Pt(IV) chemotherapeutic prodrug and controlled release thereof for treatment of tumors

A Pt(IV) complex of formula (I), which is used as a prodrug activated by radiation for the treatment of a tumor,

• wherein L1 to L6 are ligands of platinum;
• the complex can release L5 and L6 to obtain a Pt(II) complex of formula (II) after irradiation,
• wherein the Pt(II) complex of formula (II) is Cisplatin, Carboplatin, Nedaplatin, Oxaliplatin, Lobaplatin, or Heptaplatin, wherein,
• (i)
• L5 is −O—C(O)—R, wherein R is each independently selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, nonyl, decyl, undecyl, dodecyl, tridecyl, tetradecyl, pentadecyl, hexadecyl, heptadecanyl, octadecyl, nonadecanyl, eicosyl;
• L6 is −O—C(O)—R, wherein R is each independently selected from (dimethylamino) methylene, 2-(dimethylamino) ethylene, 3-(dimethylamino) propylene, 4-(dimethylamino) butylene, 5-(dimethylamino) pentylene, 6-(dimethylamino) hexylene, 3-(4-iodophenyl) propylene, 3-(3-iodophenyl) propylene, 3-(3,5-diiodophenyl) propylene, 3-(4-bromophenyl) propylene, 3-(3-bromophenyl) propylene, 3-(3,5-dibromophenyl) propylene, methylamino, ethylamino, propylamino, butylamino, amylamino, hexylamino, heptylamino, octylamino, nonylamino, decylamino, undecylamino, dodecylamino, tridecylamino, tetradecylamino, pentadecylamino, hexadecylamino, heptadecanylamino, and octadecylamino;
• or
• (ii)
• L5 is −O—C(O)—R, wherein R is each independently selected from carboxymethylene, 2-carboxyethylene, 3-carboxypropylene, 4-carboxybutylene, 5-carboxypentylene, 6-carboxyhexylene;
• L6 is −O—C(O)—R, wherein R is each independently selected from (dimethylamino) methylene, 2-(dimethylamino) ethylene, 3-(dimethylamino) propylene, 4-(dimethylamino) butylene, 5-(dimethylamino) pentylene, 6-(dimethylamino) hexylene, 5-maleimidopentylene, 6-maleimidohexylene, 7-maleimidoheptylene, 8-maleimidooctylene, 3-(4-iodophenyl) propylene, 3-(3-iodophenyl) propylene, 3-(3,5-diiodophenyl) propylene, 3-(4-bromophenyl) propylene, 3-(3-bromophenyl) propylene, 3-(3,5-dibromophenyl) propylene;
• or
• (iii)
• L5 is −O—C(O)—R, wherein R is each independently selected from (dimethylamino) methylene, 2-(dimethylamino) ethylene, 3-(dimethylamino) propylene, 4-(dimethylamino) butylene, 5-(dimethylamino) pentylene, 6-(dimethylamino) hexylene;
• L6 is −O—C(O)—R, wherein R is each independently selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, nonyl, decyl, undecyl, dodecyl, tridecyl, tetradecyl, pentadecyl, hexadecyl, heptadecanyl, octadecyl, nonadecanyl, eicosyl, carboxymethylene, 2-carboxyethylene, 3-carboxypropylene, 4-carboxybutylene, 5-carboxypentylene, 6-carboxyhexylene, (dimethylamino) methylene, 2-(dimethylamino) ethylene, 3-(dimethylamino) propylene, 4-(dimethylamino) butylene, 5-(dimethylamino) pentylene, 6-(dimethylamino) hexylene, 5-maleimidopentylene, 6-maleimidohexylene, 7-maleimidoheptylene, 8-maleimidooctylene, 3-(4-iodophenyl) propylene, 3-(3-iodophenyl) propylene, 3-(3,5-diiodophenyl) propylene, 3-(4-bromophenyl) propylene, 3-(3-bromophenyl) propylene, 3-(3,5-dibromophenyl) propylene, methylamino, ethylamino, propylamino, butylamino, amylamino, hexylamino, heptylamino, octylamino, nonylamino, decylamino, undecylamino, dodecylamino, tridecylamino, tetradecylamino, pentadecylamino, hexadecylamino, heptadecanylamino, and octadecylamino;
• or
• (iv)
• L5 is −O—C(O)—R, wherein R is each independently selected from 5-maleimidopentylene, 6-maleimidohexylene, 7-maleimidoheptylene, 8-maleimidooctylene;
• L6 is −O—C(O)—R, wherein R is each independently selected from carboxymethylene, 2-carboxyethylene, 3-carboxypropylene, 4-carboxybutylene, 5-carboxypentylene, 6-carboxyhexylene, (dimethylamino) methylene, 2-(dimethylamino) ethylene, 3-(dimethylamino) propylene, 4-(dimethylamino) butylene, 5-(dimethylamino) pentylene, 6-(dimethylamino) hexylene, 5-maleimidopentylene, 6-maleimidohexylene, 7-maleimidoheptylene, 8-maleimidooctylene, 3-(4-iodophenyl) propylene, 3-(3-iodophenyl) propylene, 3-(3,5-diiodophenyl) propylene, 3-(4-bromophenyl) propylene, 3-(3-bromophenyl) propylene, 3-(3,5-dibromophenyl) propylene, methylamino, propylamino, butylamino, amylamino, hexylamino, heptylamino, octylamino, nonylamino, decylamino, undecylamino, dodecylamino, tridecylamino, tetradecylamino, pentadecylamino, hexadecylamino, heptadecanylamino, and octadecylamino;
• or
• (v)
• L5 is −O—C(O)—R, wherein R is each independently selected from 3-(4-iodophenyl) propylene, 3-(3-iodophenyl) propylene, 3-(3,5-diiodophenyl) propylene, 3-(4-bromophenyl) propylene, 3-(3-bromophenyl) propylene, 3-(3,5-dibromophenyl) propylene;
• L6 is −O—C(O)—R, wherein R is each independently selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, nonyl, decyl, undecyl, dodecyl, tridecyl, tetradecyl, pentadecyl, hexadecyl, heptadecanyl, octadecyl, nonadecanyl, eicosyl, carboxymethylene, 2-carboxyethylene, 3-carboxypropylene, 4-carboxybutylene, 5-carboxypentylene, 6-carboxyhexylene, (dimethylamino) methylene, 2-(dimethylamino) ethylene, 3-(dimethylamino) propylene, 4-(dimethylamino) butylene, 5-(dimethylamino) pentylene, 6-(dimethylamino) hexylene, 5-maleimidopentylene, 6-maleimidohexylene, 7-maleimidoheptylene, 8-maleimidooctylene, 3-(4-iodophenyl) propylene, 3-(3-iodophenyl) propylene, 3-(3,5-diiodophenyl) propylene, 3-(4-bromophenyl) propylene, 3-(3-bromophenyl) propylene, 3-(3,5-dibromophenyl) propylene, methylamino, ethylamino, propylamino, butylamino, amylamino, hexylamino, heptylamino, octylamino, nonylamino, decylamino, undecylamino, dodecylamino, tridecylamino, tetradecylamino, pentadecylamino, hexadecylamino, heptadecanylamino, and octadecylamino;
• or
• (vi)
• L5 is-O—C(O)—R, wherein R is each independently selected from methylamino, ethylamino, propylamino, butylamino, amylamino, hexylamino, heptylamino, octylamino, nonylamino, decylamino, undecylamino, dodecylamino, tridecylamino, tetradecylamino, pentadecylamino, hexadecylamino, heptadecanylamino, and octadecylamino;
• L6 is −O—C(O)—R, wherein R is each independently selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, nonyl, decyl, undecyl, dodecyl, tridecyl, tetradecyl, pentadecyl, hexadecyl, heptadecanyl, octadecyl, nonadecanyl, eicosyl, (dimethylamino) methylene, 2-(dimethylamino) ethylene, 3-(dimethylamino) propylene, 4-(dimethylamino) butylene, 5-(dimethylamino) pentylene, 6-(dimethylamino) hexylene, 3-(4-iodophenyl) propylene, 3-(3-iodophenyl) propylene, 3-(3,5-diiodophenyl) propylene, 3-(4-bromophenyl) propylene, 3-(3-bromophenyl) propylene, 3-(3,5-dibromophenyl) propylene, methylamino, ethylamino, propylamino, butylamino, amylamino, hexylamino, heptylamino, octylamino, nonylamino, decylamino, undecylamino, dodecylamino, tridecylamino, tetradecylamino, pentadecylamino, hexadecylamino, heptadecanylamino, and octadecylamino.