US 12,202,804 B2
In vitro or ex vivo methods for screening a quinoline derivative
Didier Scherrer, Castelnau le Lez (FR); and Jamal Tazi, Clapiers (FR)
Assigned to ABIVAX, Paris (FR); CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE, Paris (FR); INSTITUT CURIE, Paris (FR); and UNIVERSITE DE MONTPELLIER, Montpellier (FR)
Filed by ABIVAX, Paris (FR); CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE, Paris (FR); INSTITUT CURIE, Paris (FR); and UNIVERSITE DE MONTPELLIER, Montpellier (FR)
Filed on May 17, 2022, as Appl. No. 17/746,410.
Application 17/746,410 is a division of application No. 16/994,954, filed on Aug. 17, 2020, granted, now 11,649,210.
Application 16/994,954 is a division of application No. 16/554,748, filed on Aug. 29, 2019, granted, now 10,981,874, issued on Apr. 20, 2021.
Application 16/554,748 is a division of application No. 15/326,755, granted, now 10,435,370, issued on Oct. 8, 2019, previously published as PCT/EP2015/066458, filed on Jul. 17, 2015.
Claims priority of application No. 14306164 (EP), filed on Jul. 17, 2014.
Prior Publication US 2022/0315535 A1, Oct. 6, 2022
Int. Cl. C07D 215/38 (2006.01); A61K 31/47 (2006.01); A61K 31/4709 (2006.01); A61K 31/497 (2006.01); A61K 31/5377 (2006.01); C07D 401/12 (2006.01); C12Q 1/6883 (2018.01); G01N 33/50 (2006.01)
CPC C07D 215/38 (2013.01) [A61K 31/47 (2013.01); A61K 31/4709 (2013.01); A61K 31/497 (2013.01); A61K 31/5377 (2013.01); C07D 401/12 (2013.01); C12Q 1/6883 (2013.01); G01N 33/5023 (2013.01); G01N 33/5055 (2013.01); C12Q 2600/136 (2013.01); C12Q 2600/158 (2013.01); C12Q 2600/178 (2013.01)] 19 Claims
 
1. 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)

OG Complex Work Unit Chemistry
or a pharmaceutically acceptable salt thereof,
wherein:
Z is C or N,
V is C or N,

OG Complex Work Unit Chemistry
 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):

OG Complex Work Unit Chemistry
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.