indazolamide of formula (I), and
• b) optionally, forming an acid-addition salt of the indazolamide of formula (I) with a pharmaceutically acceptable organic or mineral acid.

A pharmaceutical composition containing an effective amount of a compound of formula (I):

• wherein
• X is an NHC(O) or C(O)NH group,
• R1 is a hydrogen or halogen atom, or an aminocarbonyl, acetylamino, sulphonylmethyl, aminosulphonylmethyl, linear or branched C1-3 alkyl or C1-3 alkoxy group,
• R2 is a hydrogen atom or a linear or branched C1-6 alkyl group or an aryl(C1-3)alkyl group in which the abovementioned groups are optionally substituted with one or more substituents selected from the group consisting of halogen atoms, C1-3 alkyl and C1-3 alkoxy,
• R3 and R4, which may be identical or different, are a hydrogen or halogen atom, or an amino, nitro, hydroxyl, linear or branched C1-3 alkyl, C1-3 alkoxy, di(C1-3)alkylamino, acetylamino or O—(C1-3)alkylphenyl group, or R3 and R4, together, form a 5- to 7-membered ring in which one or two of the said members may be a hetero atom selected from the group consisting of N, S and ),
• R5, R6, R7 and R8, which may be identical or different, are H or methyl;
• or of an acid-addition salt thereof with a pharmaceutically acceptable acid, and
• at least one pharmaceutically acceptable inert ingredient.

An intermediate of formula (II)

• wherein
• X is an NHC(O) or C(O)NH group,
• R3 and R4, which may be identical or different, are a hydrogen or halogen atom, or an amino, nitro, hydroxyl, linear or branched C1-3 alkyl, C1-3 alkoxy, di(C1-3)alkylamino, acetylamino or O—(C1-3)alkylphenyl group, or R3 and R4, together, form a 5- to 7-membered ring in which one or two of the said members may be a hetero atom selected from the group consisting of N, S and O,
• R5, R6, R7 and R8, which may be identical or different, are H or methyl.