Patent ID: 8273787
Filing Date: 2012-09-25
Classification: A61K,C07D

Abstract:
1. An activated cytotoxic compound for attachment to a targeting molecule for the treatment of proliferative disorders comprising, an activator, a spacer linker, a linker, and a cytotoxic drug wherein the linker is a self-immolative linker is para-Aminobenzyl Alcohol (PABA), 3,3-Dimethyl-4-hydroxybutyric Acid, an Ethylenediamine, γ-Aminobutyric Acid (GABA), 2-Hydroxycinnamic Acid, “Trimethyl Lock”, or an Ethanolamine and the spacer linker comprises Glutaryl, Diglycoyl, Succinyl, Homophthalyl, or Amino-PEG-Acid; wherein the activated cytotoxic drug is (E)-2,4,6-trimethoxystyryl-4-methoxy-3-aminobenzylsulfone (ON 01500); (E)-5-((2,4,6-trimethoxystyrylsulfonyl)methyl)-2-methoxyphenol (ON 013100); and or (E)-2,4,6-trimethoxystyryl-4-methoxy-3-aminophenylsulfonamide (ON 24160); and wherein the activator is N-Hydroxysuccinimidyl, N-Hydroxyphthalimideyl, o-Nitrophenyl, Acyl azide, p-Nitrophenyl, N-Hydroxybenzotriazoleyl, Pentachlorophenyl, Pentafluorophenyl, or 2,4,6-trichlorophenyl.