Enzyme activated self-immolative n-substituted nitrogen mustard prodrugs

US7235585B2 · kind B2 · utility

Assignee

• Cancer Research Technology Limited · GB

Inventors

• Caroline Joy Springer · London, GB
• Ion Niculescu-Duvaz · Bucharest, RO
• Dan Niculescu-Duvaz · Sutton, GB

Key dates

• Filing date: Sep 1, 2003
• Grant date: Jun 26, 2007
• Expiry date: Sep 22, 2023

Classification

• Technology area (CPC C): Chemistry; Metallurgy
• CPC primary: C07C275/32
• WIPO field: Pharmaceuticals
• WIPO sector: Chemistry

Abstract

This invention pertains to certain enzyme (CPG2) activated self-immolative nitrogen mustard prodrugs, which are useful in enzyme prodrug therapy (EPT), such as ADEPT and GDEPT, for the treatment of proliferative conditions, such as cancer, and which have the following formula:wherein: RN is independently C1-7alkyl; X1 is independently —I, —Br, or —Cl; X2 is independently —I, —Br, or —Cl; the group —N(CH2CH2X1)(CH2CH2X2) is independently attached at the 2-position or at the 4-position; each RG is independently —H or an ester substituent; n is independently an integer from 0 to 4; each RP, if present, is independently a phenyl substituent; m is independently an integer from 0 to 4; each RM, if present, is independently a mustard substituent; and pharmaceutically acceptable salts, solvates, amides, and esters thereof. The present invention also pertains to pharmaceutical compositions comprising such compounds; such compounds and compositions for use in methods of treatment of the human or animal body by therapy; the use of such compounds and compositions for the manufacture of medicaments for the treatment of proliferative conditions; and the like.