4-Cyanopyrazole-3-carboxamide derivatives, preparation, and application thereof

A compound of formula (IIa):

• in which:
• R is hydrogen or (C1-C4)alkyl, and
• R3, R4, R5, R6, R7, R8 represent, each independently of the other, a hydrogen, halogen, a (C1-C6)alkyl, (C1-C6)alkoxy or trifluoromethyl;
• provided that at least one of the substituents R3, R4, R5 and at least one of the substituents R6, R7, R8 is different from hydrogen and provided that when R3 represents a methoxy group and R6 represents a bromine atom, the substituents R4, R5, R6, R7, R8 are different from hydrogen.

A pharmaceutical composition comprising a compound of formula (I) or a pharmaceutically acceptable salt, a hydrate or a solvate thereof, in combination with at least one pharmaceutically acceptable excipient:

• in which:
• R1 represents hydrogen or a (C1-C4)alkyl;
• R2 represents:
• a (C3-C7) alkyl;
• a nonaromatic C3-C10 carboxyl radical which is unsubstituted or substituted once or several times with a (C1-C4)alkyl or hydroxyl group;
• a phenyl which is substituted with one or more groups independently selected from a halogen, a (C1-C4)alkyl, trifluoromethyl or (C1-C4)alkoxy;
• an NR9R10 group;
• a CH[(C1-C4)alkyl]benzhydryl group in which one or both of the phenyl groups are unsubstituted or substituted once or several times with a halogen, a (C1-C4)alkyl or (C1-C4)alkoxy;
• or R1 and R2 together with the nitrogen atom to which they are attached constitute a piperidin-1-yl radical which is disubstituted at the 4-position with a phenyl, benzyl, a (C1-C4)alkyl or a (C1-C3) alkanoyl;
• R3, R4, R5, R6, R7, R8 represent, each independently of the other, a hydrogen, halogen, a (C1-C6)alkyl, (C1-C6)alkoxy or trifluoromethyl;
• provided that at least one of the substituents R3, R4, R5, R6, R7, R8 is different from hydrogen;
• R9 represents a hydrogen atom;
• R10 represents a (C3-C6)alkyl;
• or R9 and R10 together with the nitrogen atom to which they are attached constitute a saturated or unsaturated heterocyclic radical of 5 to 10 atoms, optionally containing a second heteroatom chosen from O or N, said radical being unsubstituted or substituted once or several times with a (C1-C4)alkyl, hydroxyl, (C1-C4)alkoxy, methoxy(C1-C2)alkylene, (C1-C4)alkanoyl group or substituted with a spirocyclobutane, a spirocyclopentane or a spirocyclohexane.