4-(8-methoxy-1-((1-methoxypropan-2-yl)-2-(tetrahydro-2H-pyran-4-yl)-1H-imidazo[4,5-c]quinolin-7-yl)-3,5-dimethylisoxazole and its use as bromodomain inhibitor
Novel quinoline compounds pharmaceutical compositions containing such compounds and their use in therapy.
1. A method of treatment of an autoimmune or inflammatory condition in a human subject in need thereof which comprises administering a therapeutically effective amount of a compound of formula (I) which is 4-(8-methoxy-1-(1-methoxypropan-2-yl)-2-(tetrahydro-2H-pyran-4-yl)-1H-imidazo[4,5-c]quinolin-7-yl)-3,5-dimethylisoxazole
or a pharmaceutically acceptable salt thereof; wherein said autoimmune or inflammatory condition is selected from a group consisting of a chronic autoimmune or inflammatory condition, an acute inflammatory condition, a disease or condition which involves inflammatory responses to infections with bacteria, viruses, fungi, parasites, or their toxins, and a disease associated with systemic inflammatory response syndrome.
2. The method of claim 1 , wherein the compound of formula (I) is a compound of formula (IA) which is 4-(8-methoxy-1-((R)-1-methoxypropan-2-yl)-2-(tetrahydro-2H-pyran-4-yl)-1H-imidazo[4,5-c]quinolin-7-yl)-3,5-dimethylisoxazole
or a pharmaceutically acceptable salt thereof.
3. The method of claim 1 , wherein the compound of formula (I) is a compound of formula (IB) which is 4-(8-methoxy-1-((S)-1-methoxypropan-2-yl)-2-(tetrahydro-2H-pyran-4-yl)-1H-imidazo[4,5-c]quinolin-7-yl)-3,5-dimethylisoxazole
or a pharmaceutically acceptable salt thereof.
4. The method of claim 2 , wherein the compound is in the form of a methanesulfonate salt.
5. The method of claim 2 , wherein the compound is in the form of a free base.
6. The method of claim 2 , wherein the autoimmune or inflammatory condition is a chronic autoimmune or inflammatory condition.
7. The method of claim 6 , wherein the chronic autoimmune or inflammatory condition is selected from a group consisting of: rheumatoid arthritis, osteoarthritis, acute gout, psoriasis, systemic lupus erythematosus, multiple sclerosis, Crohn's disease, ulcerative colitis, asthma, chronic obstructive airways disease, pneumonitis, myocarditis, pericarditis, myositis, eczema, dermatitis, atopic dermatitis, alopecia, vitiligo, bullous skin diseases, nephritis, vasculitis, atherosclerosis, Alzheimer's disease, depression, Sjogren's syndrome, sialoadenitis, central retinal vein occlusion, branched retinal vein occlusion, Irvine-Gass syndrome, retinitis pigmentosa, pars planitis, birdshot retinochoroidopathy, epiretinal membrane, cystic macular edema, parafoveal telengiectasis, tractional maculopathies, vitreomacular traction syndromes, retinal detachment, neuroretinitis, idiopathic macular edema, retinitis, dry eye, vernal keratoconjunctivitis, atopic keratoconjunctivitis, uveitis, scleritis, diabetic retinopathy, diabetic macula edema, age-related macula dystrophy, hepatitis, pancreatitis, primary biliary cirrhosis, sclerosing cholangitis, Addison's disease, hypophysitis, thyroiditis, type I diabetes, and acute rejection of transplanted organs.
8. The method of claim 7 , wherein the chronic autoimmune or inflammatory condition is rheumatoid arthritis.
9. The method of claim 7 , wherein the chronic autoimmune or inflammatory condition is pancreatitis.
10. The method of claim 2 , wherein the autoimmune or inflammatory condition is an acute inflammatory condition.
11. The method of claim 10 , wherein the acute inflammatory condition is selected from a group consisiting of: acute gout, giant cell arteritis, nephritis, lupus nephritis, vasculitis with organ involvement, glomerulonephritis, vasculitis, giant cell arteritis, Wegener's granulomatosis, Polyarteritis nodosa, Behcet's disease, Kawasaki disease, Takayasu's arteritis, pyoderma gangrenosum, and acute rejection of transplanted organs.
12. The method of claim 2 , wherein the autoimmune or inflammatory condition is a disease or condition which involves inflammatory responses to infections with bacteria, viruses, fungi, parasites, or their toxins.
13. The method of claim 12 , wherein the disease or condition which involves inflammatory responses to infections with bacteria, viruses, fungi, parasites, or their toxins is selected from a group consisting of: sepsis, sepsis syndrome, septic shock, endotoxaemia, systemic inflammatory response syndrome, multi-organ dysfunction syndrome, toxic shock syndrome, acute lung injury, adult respiratory distress syndrome, acute renal failure, fulminant hepatitis, burns, acute pancreatitis, post-surgical syndromes, sarcoidosis, Herxheimer reactions, encephalitis, myelitis, meningitis, malaria, and systemic inflammatory response syndrome associated with influenza, herpes zoster, herpes simplex, or coronavirus.
14. The method of claim 13 , wherein the disease or condition which involves inflammatory responses to infections with bacteria, viruses, fungi, parasites, or their toxins is acute pancreatitis.
15. The method of claim 2 , wherein the autoimmune or inflammatory condition is a disease associated with systemic inflammatory response syndrome.
16. The method of claim 15 , wherein the disease associated with systemic inflammatory response syndrome is selected from a group consisting of:
sepsis, burns, pancreatitis, major trauma, haemorrhage, and ischaemia.