298211-16-2

Upstream product

• 111-42-2 2,2'-iminobis[ethanol] 
• 134227-45-5 3,4,5-trifluorobenzonitrile 

Downstream Products

• 694503-98-5 3,5-difluoro-4-[bis(2-tetrahydropyranyloxyethyl)amino]benzoyl azide 
• 694503-97-4 3,5-difluoro-4-[bis(2-tetrahydropyranyloxyethyl)amino]benzoic acid 
• 298211-19-5 2-{4-[bis-(2-methanesulfonyloxy-ethyl)-amino]-3,5-difluoro-benzoylamino}-pentanedioic acid di-tert-butyl ester 
• 298211-08-2 di-tert-butyl (3,5-difluoro-4-[bis(2-iodoethyl)amino]benzoyl)-L-glutamate 
• 298211-10-6 di-tert-butyl {4-[bis(2-bromoethyl)amino]-3,5-difluorobenzoyl}-L-glutamate 
• 298211-18-4 2-{4-[bis-(2-hydroxy-ethyl)-amino]-3,5-difluoro-benzoylamino}-pentanedioic acid di-tert-butyl ester 
• 298211-09-3 di-tert-butyl {4-[bis(2-chloroethyl)amino]-3,5-difluorobenzoyl}-L-glutamate 
• 298211-17-3 3,5-difluoro-4-[bis(2-hydroxyethyl)amino]benzoic acid 

Relevant academic research and scientific papers

NITROGEN MUSTARD COMPOUNDS AND PRODRUGS THEREFOR

This invention pertains to nitrogen mustard compounds (Formula (II)) and prodrugs therefor (Formula (I)), methods for their preparation, pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, both in vitro a

Novel fluorinated prodrugs for activation by carboxypeptidase G2 showing good in vivo antitumor activity in gene-directed enzyme prodrug therapy

Sixteen novel polyfluorinated benzoic acid mustards have been synthesized for use in gene-directed enzyme prodrug therapy (GDEPT). Eight of these were benzoic acid L-glutamate mustards for evaluation as prodrugs and the other eight were the active drugs formed by the action of the bacterial enzyme carboxypeptidase G2 (CPG2). All of the di- and trifluorinated prodrugs were efficiently cleaved by the enzyme. In contrast, the tetrafluorinated prodrugs were found to be competitive inhibitors of CPG2, the first such inhibitors to have been described. The di- and trifluorinated prodrugs were differentially cytotoxic to human breast carcinoma cells (MDA MB 361) expressing CPG2, compared to control cells that did not express the enzyme. The difluorinated prodrug {4-[bis(2-bromoethyl)amino]-3,5-difluorobenzoyl}-L-glutamic acid and its iodoethylamino analogue were effective substrates for the enzyme and showed excellent therapeutic activity in CPG2-expressing MDA MB 361 xenografts, either curing or greatly inhibiting tumor growth and extending the life of the animals.

Significant Differences in Biological Parameters between Prodrugs Cleavable by Carboxypeptidase G2 That Generate 3,5-Difluoro-phenol and -aniline Nitrogen Mustards in Gene-Directed Enzyme Prodrug Therapy Systems

Nine new nitrogen mustard compounds derived from 2,6-difluoro-4-hydroxy- (3a-e) and 2,6-difluoro-4-amino- (4a-d) aniline were synthesized as potential prodrugs. They were designed to be activated to their corresponding 3,5-difluorophenol and -aniline (4)-