# US 8,273,882 B2 · Quinoxaline carboxamide derivatives as protein tyrosine kinase inhibitors > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 8,273,882 B2 - Document ID: US8273882B2 - Status: Granted - Kind: B2 - Application number: 12/470,191 - Filed: 2009-05-21 - Published: 2010-04-29 - Granted: 2012-09-25 - Earliest claimed: 2008-05-23 - Assignees: Novartis AG - Inventors: Pascal Furet; Diana Graus Porta; Vito Guagnano - Web page: https://patentgrep.com/patent/US8273882B2 ## CPC - A61K 31/4709: Non-condensed quinolines and containing further heterocyclic rings - A61K 31/496: Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin - A61K 31/498: Pyrazines or piperazines ortho- and peri-condensed with carbocyclic ring systems, e.g. quinoxaline, phenazine - A61K 31/506: not condensed and containing further heterocyclic rings - A61K 31/5377: not condensed and containing further heterocyclic rings, e.g. timolol - A61K 31/541: Non-condensed thiazines containing further heterocyclic rings - A61P 35/00: Antineoplastic agents - A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 - C07D 215/06: having only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, attached to the ring nitrogen atom - C07D 215/48: Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen - C07D 241/42: with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to carbon atoms of the hetero ring - C07D 401/04: directly linked by a ring-member-to-ring-member bond - C07D 401/12: linked by a chain containing hetero atoms as chain links - C07D 401/14: containing three or more hetero rings - C07D 403/12: linked by a chain containing hetero atoms as chain links - C07D 403/14: containing three or more hetero rings - C07D 409/14: containing three or more hetero rings - 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 - C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08) ## Abstract The invention relates to compounds of formula (I) wherein the substituents are as defined in the specification, in free form or in the form of a pharmaceutically acceptable salt, solvate, ester, N-oxide thereof; processes for the preparation thereof; to pharmaceuticals containing such compounds, in particular for the use in one or more Protein tyrosine kinase mediated diseases. ## Claims ### Claim 1 A compound selected from the group consisting of: 8-(2,6-Dichloro-3,5-dimethoxy-phenyl)-quinoxaline-5-carboxylic acid (4-dimethylaminomethyl-1H-imidazol-2-yl)-amide, 8-(2,6-Difluoro-3,5-dimethoxy-phenyl)-quinoxaline-5-carboxylic acid (4-dimethylaminomethyl-1H-imidazol-2-yl)-amide, 8-(2,6-Dichloro-3,5-dimethoxy-phenyl)-quinoxaline-5-carboxylic acid [5-(4-ethyl-piperazin-1-ylmethyl)-pyridin-2-yl]-amide, 8-(2,6-Difluoro-3,5-dimethoxy-phenyl)-quinoxaline-5-carboxylic acid [5-(4-ethyl-piperazin-1-ylmethyl)-pyridin-2-yl]-amide, 8-(2-Chloro-6-fluoro-3,5-dimethoxy-phenyl)-quinoxaline-5-carboxylic acid [5-(4-methyl-piperazin-1-ylmethyl)-pyridin-2-yl]-amide, and 8-(2-Chloro-6-fluoro-3,5-dimethoxy-phenyl)-quinoxaline-5-carboxylic acid (5-piperazin-1-ylmethyl-pyridin-2-yl)-amide, or a salt thereof. ### Claim 2 A compound 8-(2,6-Dichloro-3,5-dimethoxy-phenyl)-quinoxaline-5-carboxylic acid (4-dimethylaminomethyl-1H-imidazol-2-yl)-amide of formula or a salt thereof. ### Claim 3 A compound 8-(2,6-Dichloro-3,5-dimethoxy-phenyl)-quinoxaline-5-carboxylic acid (4-dimethylaminomethyl-1H-imidazol-2-yl)-amide of formula or a pharmaceutically acceptable salt thereof. ### Claim 4 A compound 8-(2,6-Dichloro-3,5-dimethoxy-phenyl)-quinoxaline-5-carboxylic acid (4-dimethylaminomethyl-1H-imidazol-2-yl)-amide of formula ### Claim 5 A compound 8-(2,6-Difluoro-3,5-dimethoxy-phenyl)-quinoxaline-5-carboxylic acid (4-dimethylaminomethyl-1H-imidazol-2-yl)-amide of formula or a salt thereof. ### Claim 6 A compound 8-(2,6-Difluoro-3,5-dimethoxy-phenyl)-quinoxaline-5-carboxylic acid (4-dimethylaminomethyl-1H-imidazol-2-yl)-amide of formula or a pharmaceutically acceptable salt thereof. ### Claim 7 A compound 8-(2,6-Difluoro-3,5-dimethoxy-phenyl)-quinoxaline-5-carboxylic acid (4-dimethylaminomethyl-1H-imidazol-2-yl)-amide of formula ### Claim 8 A compound 8-(2,6-Dichloro-3,5-dimethoxy-phenyl)-quinoxaline-5-carboxylic acid [5-(4-ethyl-piperazin-1-ylmethyl)-pyridin-2-yl]amide of formula or a salt thereof. ### Claim 9 A compound 8-(2,6-Dichloro-3,5-dimethoxy-phenyl)-quinoxaline-5-carboxylic acid [5-(4-ethyl-piperazin-1-ylmethyl)-pyridin-2-yl]amide of formula or a pharmaceutically acceptable salt thereof. ### Claim 10 A compound 8-(2,6-Dichloro-3,5-dimethoxy-phenyl)-quinoxaline-5-carboxylic acid [5-(4-ethyl-piperazin-1-ylmethyl)-pyridin-2-yl]amide of formula ### Claim 11 A compound 8-(2,6-Difluoro-3,5-dimethoxy-phenyl)-quinoxaline-5-carboxylic acid [5-(4-ethyl-piperazin-1-ylmethyl)-pyridin-2-yl]amide of formula or a salt thereof. ### Claim 12 A compound 8-(2,6-Difluoro-3,5-dimethoxy-phenyl)-quinoxaline-5-carboxylic acid [5-(4-ethyl-piperazin-1-ylmethyl)-pyridin-2-yl]amide of formula or a pharmaceutically acceptable salt thereof. ### Claim 13 A compound 8-(2,6-Difluoro-3,5-dimethoxy-phenyl)-quinoxaline-5-carboxylic acid [5-(4-ethyl-piperazin-1-ylmethyl)-pyridin-2-yl]amide of formula ### Claim 14 A compound 8-(2-Chloro-6-fluoro-3,5-dimethoxy-phenyl)-quinoxaline-5-carboxylic acid [5-(4-methyl-piperazin-1-ylmethyl)-pyridin-2-yl]amide of formula or a salt thereof. ### Claim 15 A compound 8-(2-Chloro-6-fluoro-3,5-dimethoxy-phenyl)-quinoxaline-5-carboxylic acid [5-(4-methyl-piperazin-1-ylmethyl)-pyridin-2-yl]amide of formula or a pharmaceutically acceptable salt thereof. ### Claim 16 A compound 8-(2-Chloro-6-fluoro-3,5-dimethoxy-phenyl)-quinoxaline-5-carboxylic acid [5-(4-methyl-piperazin-1-ylmethyl)-pyridin-2-yl]amide of formula ### Claim 17 A compound 8-(2-Chloro-6-fluoro-3,5-dimethoxy-phenyl)-quinoxaline-5-carboxylic acid (5-piperazin-1-ylmethyl-pyridin-2-yl)-amide of formula or a salt thereof. ### Claim 18 A compound 8-(2-Chloro-6-fluoro-3,5-dimethoxy-phenyl)-quinoxaline-5-carboxylic acid (5-piperazin-1-ylmethyl-pyridin-2-yl)-amide or of formula or a pharmaceutically acceptable salt thereof. ### Claim 19 A compound 8-(2-Chloro-6-fluoro-3,5-dimethoxy-phenyl)-quinoxaline-5-carboxylic acid (5-piperazin-1-ylmethyl-pyridin-2-yl)-amide of formula ### Claim 20 (depends on 3, 6, 9, 12, 15) A pharmaceutical composition comprising a compound, according to any one of claims 3, 6, 9, 12, 15, and 18, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier or diluent. ### Claim 21 (depends on 4, 7, 10, 13, 16) A pharmaceutical composition comprising a compound according to any one of claims 4, 7, 10, 13, 16, and 19 and a pharmaceutically acceptable carrier or diluent. ### Claim 22 A method of inhibiting FGFR kinase activity in a subject, wherein the method comprises administering to the subject an effective amount of a compound selected from the group consisting of: 8-(2,6-Dichloro-3,5-dimethoxy-phenyl)-quinoxaline-5-carboxylic acid (4-dimethylaminomethyl-1H-imidazol-2-yl)-amide, 8-(2,6-Difluoro-3,5-dimethoxy-phenyl)-quinoxaline-5-carboxylic acid (4-dimethylaminomethyl-1H-imidazol-2-yl)-amide, 8-(2,6-Dichloro-3,5-dimethoxy-phenyl)-quinoxaline-5-carboxylic acid [5-(4-ethyl-piperazin-1-ylmethyl)-pyridin-2-yl]-amide, 8-(2,6-Difluoro-3,5-dimethoxy-phenyl)-quinoxaline-5-carboxylic acid [5-(4-ethyl-piperazin-1-ylmethyl)-pyridin-2-yl]-amide, 8-(2-Chloro-6-fluoro-3,5-dimethoxy-phenyl)-quinoxaline-5-carboxylic acid [5-(4-methyl-piperazin-1-ylmethyl)-pyridin-2-yl]-amide, and 8-(2-Chloro-6-fluoro-3,5-dimethoxy-phenyl)-quinoxaline-5-carboxylic acid (5-piperazin-1-ylmethyl-pyridin-2-yl)-amide, or a pharmaceutically acceptable salt thereof.