TAK1 KINASE INHIBITORS, COMPOSITIONS, AND USED RELATED THERETO

摘要

The disclosure relates to TAK1 inhibitors, compositions, and uses related thereto. In certain embodiments, the disclosure relates to compounds of formula (I), pharmaceutical compositions having a compound of formula (I), and methods of treating or preventing cancer by administering an effective amount of a pharmaceutical composition having a compound of formula (I) to a subject in need thereof.;

主权项

1. A compound of formula I, or salt or prodrug thereof wherein - - - is a single bond with a trans isomer to R2 and a cis isomer to —(C═O)R1, a cis isomer to R2 and a cis isomer to —(C═O)R1; or a trans isomer to R2 and a trans isomer to —(C═O)R1; R1 is hydrogen, hydroxy, alkyl, alkoxy, carbocyclyl, aryl, or heterocyclyl, wherein R1 is optionally substituted with one or more, the same or different, R10; R2 is formyl, carboxy, carbamoyl, or phosphonate, wherein R2 is optionally substituted with one or more, the same or different, R10; R3 is nitro, cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, alkylamino, (alkyl)2-amino, alkylsulfinyl, alkylsulfonyl, arylsulfonyl, aryl, or heteroaryl wherein R3 is optionally substituted with one or more, the same or different, R10; R4 is hydrogen or R3 and R4 and the attached atoms form an aryl or heteroaryl ring wherein the ring is optionally substituted with one or more, the same or different, R10; R10 is alkyl, halogen, nitro, cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, alkoxy, alkylthio, alkylamino, (alkyl)2-amino, alkylsulfinyl, alkylsulfonyl, arylsulfonyl, carbocyclyl, aryl, or heterocyclyl, wherein R10 is optionally substituted with one or more, the same or different, R11; R11 is alkyl, halogen, nitro, cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, alkoxy, alkylthio, alkylamino, (alkyl)2-amino, alkylsulfinyl, alkylsulfonyl, arylsulfonyl, carbocyclyl, aryl, or heterocyclyl, wherein R11 is optionally substituted with one or more, the same or different, R12; R12 is alkyl, halogen, nitro, cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, alkoxy, alkylthio, alkylamino, (alkyl)2-amino, alkylsulfinyl, alkylsulfonyl, arylsulfonyl, carbocyclyl, aryl, or heterocyclyl, wherein R12 is optionally substituted with one or more, the same or different, R13; and R13 is halogen, nitro, cyano, hydroxy, trifluoromethoxy, trifluoromethyl, amino, formyl, carboxy, carbamoyl, mercapto, sulfamoyl, methyl, ethyl, methoxy, ethoxy, acetyl, acetoxy, methylamino, ethylamino, dimethylamino, diethylamino, N-methyl-N-ethylamino, acetylamino, N-methylcarbamoyl, N-ethylcarbamoyl, N,N-dimethylcarbamoyl, N,N-diethylcarbamoyl, N-methyl-N-ethylcarbamoyl, methylthio, ethylthio, methylsulfinyl, ethylsulfinyl, mesyl, ethylsulfonyl, methoxycarbonyl, ethoxycarbonyl, N-methylsulfamoyl, N-ethylsulfamoyl, N,N-dimethylsulfamoyl, N,N-diethylsulfamoyl, N-methyl-N-ethylsulfamoyl, carbocyclyl, aryl, or heterocyclyl.