# US 11,992,499 B2 · Quinoline derivatives for use in the treatment of inflammation diseases

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- Number: US 11,992,499 B2
- Document ID: US11992499B2
- Status: Granted
- Kind: B2
- Application number: 17/416,856
- Filed: 2019-12-19
- Published: 2022-01-27
- Granted: 2024-05-28
- Earliest claimed: 2018-12-20
- Assignees: Abivax; Institut Curie; Universite De Montipellier; Centre National De La Recherche Scientifique
- Applicants: Abivax; Institut Curie; Universite De Montpellier; Centre National De La Recherche Scientifique
- Inventors: Philippe Pouletty; Hartmut Ehrlich; Didier Scherrer; Jamal Tazi
- Web page: https://patentgrep.com/patent/US11992499B2

## CPC

- A61K 31/47: Quinolines; Isoquinolines
- A61K 31/706: containing six-membered rings with nitrogen as a ring hetero atom
- A61K 31/4709: Non-condensed quinolines and containing further heterocyclic rings
- A61K 31/497: containing further heterocyclic rings
- A61K 31/5377: not condensed and containing further heterocyclic rings, e.g. timolol
- A61P 1/16: for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
- A61P 9/12: Antihypertensives
- A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- C07H 17/02: Heterocyclic radicals containing only nitrogen as ring hetero atoms
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- C07H: SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS (derivatives of aldonic or saccharic acids C07C, C07D; aldonic acids, saccharic acids C07C59/105, C07C59/285; cyanohydrins C07C255/16; glycals C07D; compounds of unknown constitution C07G; polysaccharides, derivatives thereof C08B; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification C12N15/00; sugar industry C13)

## Abstract

A compound of Formula (I): or anyone of its metabolites or a pharmaceutically acceptable salt thereof, for use for treating and/or preventing an inflammatory disease, disorder or condition, wherein each R is independently hydrogen, halogen, —CN, hydroxyl, (C1-C3)fluoroalkyl, (C1-C3)fluoroalkoxy, (C3-C6)cycloalkyl, —NO2, —NR1R2, (C1-C4)alkoxy, phenoxy, —NR1—SO2—NR1R2, —NR1—SO2—R1, —NR1—C(═O)—R1, —NR1—C(═O)—NR1R2, —SO2—NR1R2, —SO3H, —O—SO2—OR3, —O—P(═O)—(OR3)(OR4), —O—CH2—COOR3, (C1-C3)alkyl; each R′ is independently hydrogen, (C1-C3)alkyl, hydroxyl, halogen, —NO2, —NR1R2, morpholinyl, morpholino, N-methylpiperazinyl, (C1-C3)fluoroalkyl, (C1-C4)alkoxy, —O—P(═O)—(OR3)(OR4), —CN, a —NH—SO2—N(CH3)2 group, or other groups and further relates to A compound of formula (IV): or a pharmaceutically acceptable salt thereof, for use for treating and/or preventing an inflammatory disease, disorder or condition, wherein V, Z, R, R′, n, and n′ are as described above.

## Claims

### Claim 1

A method for treating an inflammatory disease, disorder or condition comprising administering a compound to a patient suffering from the inflammatory disease, disorder or condition, wherein the compound is 8-Chloro-N-(4-(trifluoromethoxy)phenyl)quinolin-2-amine or a pharmaceutically acceptable salt thereof,
wherein the inflammatory disease, disorder or condition being treated by the administration of the compound is selected from the group consisting of:
(a) an inflammatory disease, disorder, or condition in the pancreas selected from diabetes type-1, diabetes type-2, acute and chronic pancreatitis;
(b) an inflammatory disease, disorder, or condition in the kidney selected from glomerulosclerosis, glomerulonephritis, nephritis, acute kidney injury, Berger's disease, Goodpasture's syndrome, Wegener's granulomatosis and kidney transplant acute or chronic rejection;
(c) an inflammatory disease, disorder, or condition in the liver selected from nonalcoholic steatohepatitis (NASH), non-alcoholic fatty liver disease (NAFUD), cholestatic liver disease, sclerosing cholangitis and liver transplant acute or chronic rejection;
(d) an inflammatory disease, disorder, or condition in the lung or heart selected from chronic obstructive pulmonary disease (COPD), pulmonary fibrosis, pulmonary hypertension, sarcoidosis, myocarditis, pericarditis and lung or heart transplant acute or chronic rejection;
(e) an inflammatory disease, disorder, or condition in the skin selected from contact dermatitis, atopic dermatitis, alopecia areata, erythema multiforma, dermatitis herpetiformis, scleroderma, vitiligo, hypersensitivity angiitis, uticaria, bullous pemphigoid, pemphigus vulgaris, pemphigus foliaceus, paraneoplastic pemphigus, epidermolysis bullosa acquisita, acnea and keloid scar;
(f) an inflammatory disease, disorder, or condition in the vessel/blood selected from Behcet's disease, vasculitis, sepsis, tumor angiogenesis, proliferative vascular disease and restenosis;
(g) an inflammatory disease, disorder, or condition in the eye selected from conjunctivitis, scleritis, episcleritis, panuveitis, choroiditis, chorioretinitis, neuroretinitis, uveitis, orbital inflammatory disease, and optical neuritis;
(h) an inflammatory disease, disorder, or condition in the central or peripheral nervous system selected from non-viral and viral encephalitis and meningitis, depression, neuropathic pain, traumatic brain injury, Myelitis, Charcot-Marie-Tooth disease type 1, Amyotrophic lateral sclerosis (ALS), Creutzfeldt-Jakob disease, demyelinating polyneuropathy and peripheral neuropathy;
(i) an autoimmune disease, disorder, or condition selected from Lupus, Guillain-Barre syndrome, Myasthenia gravis, Hashimoto's thyroiditis, idiopathic purpura, aplastic anemia, Graves disease, and Myocarditis;
(k) an inflammatory disease, disorder, or condition in the reproductive system selected from endometriosis, uterine fibroma, prostate dysplasia or growth, and cervix dysplasia; and
(l) an inflammatory disease, disorder, or condition in the bone and/or joints selected from juvenile idiopathic arthritis, psoriatic arthritis, periodontitis, and hand, foot, ankle, knee, hip, shoulder, elbow or spine arthritis and/or demineralization.

### Claim 2

A method for treating an inflammatory disease, disorder or condition comprising administering to a patient suffering from the inflammatory disease, disorder or condition a compound of formula (IV):
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 ortho, meta or para relative to Z;
each R is independently hydrogen, halogen, —CN, hydroxyl, (C1-C3)fluoroalkyl, (C1-C3)fluoroalkoxy, (C3-C6)cycloalkyl, —NO2, —NR1R2, (C1-C4)alkoxy, phenoxy, —NR1—SO2—NR1R2, —NR1—SO2—R1, —NR1—C(═O)—R1, —NR1—C(═O)—NR1R2, —SO2—NR1R2, —SO3H, —O—SO2—OR3, —O—P(═O)—(OR3)(OR4), —O—CH2—COOR3, (C1-C3)alkyl, the alkyl being optionally mono- or di-substituted by a hydroxyl group or a group of formula (IIa):
or a group of formula (IIIa):
each of R1 and R2 is independently hydrogen or (C1-C3)alkyl;
each of R3 and R4 is independently hydrogen, Li+, Na+, K+, N+ (Ra)4 or benzyl;
n is 1, 2 or 3;
n′ is 1, 2 or 3;
each R′ is independently hydrogen, (C1-C3)alkyl, hydroxyl, halogen, —NO2, —NR1R2, morpholinyl, morpholino, N-methylpiperazinyl, (C1-C3)fluoroalkyl, (C1-C4)alkoxy, —O—P(═O)—(OR3)(OR4), —CN, a —NH—SO2—N(CH3)2 group, a group of formula (IIa):
or a group of formula (IIIa):
A is a covalent bond, oxygen, or NH;
B is a covalent bond or NH;
m is 1, 2, 3, 4 or 5;
p is 1, 2 or 3;
each of Ra and Rb is independently hydrogen, (C1-C5)alkyl, or (C3-C6)cycloalkyl, or Ra and Rb form together with the nitrogen atom to which Ra and Rb are attached a saturated 5- or 6-membered heterocycle, the heterocycle optionally containing a further heteroatom chosen among N, O, S, the heterocycle being optionally substituted by one or more Ra, provided that when R′ is a group (IIa) or (IIIa), n′ may be 2 or 3 only if other R′ groups are different from the group (IIa) or (IIIa); and
R″ is hydrogen, (C1-C4)alkyl, or a group of formula (IIa) as defined herein,
wherein the inflammatory disease, disorder or condition being treated by the administration of the compound of formula (IV) is selected from the group consisting of:
(a) an inflammatory disease, disorder, or condition in the pancreas selected from diabetes type-1, diabetes type-2, acute and chronic pancreatitis;
(b) an inflammatory disease, disorder, or condition in the kidney selected from glomerulosclerosis, glomerulonephritis, nephritis, acute kidney injury, Berger's disease, Goodpasture's syndrome, Wegener's granulomatosis and kidney transplant acute or chronic rejection;
(c) an inflammatory disease, disorder, or condition in the liver selected from nonalcoholic steatohepatitis (NASH), non-alcoholic fatty liver disease (NAFLD), cholestatic liver disease, sclerosing cholangitis and liver transplant acute or chronic rejection;
(d) an inflammatory disease, disorder, or condition in the lung or heart selected from chronic obstructive pulmonary disease (COPD), pulmonary fibrosis, pulmonary hypertension, sarcoidosis, myocarditis, pericarditis and lung or heart transplant acute or chronic rejection;
(e) an inflammatory disease, disorder, or condition in the skin selected from contact dermatitits, atopic dermatitis, alopecia areata, erythema multiforma, dermatitis herpetiformis, scleroderma, vitiligo, hypersensitivity angiitis, urticaria, bullous pemphigoid, pemphigus vulgaris, pemphigus foliaceus, paraneoplastic pemphigus, epidermolysis bullosa acquisita, acnea and keloid scar;
(f) an inflammatory disease, disorder, or condition in the vessel/blood selected from Behcet's disease, vasculitis, sepsis, tumor angiogenesis, proliferative vascular disease and restenosis;
(g) an inflammatory disease, disorder, or condition in the eye selected from conjunctivitis, scleritis, episcleritis, panuveitis, choroiditis, chorioretinitis, neuroretinitis, uveitis, orbital inflammatory disease, and optical neuritis;
(h) an inflammatory disease, disorder, or condition in the central or peripheral nervous system selected from non-viral and viral encephalitis and meningitis, depression, neuropathic pain, traumatic brain injury, Myelitis, Charcot-Marie-Tooth disease type 1, Amyotrophic lateral sclerosis (ALS), Creutzfeldt-Jakob disease, demyelinating polyneuropathy and peripheral neuropathy;
(i) an autoimmune disease, disorder, or condition selected from Lupus, Guillain-Barre syndrome, Myasthenia gravis, Hashimoto's thyroiditis, idiopathic purpura, aplastic anemia, Graves disease, and Myocarditis;
(k) an inflammatory disease, disorder, or condition in the reproductive system selected from endometriosis, uterine fibroma, prostate dysplasia or growth, and cervix dysplasia; and
(l) an inflammatory disease, disorder, or condition in the bone and/or joints selected from juvenile idiopathic arthritis, psoriatic arthritis, periodontitis, and hand, foot, ankle, knee, hip, shoulder, elbow or spine arthritis and/or demineralization.

### Claim 3 (depends on 2)

The method according to claim 2, wherein the compound is of formula (IVb):
or a pharmaceutically acceptable salt thereof.

### Claim 4 (depends on 2)

The method according to claim 2, wherein the compound is of formula (IVb′):
or a pharmaceutically acceptable salt thereof.

### Claim 5 (depends on 2)

The method according to claim 2, wherein the compound is
or a pharmaceutically acceptable salt thereof.

### Claim 6 (depends on 1)

The method according to claim 1, wherein the inflammatory disease, disorder or condition is in the liver and is selected from nonalcoholic steatohepatitis (NASH), non-alcoholic fatty liver disease (NAFLD), cholestatic liver disease, sclerosing cholangitis and liver transplant acute or chronic rejection.

### Claim 7 (depends on 1)

The method according to claim 1, wherein the inflammatory disease, disorder or condition is in the lung or heart and is selected from chronic obstructive pulmonary disease (COPD), pulmonary fibrosis, pulmonary hypertension, sarcoidosis, myocarditis, pericarditis and lung or heart transplant acute or chronic rejection.

### Claim 8 (depends on 1)

The method according to claim 1, further comprising measuring a level of the 8-Chloro-N-(4-(trifluoromethoxy)phenyl)quinolin-2-amine or the pharmaceutically acceptable salt thereof, in a blood, plasma, tissue, saliva, and/or serum sample of the patient.

### Claim 9 (depends on 1)

The method according to claim 1, wherein a presence and/or expression level of miR-124 in a blood and/or tissue sample of the patient is measured prior to and after administering the 8-Chloro-N-(4-(trifluoromethoxy)phenyl)quinolin-2-amine or the pharmaceutically acceptable thereof to the patient.

### Claim 10 (depends on 1)

The method according to claim 1, further comprising monitoring a severity of the inflammatory disease, disorder, or condition or monitoring efficacy of the 8-Chloro-N-(4-(trifluoromethoxy)phenyl)quinolin-2-amine or the pharmaceutically acceptable salt thereof in treating the inflammatory, disease, disorder, or condition in the patient, the monitoring including using an algorithm that combines an miR-124 level and the level of a cytokine or another biomarker, or the level of the 8-Chloro-N-(4-(trifluoromethoxy)phenyl)quinolin-2-amine or the pharmaceutically acceptable salt thereof.

### Claim 11

A method for treating an inflammatory disease, disorder or condition comprising administering to a patient suffering from the inflammatory disease, disorder or condition a compound of Formula (I):
or a metabolite 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 ortho, meta or para relative to Z;
each R is independently hydrogen, halogen, —CN, hydroxyl, (C1-C3)fluoroalkyl, (C1-C3)fluoroalkoxy, (C3-C6)cycloalkyl, —NO2, —NR1R2, (C1-C4)alkoxy, phenoxy, —NR1—SO2—NR1R2, —NR1—SO2—R1, —NR1—C(═O)—R1, —NR1—C(═O)—NR1R2, —SO2—NR1R2, —SO3H, —O—SO2—OR3, —O—P(═O)—(OR3)(OR4), —O—CH2—COOR3, (C1-C3)alkyl, the alkyl being optionally mono- or di-substituted by a hydroxyl group, a group of formula (IIa):
or a group of formula (IIIa):
Q is N or O, provided that R″ does not exist when Q is O;
each of R1 and R2 is independently hydrogen or (C1-C3)alkyl;
each of R3 and R4 is independently hydrogen, Li+, Na+, K+, N+(Ra)4 or benzyl;
n is 1, 2 or 3;
n′ is 1, 2 or 3;
each R′ is independently hydrogen, (C1-C3)alkyl, hydroxyl, halogen, —NO2, —NR1R2, morpholinyl, morpholino, N-methylpiperazinyl, (C1-C3)fluoroalkyl, (C1-C4)alkoxy, —O—P(═O)—(OR3)(OR4), —CN, a —NH—SO2—N(CH3)2 group, a group of formula (IIa):
or a group of formula (IIIa):
A is a covalent bond, oxygen, or NH;
B is a covalent bond or NH;
m is 1, 2, 3, 4 or 5;
p is 1, 2 or 3;
each of Ra and Rb is independently hydrogen, (C1-C5)alkyl, or (C3-C6)cycloalkyl, or Ra and Rb form together with the nitrogen atom to which Ra and Rb are attached a saturated 5- or 6-membered heterocycle, the heterocycle optionally containing a further heteroatom chosen among N, O, S, the heterocycle being optionally substituted by one or more Ra, provided that when R′ is a group (IIa) or (IIIa), n′ may be 2 or 3 only if other R′ groups are different from the group (IIa) or (IIIa); and
wherein the compound of formula (I) is administered together with one or more JAK-inhibitor, and
wherein the inflammatory disease, disorder or condition being treated by the administration of the compound of formula (I) is selected from the group consisting of:
(a) an inflammatory disease, disorder, or condition in the pancreas selected from diabetes type-1, diabetes type-2, acute and chronic pancreatitis;
(b) an inflammatory disease, disorder, or condition in the kidney selected from glomerulosclerosis, glomerulonephritis, nephritis, acute kidney injury, Berger's disease, Goodpasture's syndrome, Wegener's granulomatosis and kidney transplant acute or chronic rejection;
(c) an inflammatory disease, disorder or condition in the liver selected from nonalcoholic steatohepatitis (NASH), non-alcoholic fatty liver disease (NAFLD), cholestatic liver disease, sclerosing cholangitis and liver transplant acute or chronic rejection;
(d) an inflammatory disease, disorder, or condition in the lung or heart selected from chronic obstructive pulmonary disease (COPD), pulmonary fibrosis, pulmonary hypertension, sarcoidosis, myocarditis, pericarditis and lung or heart transplant acute or chronic rejection;
(e) an inflammatory disease, disorder, or condition in the skin selected from contact dermatitis, atopic dermatitis, alopecia areata, erythema multiforma, dermatitis herpetiformis, scleroderma, vitiligo, hypersensitivity angiitis, urticaria, bullous pemphigoid, pemphigus vulgaris, pemphigus foliaceus, paraneoplastic pemphigus, epidermolysis bullosa acquisita, acnea and keloid scar;
(f) an inflammatory disease, disorder, or condition in the vessel/blood selected from Behcet's disease, vasculitis, sepsis, tumor angiogenesis, proliferative vascular disease and restenosis;
(g) an inflammatory disease, disorder, or condition in the eye selected from conjunctivitis, scleritis, episcleritis, panuveitis, choroiditis, chorioretinitis, neuroretinitis, uveitis, orbital inflammatory disease, and optical neuritis;
(h) an inflammatory disease, disorder, or condition in the central or peripheral nervous system selected from non-viral and viral encephalitis and meningitis, depression, neuropathic pain, traumatic brain injury, Myelitis, Charcot-Marie-Tooth disease type 1, Amyotrophic lateral sclerosis (ALS), Creutzfeldt-Jakob disease, demyelinating polyneuropathy and peripheral neuropathy;
(i) an autoimmune disease, disorder, or condition selected from Lupus, Guillain-Barre syndrome, Myasthenia gravis, Hashimoto's thyroiditis, idiopathic purpura, aplastic anemia, Graves disease, and Myocarditis;
(k) an inflammatory disease, disorder, or condition in the reproductive system selected from endometriosis, uterine fibroma, prostate dysplasia or growth, and cervix dysplasia; and
(l) an inflammatory disease, disorder, or condition in the bone and/or joints selected from juvenile idiopathic arthritis, psoriatic arthritis, periodontitis, and hand, foot, ankle, knee, hip, shoulder, elbow or spine arthritis and/or demineralization.

### Claim 12 (depends on 11)

The method according to claim 11, wherein the compound of formula (I) is administered together with tofacitinib.

### Claim 13 (depends on 11)

The method according to claim 11, wherein the compound of formula (I) is a compound of formula (Ib):
or a metabolite or a pharmaceutically acceptable salt thereof and is administered together with one or more JAK-inhibitor.

### Claim 14 (depends on 11)

The method according to claim 11, wherein the compound of formula (I) is a compound of formula (Ib):
or a metabolite or pharmaceutically acceptable salt thereof and is administered together with tofacitinib.

### Claim 15 (depends on 2)

The method according to claim 2, wherein the compound of formula (IV) is administered together with one or more JAK-inhibitor.

### Claim 16 (depends on 2)

The method according to claim 2, wherein the compound of formula (IV) is administered together with tofacitinib.

### Claim 17 (depends on 4)

The method according to claim 4, wherein the compound of formula (IVb′) is
and is administered together with one or more JAK-inhibitor.

### Claim 18 (depends on 4)

The method according to claim 4, wherein the compound of formula (IVb′) is
and is administered together with tofacitinib.

### Claim 19

A pharmaceutical composition comprising
a compound of formula (I):
or a metabolite or a pharmaceutically acceptable salt thereof, and
one or more JAK-inhibitor,
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 ortho, meta or para relative to Z;
each R is independently hydrogen, halogen, —CN, hydroxyl, (C1-C3)fluoroalkyl, (C1-C3)fluoroalkoxy, (C3-C6)cycloalkyl, —NO2, —NR1R2, (C1-C4)alkoxy, phenoxy, —NR1—SO2—NR1R2, —NR1—SO2—R1, —NR1—C(═O)—R1, —NR1—C(═O)—NR1R2, —SO2—NR1R2, —SO3H, —O—SO2—OR3, —O—P(═O)—(OR3)(OR4), —O—CH2—COOR3, (C1-C3)alkyl, the alkyl being optionally mono- or di-substituted by a hydroxyl group or a group of formula (IIa):
or a group of formula (IIIa):
Q is N or O, provided that R″ does not exist when Q is O;
each of R1 and R2 is independently hydrogen or (C1-C3)alkyl;
each of R3 and R4 is independently hydrogen, Li+, Na+, K+, N+ (Ra)4 or benzyl;
n is 1, 2 or 3;
n′ is 1, 2 or 3;
each R′ is independently hydrogen, (C1-C3)alkyl, hydroxyl, halogen, —NO2, —NR1R2, morpholinyl, morpholino, N-methylpiperazinyl, (C1-C3)fluoroalkyl, (C1-C4)alkoxy, —O—P(═O)—(OR3)(OR4), —CN, a —NH—SO2—N(CH3)2 group, a group of formula (IIa):
or a group of formula (IIIa):
A is a covalent bond, oxygen, or NH;
B is a covalent bond or NH;
m is 1, 2, 3, 4 or 5;
p is 1, 2 or 3;
each of Ra and Rb is independently hydrogen, (C1-C5)alkyl, or (C3-C6)cycloalkyl, or Ra and Rb form together with the nitrogen atom to which Ra and Rb are attached a saturated 5- or 6-membered heterocycle, the heterocycle optionally containing a further heteroatom chosen among N, O, S, the heterocycle being optionally substituted by one or more Ra, provided that when R′ is a group (IIa) or (IIIa), n′ may be 2 or 3 only if other R′ groups are different from the group (IIa) or (IIIa); and
R″ is hydrogen, (C1-C4)alkyl, or a group of formula (IIa) as defined herein.

### Claim 20 (depends on 19)

The pharmaceutical composition according to claim 19, wherein the one or more JAK-inhibitor includes tofacitinib.

### Claim 21 (depends on 19)

The pharmaceutical composition according to claim 19, wherein the compound is of formula (Ib′):
or a metabolite or a pharmaceutically acceptable salt thereof.

### Claim 22 (depends on 19)

The pharmaceutical composition according to claim 19, wherein:
the compound of formula (I) is 8-Chloro-N-(4-(trifluoromethoxy)phenyl)quinolin-2-amine, and
the one or more JAK-inhibitor is tofacitinib.

### Claim 23

A pharmaceutical composition comprising
a compound of formula (IV):
or a pharmaceutically acceptable salt thereof, and
one or more JAK-inhibitor,
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 ortho, meta or para relative to Z;
each R is independently hydrogen, halogen, —CN, hydroxyl, (C1-C3)fluoroalkyl, (C1-C3)fluoroalkoxy, (C3-C6)cycloalkyl, —NO2, —NR1R2, (C1-C4)alkoxy, phenoxy, —NR1—SO2—NR1R2, —NR1—SO2—R1, —NR1—C(═O)—R1, —NR1—C(═O)—NR1R2, —SO2—NR1R2, —SO3H, —O—SO2—OR3, —O—P(═O)—(OR3)(OR4), —O—CH2—COOR3, (C1-C3)alkyl, the alkyl being optionally mono- or di-substituted by a hydroxyl group or a group of formula (IIa):
or a group of formula (IIIa):
each of R1 and R2 is independently hydrogen or (C1-C3)alkyl;
each of R3 and R4 is independently hydrogen, Li+, Na+, K+, N+ (Ra)4 or benzyl;
n is 1, 2 or 3;
n′ is 1, 2 or 3;
each R′ is independently hydrogen, (C1-C3)alkyl, hydroxyl, halogen, —NO2, —NR1R2, morpholinyl, morpholino, N-methylpiperazinyl, (C1-C3)fluoroalkyl, (C1-C4)alkoxy, —O—P(═O)—(OR3)(OR4), —CN, a —NH—SO2—N(CH3)2 group, a group of formula (IIa):
or a group of formula (IIIa):
A is a covalent bond, oxygen, or NH;
B is a covalent bond or NH;
m is 1, 2, 3, 4 or 5;
p is 1, 2 or 3;
each of Ra and Rb is independently hydrogen, (C1-C5)alkyl, or (C3-C6)cycloalkyl, or Ra and Rb form together with the nitrogen atom to which Ra and Rb are attached a saturated 5- or 6-membered heterocycle, the heterocycle optionally containing a further heteroatom chosen among N, O, S, the heterocycle being optionally substituted by one or more Ra, provided that when R′ is a group (IIa) or (IIIa), n′ may be 2 or 3 only if other R′ groups are different from the group (IIa) or (IIIa); and
R″ is hydrogen, (C1-C4)alkyl, or a group of formula (IIa) as defined herein.

### Claim 24 (depends on 23)

The pharmaceutical composition according to claim 23, wherein the one or more JAK-inhibitor includes tofacitinib.

### Claim 25 (depends on 23)

The pharmaceutical composition according to claim 23, wherein the compound is:

### Claim 26 (depends on 25)

The pharmaceutical composition according to claim 25, wherein the one or more JAK-inhibitor includes tofacitinib.

### Claim 27 (depends on 11)

The method according to claim 11, wherein the compound of formula (I) is a compound of formula (Ib′):
or a metabolite or a pharmaceutically acceptable salt thereof, and is administered together with one or more JAK-inhibitor.

### Claim 28 (depends on 11)

The method according to claim 11, wherein the compound of formula (I) is a compound of formula (Ib′):
or a metabolite or a pharmaceutically acceptable salt thereof, and is administered together with tofacitinib.

### Claim 29 (depends on 11)

The method according to claim 11, wherein the compound of formula (I) is chosen among:
or a metabolite or a pharmaceutically acceptable salt thereof, and
is administered together with one or more JAK-inhibitor.

### Claim 30 (depends on 11)

The method according to claim 11, wherein the compound of formula (I) is chosen among:
or a metabolite or a pharmaceutically acceptable salt thereof, and
is administered together with tofacitinib.

### Claim 31 (depends on 11)

The method according to claim 11, wherein the compound of formula (I) is 8-Chloro-N-(4-(trifluoromethoxy)phenyl)quinolin-2-amine and is administered together with one or more JAK-inhibitor.

### Claim 32 (depends on 11)

The method according to claim 11, wherein the compound of formula (I) is 8-Chloro-N-(4-(trifluoromethoxy)phenyl)quinolin-2-amine and is administered together with tofacitinib.

### Claim 33 (depends on 19)

The pharmaceutical composition according to claim 19, wherein the compound is of formula (Ib):
or a metabolite or a pharmaceutically acceptable salt thereof.

### Claim 34 (depends on 19)

The pharmaceutical composition according to claim 19, wherein the compound is of formula (Ib):
or a metabolite or a pharmaceutically acceptable salt thereof, and the one or more JAK-inhibitor includes tofacitinib.

### Claim 35 (depends on 19)

The pharmaceutical composition according to claim 19, wherein the compound is of formula (Ib′):
or a metabolite or a pharmaceutically acceptable salt thereof, and the one or more JAK-inhibitor includes tofacitinib.

### Claim 36 (depends on 19)

The pharmaceutical composition according to claim 19, wherein the compound of formula (I) is 8-Chloro-N-(4-(trifluoromethoxy)phenyl)quinolin-2-amine.

### Claim 37 (depends on 19)

The pharmaceutical composition according to claim 19, wherein the compound of formula (I) is chosen among:
or a metabolite or a pharmaceutically acceptable salt thereof.

### Claim 38 (depends on 19)

The pharmaceutical composition according to claim 19, wherein the compound of formula (I) is chosen among:
or a metabolite or a pharmaceutically acceptable salt thereof, and
the one or more JAK-inhibitor includes tofacitinib.