Texaphyrin-Pt(IV) conjugates and compositions for use in overcoming platinum resistance

A compound of the formula:

• wherein:
• R1 and R2 are each independently selected from hydrogen, halo, hydroxy, amino, mercapto, alkoxy(C<12), substituted alkoxy(C<12), and
• wherein n is 1-20 and R3 is hydrogen, alkyl(C≤6), substituted alkyl(C≤6), or a platinum (IV) chelating group;
• A1 and A2 are each independently selected from hydrogen, halo, hydroxy, alkyl(C≤12), substituted alkyl(C≤12), alkoxy(C<12), substituted alkoxy(C<12), and
• wherein n is 1-20 and R3 is hydrogen, alkyl(C≤6), substituted alkyl(C≤6), or a platinum (IV) chelating group;
• Y1, Y2, Y3, and Y4 are each independently selected from hydrogen, halo, alkyl(C≤12), and substituted alkyl(C≤12);
• X1, X2, X3, X4, X5, and X6 are each independently selected from hydrogen, hydroxy, halo, amino, carboxy, nitro, cyano,
• alkyl(C≤12), alkenyl(C≤12), aryl(C≤12), and a substituted version of any of these groups, or
• a platinum chelating group of the formula:
• -A3-X7-A4-R4, wherein A3 and A4 are each independently alkanediyl(C≤12), alkoxydiyl(C≤12), alkylaminodiyl(C≤12), or a substituted version of any of these groups, X7 is —NR5—, —C(O)NR5—, or —NR5C(O)—, wherein R5 is hydrogen, alkyl(C≤12), or substituted alkyl(C<12), and R4 is
• wherein:
• R6 is amino, or carboxy;
• L3, L4, and L6 are each ligands independently selected from aqua, ammonia, halide, or hydroxide, or
• L3 and L6 are taken together and are alkyldicarboxylate(C≤18), aryldicarboxylate(C≤18), or a substituted version of any either group;
• L5 is aqua, amino, nitrate, sulfate, halide, nitrate, sulfate, or hydroxide,
• alkylamine(C≤12), cycloalkylamine(C≤12), dialkylamine(C≤18), dicycloalkylamine(C≤18), arylamine(C≤12), diarylamine(C≤18), heteroarene(C≤12), alkylcarboxylate(C≤12), arylcarboxylate(C≤12), and a substituted version of any of these groups;
• L7 is amino or L4 and L7 are taken together and arc diaminocycloalkane(C≤12), or substituted diaminocycloalkane(C≤12);
• provided that at least one of X1, X2, X3, X4, X5, and X6 is a platinum (IV) chelating group;
• M is a trivalent lanthanide metal ion;
• and
• L1 and L2 are each anionic ligands independently selected from fluoride, chloride, bromide, perchlorate, nitrate, sulfate, trifluoromethylsulfonate, acetate, and trifluoroacetate;
• or a pharmaceutically acceptable salt thereof.