125010-32-4Relevant academic research and scientific papers
Model Experiments pertaining to the Mechanism of Action of Vitamin B12-dependent α-Methyleneglutarate Mutase
Ashwell, Susan,Davies, Alwyn G.,Golding, Bernard T.,Hay-Motherwell, Robyn,Mwesigye-Kibende, Samson
, p. 1483 - 1485 (1989)
Photolysis of di-t-butyl 1-bromomethylcyclopropane-1,2-dicarboxylate (1a) in cyclopropane containing triethylsilane and di-t-butyl peroxide gave the 4-methylenepent-2-yl-1,5-dioic acid radical (3c), which was also produced from treatment of (1a), its cis-isomer (2b), di-t-butyl-2-bromo-4-methyleneglutarate (3a), or di-t-butyl 2-bromomethyl-3-methylenesuccinate (4b), with triphenyltin hydride; these experiments support a mechanism via proteinbound free radicals for the B12-dependent enzyme α-methyleneglutarate mutase.
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
Feng, Yan,Coward, James K.
, p. 770 - 788 (2007/10/03)
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.
NAALADase inhibitors useful as pharmaceutical compounds and compositions
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, (2008/06/13)
The present invention relates to N-Acetylated α-Linked Acidic Dipeptidase (NAALADase) inhibitors enzyme activity, pharmaceutical compositions comprising such inhibitors, and methods of their use to inhibit NAALADase enzyme activity, thereby effecting neur
Design and pharmacological activity of phosphinic acid based NAALADase inhibitors
Jackson,Tays,Maclin,Ko,Li,Vitharana,Tsukamoto,Stoermer,Lu,Wozniak,Slusher
, p. 4170 - 4175 (2007/10/03)
A novel series of phosphinic acid based inhibitors of the neuropeptidase NAALADase are described in this work. This series of compounds is the most potent series of inhibitors of the enzyme described to date. In addition, we have shown that these compounds are protective in animal models of neurodegeneration. Compound 34 significantly prevented neurodegeneration in a middle cerebral artery occlusion model of cerebral ischemia. In addition, in the chronic constrictive model of neuropathic pain, compound 34 significantly attenuated the hypersensitivity observed with saline-treated animals. These data suggest that NAALADase inhibition may provide a new approach for the treatment of both neurodegenerative disorders and peripheral neuropathies.
Methods for treating anxiety, anxiety disorders and memory impairment using naaladase inhibitors
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, (2008/06/13)
The present invention relates to methods of using NAALADase inhibitors for treating glutamate-mediated diseases, disorders and conditions selected from the group consisting of anxiety, anxiety disorders and memory impairment.
Phosphinic alkanoic acid derivatives
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, (2008/06/13)
The present invention relate to phosphinic alkanoic acid derivatives that inhibit N-Acetylated alpha -Linked Acidic Dipeptidase (NAALADase) enzyme activity, pharmaceutical compositions comprising the same, and methods of using the same to inhibit NAALADas
