875667-98-4

Upstream product

• 56-86-0 L-glutamic acid 
• 16874-06-9 di-tert-butyl L-glutamate 
• 66891-86-9 benzyl (4-(chlorocarbonyl)phenyl)(methyl)carbamate 
• 501-53-1 benzyl chloroformate 
• 10541-83-0 N-methyl-p-aminobenzoic acid 
• 2528-30-5 4-<<(benzyloxy)carbonyl>methylamino>benzoic acid 
• 875667-97-3 (4-azidocarbonyl-phenyl)-methyl-carbamic acid benzyl ester 

Downstream Products

• 875668-00-1 bis(pivaloyloxymethyl) N-[4-(N-benzyloxycarbonyl-N-methyl)aminobenzoyl]-L-glutamate 
• 119830-06-7 bis(pivaloyloxymethyl) N-[4-(N-methylamino)benzoyl]-L-glutamate 
• 2528-31-6 (S)-2-[4-(Benzyloxycarbonyl-methyl-amino)-benzoylamino]-pentanedioic acid 
• 113311-21-0 di-tert-butyl (4-(methylamino)benzoyl)-L-glutamate 

Relevant academic research and scientific papers

PRODRUGS ACTIVATED BY REACTIVE OXYGEN SPECIES FOR USE IN THE TREATMENT OF INFLAMMATORY DISEASES AND CANCER

Prodrugs activated predominantly or exclusively in inflammatory tissue, more particularly prodrugs of methotrexate and derivatives thereof, which are selectively activated by Reactive Oxygen Species (ROS) in inflammatory tissues associated with cancer and inflammatory diseases, as well as method for preparing said prodrugs.

Prodrug forms of N-[(4-deoxy-4-amino-10-methyl)pteroyl]glutamate-γ- [ψP(O)(OH)]-glutarate, a potent inhibitor of folylpoly-γ-glutamate synthetase: Synthesis and hydrolytic stability

Ester prodrugs of the phosphinate pseudopeptide N-[(4-deoxy-4-amino-10- methyl)pteroyl]glutamate-γ-[ψP-(O)(OH)]-glutarate (1a) were synthesized. H-phosphinic acids derived from N-Cbz vinyl glycine esters were converted to the desired pseudopeptides by Michael addition to α-methyleneglutarate esters. Pivaloyloxymethyl (POM) ester moieties were incorporated in both the N-terminal and C-terminal fragments prior to formation of either C-P bond, N-Alkylation of the corresponding amides derived from N-(N-methyl)aminobenzoic acid with 2,4-diamino-6-(bromomethyl)pteridine gave the target compounds. POM esters of methotrexate and the corresponding γ-glutamyl conjugate were also synthesized using the same strategy. All prodrugs were evaluated in Chinese hamster ovary cells. Although the pseudopeptide prodrugs were ineffective, prodrugs of methotrexate and the corresponding γ-glutamyl conjugate were equipotent with the parent compounds. Stability of the prodrugs was investigated in both phosphate buffer and cell line medium to provide a rationale for the observed biological data.