ENZYME ACTIVATED SELF-IMMOLATIVE N-SUBSTITUTED NITROGEN MUSTARD PRODRUGS

• Main Authors: SPRINGER, CAROLINE JOY, NICULESCU-DUVAZ, ION, NICULESCU-DUVAZ, DAN M
• Format: Patent
• Language: English; French
• Published: 11.03.2004
• Edition: 7
• Subjects: ACYCLIC OR CARBOCYCLIC COMPOUNDS; CHEMISTRY; HUMAN NECESSITIES; HYGIENE; MEDICAL OR VETERINARY SCIENCE; METALLURGY; ORGANIC CHEMISTRY; PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES; SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS ORMEDICINAL PREPARATIONS

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 su ch compounds; such compounds and compositions for use in methods of treatment o f 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.