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TETRAHYDRO-SPIROINDOLINE-PYRROLOPYRROLE-TRIONES INHIBITORS OF THE NRF2-BETA-TRCP INTERACTION FOR USE IN THE TREATMENT OF NRF2-RELATED DISEASESCM Patents

[0000] The present invention relates to NRF2-βTrCP interaction inhibitors with general formula I and its derivate salts for use in the treatment of NRF2-related diseases caused by chronic inflammation and oxidative stress. More specifically the present invention relates to NRF2-βTrCP interaction inhibitors with specific formula I and its derivate salts for treating diseases of the liver related with chronic inflammation and oxidative stress, such as fatty liver disease.

Datos clave

CategoríaInvención

Índice de la ficha

Updated at
05/11/2026
Numero publicacion
EP.4029500.A1
Fecha publicacion
20/07/2022
Anio publicacion
2022

En detalle

Reivindicaciones

1. An NRF2-βTrCP interaction inhibitor, characterized by Formula (I) or its derivative salts, <img class="EMIRef" id="88dfc1ec-01fd-4881-8816-06a716751154-ib0003" /> wherein: • n can be 0 or 1, • R1 can be O<2>CCH<3> or a six-membered ring for forming a benzodioxane, benzomethylenedioxy, or naphthalene substituent; • R2 can be H or a six-membered ring for forming a benzodioxane, benzomethylenedioxy, or naphthalene substituent; • R3 can be H or CH<3>; • R4 can be H or CH<3>; and • R5 can be H, Cl, or CH<3>. for use in the treatment of NRF2-related diseases. 2. The NRF2-βTrCP interaction inhibitor for use according to claim 1, wherein the inhibitor is characterized by Formula (II), <img class="EMIRef" id="88dfc1ec-01fd-4881-8816-06a716751154-ib0004" /> <img class="EMIRef" id="88dfc1ec-01fd-4881-8816-06a716751154-ib0005" /> or its derivative salts. 3. The NRF2-βTrCP interaction inhibitor for use according to any of the preceding claims, in the treatment of an NRF2-related disease caused by inflammation and oxidative stress. 4. The NRF2-βTrCP interaction inhibitor for use according to any of the preceding claims, in the treatment of a disease caused by Gram-negative bacterial infection. 5. A pharmaceutical composition comprising the NRF2-βTrCP interaction inhibitor of Formula I or II, or derivative salts thereof, and optionally pharmaceutically acceptable vehicles or excipients, for use in the treatment of NRF2-related diseases. 6. The pharmaceutical composition for use according to claim 5, in the treatment of NRF2-related diseases caused by inflammation and oxidative stress. 7. The pharmaceutical composition for use according to any of claims 5 or 6, in the treatment of a disease caused by Gram-negative bacterial infection. 8. An in vitro method for identifying and producing compounds for the treatment of NRF2-related diseases, which comprises: a) determining if the inhibition of NRF2-βTrCP interaction by the candidate compound has taken place, and b) wherein if said inhibition has taken place, it is indicative of the selected compound being effective in the treatment of NRF2-related diseases. 9. The in vitro method for identifying and producing compounds according to claim 8, for the treatment of NRF2-related diseases caused by inflammation and oxidative stress, which comprises: a) determining if the inhibition of NRF2-βTrCP interaction by the candidate compound has taken place, and b) wherein if said inhibition has taken place, it is indicative of the selected compound being effective in the treatment of NRF2-related diseases caused by inflammation and oxidative stress. 10. The in vitro method for identifying and producing compounds according to claims 8 or 9, for the treatment of a disease caused by Gram-negative bacterial infection, which comprises: a) determining if the inhibition of NRF2-βTrCP interaction by the candidate compound has taken place, and b) wherein if said inhibition has taken place, it is indicative of the selected compound being effective in the treatment of a disease caused by Gram-negative bacterial infection.

Etiquetas

Inventores
Cuadrado Pastor AntonioCUADRADO PASTOR, AntonioFERNÁNDEZ GINÉS, RaquelFernández Ginés RaquelEncinar José AntonioENCINAR, José AntonioLeón Martínez RafaelLEÓN MARTÍNEZ, RafaelFRANCO GONZÁLEZ, Juan FelipeFranco González Juan FelipeGarcía López ManuelaGARCÍA LÓPEZ, ManuelaRODRÍGUEZ FRANCO, María IsabelRodríguez Franco María IsabelROJO SANCHÍS, Ana IsabelRojo Sanchís Ana IsabelFernandez Gines RaquelFERNANDEZ GINES, RaquelLEON MARTINEZ, RafaelLeon Martinez RafaelFranco Gonzalez Juan FelipeFRANCO GONZALEZ, Juan FelipeGARCIA LOPEZ, ManuelaGarcia Lopez ManuelaRodriguez Franco María IsabelRODRIGUEZ FRANCO, María IsabelRojo Sanchis Ana IsabelROJO SANCHIS, Ana Isabelクアドラド パストル,アントニオフェルナンデス ギネス,ラケルエンシナル,ホセ アントニオレオン マルティネス,ラファエルフランコ ゴンザレス,フアン フェリペガルシア ロペス,マヌエラロドリゲス フランコ,マリア イサベルロホ サンチス,アナ イサベルCuadrado Pastor, AntonioFernandez Gines, RaquelEncinar, Jose AntonioEncinar Jose AntonioLeon Martinez, RafaelFranco Gonzalez, Juan FelipeGarcia Lopez, ManuelaRodriguez Franco Maria IsabeRodriguez Franco, Maria IsabeRojo Sanchis, Ana IsabelRodriguez Franco Maria Isabel
Solicitantes
Universidad Autónoma de MadridConsejo Superior de Investigaciones CientíficasUniversidad Miguel Hernández de ElcheFundación para la Investigación Biomédica del Hospital Universitario de La Princesa
Clasificacion ipc
A61K 31/ 404 A IA61K 31/ 407 A IA61P 25/ 14 A IA61P 31/ 04 A IA61P 35/ 00 A IA61P 1/ 16 A IC07D 487/ 20 A IG01N 33/ 50 A I
Clasificacion cpc
4C086/AA014C086/AA024C086/CB034C086/GA164C086/MA014C086/MA044C086/NA144C086/ZA75A61K31/407A61P1/16
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