17794-35-3

Upstream product

• 2198-51-8 p-phenol 
• 6373-46-2 p-benzyloxyaniline 
• 100-39-0 benzyl bromide 
• 123-30-8 4-amino-phenol 
• 51388-20-6 4-benzyloxyaniline hydrochloride 
• 101582-69-8 4--O-benzylphenol 

Downstream Products

• 1204-69-9 4-[bis(2-chloroethyl)amino]phenol 
• 101596-02-5 Benzyl-<4-(N,N-bis-<2-brom-aethyl>-amino)-phenyl>-aether 
• 1457-06-3 4-[N,N-bis(2-chloroethyl)amino]phenol hydrochloride 
• 174579-29-4 Thiocarbonic acid O-{4-[bis-(2-chloro-ethyl)-amino]-phenyl} ester O-pentafluorophenyl ester 
• 209158-08-7 {2'-(3'',4''-dihydroxyphenyl)ethyl} carbamic acid p-(bis-2-chloroethylamino)phenyl ester 
• 209158-13-4 {2'-(4''-hydroxyphenyl)ethyl} carbamic acid p-(bis-2-chloroethylamino)phenyl ester 
• 371754-24-4 {2'-(4''-hydroxyphenoxy)ethylamine} carbamic acid p-(bis-2-chloroethylamino)phenyl ester 
• 371754-25-5 {2'-[(4''-hydroxyphenyl)thio]ethylamine} carbamic acid p-(bis-2-chloroethylamino)phenyl ester 
• 371754-20-0 3',4'-dihydroxybenzylamino-carbamic acid p-(bis-2-chloroethylamino)phenyl ester 
• 371754-15-3 (S)-[2'-amino-3'-(4''-hydroxyphenyl)propionic acid methyl ester]-carbamic acid p-(bis-2-chloroethylamino)phenyl ester 
• 371754-26-6 (S)-2-{4-[Bis-(2-chloro-ethyl)-amino]-phenoxythiocarbonylamino}-3-(4-hydroxy-phenyl)-propionic acid methyl ester 
• 371754-23-3 (R)-[1'-amino-2'-hydroxy-2'-(4''-hydroxyphenyl)propionic acid methyl ester]-carbamic acid p-(bis-2-chloroethylamino)phenyl ester 
• 156078-81-8 carbonic acid p-(bis-2-chloroethylamino)phenol ester-p-nitrophenyl ester 
• 180839-06-9 4-bis(2-chloroethyl)aminophenyl trimethylsilyl ether 

Relevant academic research and scientific papers

HYPOXIA ACTIVATED DRUGS OF NITROGEN MUSTARD ALKYLATORS

Hypoxia activated drug compounds having a structure of formula(I) are useful in the treatment of cancer and other hyperproliferative diseases.

Melanocyte-directed enzyme prodrug therapy (MDEPT): Development of second generation prodrugs for targeted treatment of malignant melanoma

Evaluation of second generation prodrugs for MDEPT, by oximetry, has highlighted structural properties that are advantageous and disadvantageous for efficient oxidation using mushroom tyrosinase. In particular, a sterically undemanding prodrug bis-(2-chlo

Melanocyte-directed enzyme prodrug therapy (MDEPT): Development of a targeted treatment for malignant melanoma

A novel prodrug rationally designed to function as a tyrosinase substrate has been synthesised to allow targeted treatment of malignant melanoma. This agent has been evaluated for tyrosinase-mediated drug release, and has been shown to act in the desired

Self-immolative nitrogen mustard prodrugs for suicide gene therapy

Four new potential self-immolative prodrugs derived from phenol and aniline nitrogen mustards, four model compounds derived from their corresponding fluoroethyl analogues and two new self-immolative linkers were designed and synthesized for use in the suicide gene therapy termed GDEPT (gene-directed enzyme prodrug therapy). The self-immolative prodrugs were designed to be activated by the enzyme carboxypeptidase G2 (CPG2) releasing an active drug by a 1,6-elimination mechanism via an unstable intermediate. Thus, N-[(4-{[4-(bis{2- chloroethyl}amino)phenoxycarbonyloxy]methyl}phenyl)carbamoyl]-L-glutamic acid (23), N-[(4-{[4(bis{2- chloroethyl}amino)phenoxycarbonyloxy]methyl}phenoxy)carbonyl]-L-glutamic acid (30), N-[(4-{N-(4-(bis[2- chloroethyl]amino}}pheny)carbamoyloxy]methyl}phenoxy)carbonyl]-L-glutmic acid (37), and N-[(4-{[N-(4-{bis[2- chloroethyl]amino}phenyl)carbamoyloxy]methyl}phenyl)carbamoyl]-L-glutamic acid (40) were synthesized. They are bifunctional alkylating agents in which the activating effects of the phenolic hydroxyl or amino functions are masked through an oxycarbonyl or a carbamoyl bond to a benzylic spacer which is itself]inked to a glutamic acid by an oxycarbonyl or a carbamoyl bond. The corresponding fluoroethyl compounds 25, 32, 42, and 44 were also synthesized. The rationale was to obtain model compounds with greatly reduced alkylating abilities that would be much less reactive with nucleophiles compared to the corresponding chloroethyl derivatives. This enabled studies of these model compounds as substrates for CPG2, without incurring the rapid and complicated decomposition pathways of the chloroethyl derivatives. The prodrugs were desired to be activated to their corresponding phenol and aniline nitrogen mustard drugs by CPG2 for use in GDEPT. The synthesis of the analogous novel parent drugs (21b, 51) is also described. A colorectal cell line was engineered to express CPG2 tethered to the outer cell surface. The phenylenediamine compounds were found to behave as prodrugs, yielding IC50 prodrug/IC50 drug ratios between 20- and 33-fold (for 37 and 40) and differentials of 12-14-fold between CPG2-expressing and control LacZ- expressing clones. The drugs released are up to 70-fold more potent than 4- [(2-chloroethyl)(2-mesyloxyethyl)amino]benzoic acid that results from the prodrug 4-[(2-chloroethyl)(2-mesyloxyethyl)amino]benzoyl-L-glutamic acid (CMBA) which has been used previously for GDEPT. These data demonstrate the viability of this strategy and indicate that self-immolative prodrugs can be synthesized to release potent mustard drugs selectively by cells expressing CPG2 tethered to the cell surface in GDEPT.

Glucuronide prodrugs of hydroxy compounds for antibody directed enzyme prodrug therapy (adept): A phenol nitrogen mustard carbamate

A prodrug consisting of a β-D-glucuronic acid linked to a self-immolative spacer (a N-(ortho-hydroxyphenyl)-N-methylcarbamate) and a phenolic nitrogen mustard was synthesised. As this prodrug was easily cleaved by a β-glucuronidase enzyme and displayed lo