Tumor protease activated prodrugs of phosphoramide mustard analo

Organic compounds -- part of the class 532-570 series – Organic compounds – Phosphorus esters

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558169, 558170, 558171, 514114, 514118, 514137, 514553, 514603, 562 67, 564 85, 564 94, C07F 902, A61K 3166

Patent

active

056590610

ABSTRACT:
The composition, synthesis, and applications of tumor associated protease activated prodrugs of phosphoramide mustard, isophosphoramide mustard and analogs with detoxification functionalities are described. These drugs release a cytotoxic phosphoramide mustard analog following activation by tumor associated proteases and esterases. The general structure for these drugs is: ##STR1## Wherein R1 is a beta-X-ethyl-amino group which may optionally bear substituents on the nitrogen or carbon atoms; wherein X is a good leaving group such as a halogen; R2 is a beta-X-ethyl-amino group which may optionally bear substituents on the nitrogen or carbon atoms; or an amino group (NH.sub.2) which may optionally be substituted. Wherein A is a benzyloxy derivative with one or more acyloxy or acylamino groups in para or ortho portions relative to the phosphoester; and wherein the acyloxy or acylamino groups are not (substituted or unsubstituted) p-guanidino-benzoyloxy groups or p-guanidino-benzoylamino groups.

REFERENCES:
patent: 5274162 (1993-12-01), Glazier

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