SUBSTITUTED 2-HYDROXY-4-(2-(PHENYLSULFONAMIDO)ACETAMIDO)BENZOIC ACID ANALOGS AS INHIBITORS OF STAT PROTEIN

摘要

In one aspect, the invention relates to substituted 2-hydroxy-4-(2-(phenylsulfonamido)acetamido)benzoic acid analogs, derivatives thereof, and related compounds, which are useful as inhibitors of STAT protein activity; synthetic methods for making the compounds; pharmaceutical compositions comprising the compounds; and methods of treating disorders of uncontrolled cellular proliferation associated with a STAT protein activity dysfunction using the compounds and compositions. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.

主权项

1. A compound having a structure represented by a formula: wherein each of m and n is independently an integer from 0-3; wherein R1 is selected from A1, A2, -(A1)-(A2), -(A2)-(A3), -(A3)-(A2), -(A3)-(A4), -(A5)-(A1)-(A7), -(A5)-(A2)-(A8), -(A5)-(A3)-(A7), and -(A5)-(A6)-L-(A7); wherein A1 is C3-C6 cycloalkyl, and substituted with 0-3 groups selected from halo, hydroxyl, amino, nitro, cyano, C1-C6 haloalkyl, C1-C6 polyhaloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, C1-C6 polyhaloalkoxy, C1-C6 alkylthio, C1-C6 haloalkythio, C1-C6 polyhaloalkylthio, C1-C6 alkylamino, C1-C6 dialkylamino, (C1-C6)-alk-(C1-C6)-alkoxy, (C1-C6)-alk-(C1-C6)-haloalkoxy, (C1-C6)-alk-(C1-C6)-polyhaloalkoxy, (C1-C6)-alk-(C1-C6)-alkylthio, (C1-C6)-alk-(C1-C6)-haloalkythio, (C1-C6)-alk-(C1-C6)-polyhaloalkylthio, CO2H, (C═O)R4, (C═O)OR4, and (C═O)NHR4; wherein A2 is C3-C6 heterocycloalkyl, and substituted with 0-3 groups selected from halo, hydroxyl, amino, nitro, cyano, C1-C6 haloalkyl, C1-C6 polyhaloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, C1-C6 polyhaloalkoxy, C1-C6 alkylthio, C1-C6 haloalkythio, C1-C6 polyhaloalkylthio, C1-C6 alkylamino, C1-C6 dialkylamino, (C1-C6)-alk-(C1-C6)-alkoxy, (C1-C6)-alk-(C1-C6)-haloalkoxy, (C1-C6)-alk-(C1-C6)-polyhaloalkoxy, (C1-C6)-alk-(C1-C6)-alkylthio, (C1-C6)-alk-(C1-C6)-haloalkythio, (C1-C6)-alk-(C1-C6)-polyhaloalkylthio, CO2H, (C═O)R5, (C═O)OR5, and (C═O)NHR5; wherein A3 is aryl, and substituted with 0-3 groups selected from halo, hydroxyl, amino, nitro, cyano, C1-C6 haloalkyl, C1-C6 polyhaloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, C1-C6 polyhaloalkoxy, C1-C6 alkylthio, C1-C6 haloalkythio, C1-C6 polyhaloalkylthio, C1-C6 alkylamino, C1-C6 dialkylamino, (C1-C6)-alk-(C1-C6)-alkoxy, (C1-C6)-alk-(C1-C6)-haloalkoxy, (C1-C6)-alk-(C1-C6)-polyhaloalkoxy, (C1-C6)-alk-(C1-C6)-alkylthio, (C1-C6)-alk-(C1-C6)-haloalkythio, (C1-C6)-alk-(C1-C6)-polyhaloalkylthio, CO2H, (C═O)R6, (C═O)OR6, and (C═O)NHR6; wherein A4 is aryl, and substituted with 1-3 groups selected from halo, hydroxyl, amino, nitro, cyano, C1-C6 haloalkyl, C1-C6 polyhaloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, C1-C6 polyhaloalkoxy, C1-C6 alkylthio, C1-C6 haloalkythio, C1-C6 polyhaloalkylthio, C1-C6 alkylamino, C1-C6 dialkylamino, (C1-C6)-alk-(C1-C6)-alkoxy, (C1-C6)-alk-(C1-C6)-haloalkoxy, (C1-C6)-alk-(C1-C6)-polyhaloalkoxy, (C1-C6)-alk-(C1-C6)-alkylthio, (C1-C6)-alk-(C1-C6)-haloalkythio, (C1-C6)-alk-(C1-C6)-polyhaloalkylthio, CO2H, (C═O)R7, (C═O)OR7, and (C═O)NHR7; wherein A5 is selected from C3-C6 cycloalkyl, C3-C6 heterocycloalkyl, and aryl, and substituted with 0-3 groups selected from halo, hydroxyl, amino, nitro, cyano, C1-C6 haloalkyl, C1-C6 polyhaloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, C1-C6 polyhaloalkoxy, C1-C6 alkylthio, C1-C6 haloalkythio, C1-C6 polyhaloalkylthio, C1-C6 alkylamino, C1-C6 dialkylamino, (C1-C6)-alk-(C1-C6)-alkoxy, (C1-C6)-alk-(C1-C6)-haloalkoxy, (C1-C6)-alk-(C1-C6)-polyhaloalkoxy, (C1-C6)-alk-(C1-C6)-alkylthio, (C1-C6)-alk-(C1-C6)-haloalkythio, (C1-C6)-alk-(C1-C6)-polyhaloalkylthio, CO2H, (C═O)R8, (C═O)OR8, and (C═O)NHR8; wherein A6 is selected from C3-C6 cycloalkyl, C3-C6 heterocycloalkyl, and aryl, and substituted with 0-3 groups selected from halo, hydroxyl, amino, nitro, cyano, C1-C6 haloalkyl, C1-C6 polyhaloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, C1-C6 polyhaloalkoxy, C1-C6 alkylthio, C1-C6 haloalkythio, C1-C6 polyhaloalkylthio, C1-C6 alkylamino, C1-C6 dialkylamino, (C1-C6)-alk-(C1-C6)-alkoxy, (C1-C6)-alk-(C1-C6)-haloalkoxy, (C1-C6)-alk-(C1-C6)-polyhaloalkoxy, (C1-C6)-alk-(C1-C6)-alkylthio, (C1-C6)-alk-(C1-C6)-haloalkythio, (C1-C6)-alk-(C1-C6)-polyhaloalkylthio, CO2H, (C═O)R9, (C═O)OR9, and (C═O)NHR9; wherein A7 is selected from C3-C6 cycloalkyl, C3-C6 heterocycloalkyl, and aryl, and substituted with 0-3 groups selected from halo, hydroxyl, amino, nitro, cyano, C1-C6 haloalkyl, C1-C6 polyhaloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, C1-C6 polyhaloalkoxy, C1-C6 alkylthio, C1-C6 haloalkythio, C1-C6 polyhaloalkylthio, C1-C6 alkylamino, C1-C6 dialkylamino, (C1-C6)-alk-(C1-C6)-alkoxy, (C1-C6)-alk-(C1-C6)-haloalkoxy, (C1-C6)-alk-(C1-C6)-polyhaloalkoxy, (C1-C6)-alk-(C1-C6)-alkylthio, (C1-C6)-alk-(C1-C6)-haloalkythio, (C1-C6)-alk-(C1-C6)-polyhaloalkylthio, CO2H, (C═O)R10, (C═O)OR10, and (C═O)NHR10; wherein A8 is selected from C3-C6 cycloalkyl, C3-C6 heterocycloalkyl, and aryl, and substituted with 0-3 groups selected from halo, hydroxyl, amino, nitro, C1-C6 haloalkyl, C1-C6 polyhaloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, C1-C6 polyhaloalkoxy, C1-C6 alkylthio, C1-C6 haloalkythio, C1-C6 polyhaloalkylthio, C1-C6 alkylamino, C1-C6 dialkylamino, (C1-C6)-alk-(C1-C6)-alkoxy, (C1-C6)-alk-(C1-C6)-haloalkoxy, (C1-C6)-alk-(C1-C6)-polyhaloalkoxy, (C1-C6)-alk-(C1-C6)-alkylthio, (C1-C6)-alk-(C1-C6)-haloalkythio, (C1-C6)-alk-(C1-C6)-polyhaloalkylthio, CO2H, (C═O)R11, (C═O)OR11, and (C═O)NHR11; wherein L is selected from —(C═O)— and —SO2—; wherein R2 is selected from C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 haloalkyl, C2-C6 haloalkenyl, C2-C6 haloalkynyl, C1-C6 polyhaloalkyl, C2-C6 polyhaloalkenyl, C2-C6 polyhaloalkynyl; or wherein R2 is aryl substituted with 0-5 groups independently selected from halo, hydroxyl, amino, nitro, cyano, C1-C6 haloalkyl, C1-C6 polyhaloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, C1-C6 polyhaloalkoxy, C1-C6 alkylthio, C1-C6 haloalkythio, C1-C6 polyhaloalkylthio, C1-C6 alkylamino, C1-C6 dialkylamino, (C1-C6)-alk-(C1-C6)-alkoxy, (C1-C6)-alk-(C1-C6)-haloalkoxy, (C1-C6)-alk-(C1-C6)-polyhaloalkoxy, (C1-C6)-alk-(C1-C6)-alkylthio, (C1-C6)-alk-(C1-C6)-haloalkythio, (C1-C6)-alk-(C1-C6)-polyhaloalkylthio, CO2H, (C═O)OR11, and (C═O)NHR11; wherein R3 is aryl substituted with 0-5 groups independently selected from halo, hydroxyl, amino, nitro, cyano, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 polyhaloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, C1-C6 polyhaloalkoxy, C1-C6 alkylamino, C1-C6 dialkylamino, (C1-C6)-alk-(C1-C6)-alkoxy, (C1-C6)-alk-(C1-C6)-haloalkoxy, and (C1-C6)-alk-(C1-C6)-polyhaloalkoxy; and wherein each of R4, R5, R6, R7, R8, R9, R10, and R11 is independently selected from hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, and C1-C6 polyhaloalkyl; or a pharmaceutically acceptable salt, hydrate, solvate, or polymorph thereof.