In vitro or ex vivo methods for screening a quinoline derivative

An in vitro or ex vivo method for screening a quinoline derivative, or a pharmaceutically acceptable salt thereof, presumed effective in treating and/or preventing an inflammatory disease, comprising:

• a) providing an eukaryotic cell,
• b) bringing into contact said cell with the quinoline derivative or the pharmaceutically acceptable salt thereof,
• c) measuring an expression of miR-124 in said cell, and
• d) selecting the quinoline derivative or the pharmaceutically acceptable salt thereof presumed effective in treating and/or preventing an inflammatory disease when the level of expression of miR-124 measured in step c) is increased relatively to a reference value,
• wherein the quinoline derivative is a compound of formula (I)
• or a pharmaceutically acceptable salt thereof,
• wherein:
• Z is C or N,
• V is C or N,
• means an aromatic ring wherein V is C or N and when V is N, V is in ortho, meta or para of Z and forms respectively a pyridine, a pyridazine, a pyrimidine or a pyrazine group,
• R independently represents a hydrogen atom, a halogen atom or a group chosen among a —CN group, a hydroxyl group, a (C1-C3) fluoroalkyl group, a (C1-C3) fluoroalkoxy group, a (C3-C6) cycloalkyl group, a —NO2 group, a —NR1R2 group, a (C1-C4) alkoxy group, a phenoxy group, a —NR1—SO2—NR1R2 group, a —NR1—SO2—R1 group, a —NR1—C(═O)—R1 group, a —NR1—C(═O)—NR1R2 group, a —SO2—NR1R2 group, a —SO3H group, a —O—SO2—OR3 group, a —O—P(═O)—(OR3) (OR4) group, a —O—CH2—COOR3 group and a (C1-C3) alkyl group, said alkyl being optionally mono-substituted by a hydroxyl group,
• Q is N or O, provided that R″ does not exist when Q is O,
• R1 and R2 are independently a hydrogen atom or a (C1-C3) alkyl group,
• R3 and R4 independently represent a hydrogen atom, Li+, Na+, K+, N+(Ra)4 or a benzyl group,
• n is 1, 2 or 3,
• n′ is 1, 2 or 3,
• R′ independently represents a hydrogen atom or a group chosen among a (C1-C3) alkyl group, a halogen atom, a —NO2 group, a —NR1R2 group, a morpholinyl group, a morpholino group, a N-methylpiperazinyl group, a (C1-C3) fluoroalkyl group, a —O—P(═O)—(OR3) (OR4) group, a —CN group, a group of formula (IIa), and a group of formula (IIIa):
• A is a covalent bond, an oxygen atom or NH,
• B is a covalent bond or NH,
• m is 1, 2, 3, 4 or 5,
• p is 1, 2 or 3,
• Ra and Rb independently represent a hydrogen atom, a (C1-C5) alkyl group or a (C3-C6) cycloalkyl group,
• Ra and Rb can further form together with the nitrogen atom to which they are attached a saturated 5- or 6-membered heterocycle optionally containing a further heteroatom chosen among N, O and S, said heterocycle being optionally substituted by one or more Ra, provided that when R′ is a group of formula (IIa) or a group of formula (IIIa), n′ may be 2 or 3 only if other R′ groups are different from said group of formula (IIa) or said group of formula (IIIa), and
• R″ is a hydrogen atom, a (C1-C4) alkyl group or is a group of formula (IIa) as defined above.