Inhibitors of protein tyrosine kinase activity and use thereof to treat ophthalmic disorders

• Main Authors: VAISBURG ARKADII, GAUDETTE FREDERIC, CLARIDGE STEPHEN WILLIAM, ZHAN LIJIE, RAEPPEL STEPHANE, RAEPPEL FRANCK
• Format: Patent
• Language: English
• Published: 26.09.2014
• Subjects: CHEMISTRY; HETEROCYCLIC COMPOUNDS; HUMAN NECESSITIES; HYGIENE; MEDICAL OR VETERINARY SCIENCE; METALLURGY; ORGANIC CHEMISTRY; PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES; SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS ORMEDICINAL PREPARATIONS

Disclosed are thieno[3,2-b]pyridine derivatives selected from 3-[(6-(7-(4-(3-cyclopropylureido)-2-fluorophenoxy)thieno[3,2-b]pyridin-2-yl)pyridin-3-yl)methyl]-1-ethyl-3-[2-methoxyethyl]urea, N-((6-(7-(4-(3-cyclopropylureido)-2-fluorophenoxy)thieno[3,2-b]pyridin-2-yl)pyridin-3-yI)methyl)-N-(2-methoxyethyl)formamide, N-((6-(7-(4-(3-cyclopropylureido)-2,3-difluorophenoxy)thieno[3,2-b]pyridin-2-yl)-pyridin-3-yl)methyl)-N-(2-methoxyethyl)acetamide, 1-cyclopropyI-3-(3-fluoro-4-(2-(5-((4-(2-hydroxyacetyl)piperazin-1-yl)methyl)pyridin-2-yl)thieno[3,2-b]pyridin-7-yloxy)phenyl)urea, (S)-2-(4-((6-(7-(4-(3-cyclopropylureido)-2-fluorophenoxy)thieno[3,2-b]pyridin-2-yl)pyridin-3-yl)methyl)piperazin-1-yl)-2-oxoethyl 2-amino-3-methylbutanoate, 1-cyclopropyl-3-(3-fluoro-4-(2-(5-((2-(methylsulfonyl)ethylamino)methyl)pyridin-2-yl)thieno[3,2-b ]pyridin-7-yloxy)phenyl)urea, 1-cyclopropyl-3-(3-fluoro-4-(2-(1-(2-((2-hydroxyethyl)(methyl)amino)ethyl)-1H-pyrazol-4-yl)thieno[3,2-b]pyridin-7-yloxy)phenyl)urea, 1-((2-(7-(4-Isopropylaminocarbonylamino-2-fluorophenoxy)thieno[3,2-b ]pyridin-2-yl)-1-methyl-1H-imidazol-5-yl)methyl)-3-isopropyl-1-(2-methoxyethyl)urea, N-((2-(7-(4-(3-cyclopropylureido)-2-fluorophenoxy)thieno[3,2-b]pyridin-2-yl)-1-methyl-1H-imidazol-5-yl)methyl)-2-hydroxy-N-(2-methoxyethyl)acetamide, 1-cyclopropyl-3-(3-fluoro-4-(2-(5-(4-(4-methylpiperazin-1-yl)piperidine-1-carbonyl)pyridin-2-yl)thieno[3,2-b]pyridin-7-yloxy)phenyl)urea and 1-cyclopropyl-3-(3-fluoro-4-(2-(1-(2-morpholinoethyl)-1H-imidazol-4-yl)thieno[3,2-b]pyridin-7-yloxy)phenyl)urea. Further disclosed is a composition comprising a compound as defined above and a pharmaceutically acceptable carrier, for treating an ophthalmic disease, condition or disorder, wherein the ophthalmic disease, disorder or condition is selected from the group consisting of (a) a disease, disorder or condition caused by choroidal angiogenesis (including age-related macular degeneration), (b) diabetic retinopathy and (c) retinal edema.