STAT3 INHIBITORS AND THEIR ANTICANCER USE

摘要

In one aspect, the invention relates to substituted 6-amino-5,8-dioxo-5,8-dihydronaphthalene-1-sulfonamide analogs and derivatives thereof, substituted 4-amino-5H-naphtho[1,8-cd]isothiazol-5-one 1,1-dioxide analogs and 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 R1 is selected from hydrogen and C1-C3 alkyl; wherein Q1 is —NR2aR2b and wherein Q2 is O; or wherein Q1 and Q2 are together N;
wherein each of R2a and R2b, when present, is independently selected from hydrogen and C1-C3 alkyl; wherein Q3 is selected from —(C1-C6)-Ar1, Ar1, —(C1-C6)-Cy1, and Cy1;
wherein Ar1, when present, is selected from phenyl, naphthyl, monocyclic heteroaryl, and bicyclic heteroaryl; and wherein Ar1 is substituted with 0, 1, 2, or 3 groups independently selected from halogen, —CN, —OH, —NH2, —NO2, C1-C6 alkyl, C1-C6 monohaloalkyl, C1-C6 polyhaloalkyl, C1-C6 hydroxyalkyl, C1-C6 monoalkylamino, C1-C6 dialkylamino, —(C1-C6)NR4aR4b, —(C1-C6)-(C═O)R3, —(C1-C6)-(C═O)OR3, —(C1-C6)-(C═O)NR4aR4b, —(C1-C6)-Ar2, Ar2, —(C1-C6)-Cy2, Cy2, and —S(O)nNR5aR5b;wherein n is 0, 1, or 2;wherein each R3, when present, is independently selected from hydrogen, C1-C6 alkyl, C1-C6 monohaloalkyl, C1-C6 polyhaloalkyl, C1-C6 hydroxyalkyl, and C1-C6 aminoalkyl;wherein each of R4a and R4b, when present, is independently selected from hydrogen, C1-C6 alkyl, C1-C6 monohaloalkyl, C1-C6 polyhaloalkyl, C1-C6 hydroxyalkyl, and C1-C6 aminoalkyl;wherein each of R5a and R5b, when present, is independently selected from hydrogen, C1-C6 alkyl, C1-C6 monohaloalkyl, C1-C6 polyhaloalkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, and —(C═O)NR6aR6b;
wherein each of R6a and R6b, when present, is independently selected from hydrogen and C1-C6 alkyl;wherein each Ar2, when present, is independently selected from is phenyl and monocyclic heteroaryl; and wherein Ar2 is substituted with 0, 1, 2, or 3 groups independently selected from halogen, —CN, —OH, —NH2, —NO2, C1-C6 alkyl, C1-C6 monohaloalkyl, C1-C6 polyhaloalkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C1-C6 monoalkylamino, and C1-C6 dialkylamino;wherein each Cy2, when present, is independently selected from C3-C8 cycloalkyl and C2-C7 heterocycloalkyl; and wherein Cy2 is substituted with 0, 1, 2, or 3 groups independently selected from halogen, —CN, —OH, —NH2, —NO2, C1-C6 alkyl, C1-C6 monohaloalkyl, C1-C6 polyhaloalkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C1-C6 monoalkylamino, C1-C6 dialkylamino, —(C═O)R7, —(C═O)OR7, —(C═O)NR8aR8b, —(C═O)—(C1-C6 alkyl)Ar3, —(C═O)—O—(C1-C6 alkyl)Ar3, and —(C═O)—NR8a—(C1-C6 alkyl)Ar3;
wherein each R7, when present, is independently selected from hydrogen, C1-C6 alkyl, C1-C6 monohaloalkyl, and C1-C6 polyhaloalkyl;wherein each of R8a and R8b, when present, is independently selected from hydrogen, C1-C6 alkyl, C1-C6 monohaloalkyl, and C1-C6 polyhaloalkyl;wherein each Ar3, when present, is independently selected from phenyl and monocyclic heteroaryl substituted with 0, 1, 2, or 3 groups independently selected from halogen, —CN, —OH, —NH2, —NO2, C1-C6 alkyl, C1-C6 monohaloalkyl, and C1-C6 polyhaloalkyl; wherein Cy1, when present, is selected from C3-C8 cycloalkyl and C2-C7 heterocycloalkyl; and wherein Cy2 is substituted with 0, 1, 2, or 3 groups independently selected from halogen, —CN, —OH, —NH2, —NO2, C1-C6 alkyl, C1-C6 monohaloalkyl, C1-C6 polyhaloalkyl, C1-C6 hydroxyalkyl, C1-C6 monoalkylamino, C1-C6 dialkylamino, —(C1-C6)NR4aR4b, —(C1-C6)-(C═O)R3, —(C1-C6)-(C═O)OR3, —(C1-C6)-(C═O)NR4aR4b, —(C1-C6)-Ar2, Ar2, —(C1-C6)-Cy2, Cy2, and —S(O)nNR5aR5b; or a pharmaceutically acceptable salt, solvate, or polymorph thereof.