DERIVADOS DE INDOLINA-CARBOXAMIDA CON ACTIVIDAD SOBRE LOS CANALES SODIO

• Main Authors: BESIDSKI YEVGENI, ARVIDSSON PER I, NILSSON LINDA I, AHLIN KRISTOFER
• Format: Patent
• Language: Spanish
• Published: 28.01.2010
• 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

REFERIDA A UN COMPUESTO DERIVADO INDOLINA-CARBOXAMIDA DE FORMULA (I), DONDE R1 ES H, CN, ALQUILO C1-C3, HALO, ENTRE OTROS; m ES 1, 2 O 3; R2 Y R3 SON H, HALOALQUILO C1-C4, HALOALCOXI C1-C4, ENTRE OTROS; L1 ES ALQUILENO C1-C4, PENTILENO O CICLOALQUILENO C3-C6, OPCIONALMENTE SUSTITUIDOS CON X4; R2 Y R3 NO PUEDESN SER AMBOS H; X4 ES F, ALQUILO C1-C3, CICLOALQUILO C3-C7, ENTRE OTROS; L2 ES ALQUILENO C1-C3 OPCIONALMENTE SUSTITUIDO CON UNO O MAS X4. SON COMPUESTOS PREFERIDOS: 2-(2-CIANOETIL)-3-OXO-N-(4-(TRIFLUOROMETOXI)BENCIL)ISOINDOLINA-1-CARBOXAMIDA, 2-(2-CIANOETIL)-N-(2-METIL-4-(TRIFLUOROMETOXI)BENCIL)-3-OXOISOINDOLINA-1-CARBOXAMIDA, 2-(3-CIANO-3-METILBUTIL)-3-OXO-N-(4-(TRIFLUOROMETOXI)BENCIL)ISOINDOLINA-1-CARBOXAMIDA, ENTRE OTROS. TAMBIEN ESTA REFERIDA A UNA COMPOSICION FARMACEUTICA. DICHOS COMPUESTOS TIENEN ACTIVIDAD SOBRE LOS CANALES DE SODIO NaV1.7 Y SON UTILES EN EL TRATAMIENTO DEL DOLOR TAL COMO DOLOR AGUDO, FIBROMIALGIA, ANGINA, ENTRE OTROS Compounds of formula I are claimed, wherein R1 is hydrogen, C1_3alkyl, C1_3alkoxy, cyano, hydroxy or halo; and wherein said C1-3alkyl is optionally substituted by one or more substituents independently selected from hydroxy, C1_3alkoxy andfluoro; and said C1_3alkoxy is optionally substituted by one or more fluoro; m is 1, 2 or 3; R2 and R3 is each and independently selected from hydrogen, C1-4haloalkyl, C1-4haloalkoxy, halo, C1-4alkoxy, C1-4alkyl and C3_7Cycloalkyloxy; wherein said C3_7cycloalkyloxy is optionally substituted by one or more fluoro; and R2 and R3 may not both be hydrogen; L1 is C1-4alkylene, pentylene, or C3-6 cycloalkylene, wherein said C1-4alkylene, pentylene or C3-6 cycloalkylene may be optionally substituted by one or more X4; X4 is fluoro, C1_3alkyl, C3_7Cycloalkyl, C1_3alkylOCi_3alkyl, C1_3alkoxy, cyano, hydroxy, R4O(C=O)-, R4NR5(C=O)-, R4O(C=O)NR5-, R4NR5(C=O)NR5-, R4(C=O)O-, R4(C=O)NR5-, R4NR5(C=O)O-, R4NR5(C=O)NR5-, C5-6 heteroaryl(C=O), or C5-6 heteroaryl; R4 is C1-4 alkylOC1-4 alkyl, C5-6 cycloalkyl, aryl, or aryl-C1-2 alkyl; R5 is H or methyl; and wherein said C1-3 alkylOC1-3alkyl, C1-3alkoxy and C1-4alkylsulfonyl is optionally substituted by one or more fluoro; L2 is C1-3 alkylene, optionally substituted by one or more X4; as well as pharmaceutically acceptable salt, or isomer thereof, or a salt of said isomer. Compounds of the invention are useful in therapy, such as pain therapy.