| Revision as of 09:43, 12 January 2015 edit82.26.141.64 (talk) →Synthesis← Previous edit | Revision as of 09:47, 12 January 2015 edit undo82.26.141.64 (talk) →SynthesisNext edit → | ||
| Line 46: | Line 46: | ||
| the pain to become chronic. Specific NMDA antagonists would thus be expected to relieve chronic pain by interrupting that chain. Consequently, such compounds would offer a potentially nonaddictive alternative to the opiates currently used to treat chronic pain. | the pain to become chronic. Specific NMDA antagonists would thus be expected to relieve chronic pain by interrupting that chain. Consequently, such compounds would offer a potentially nonaddictive alternative to the opiates currently used to treat chronic pain. | ||
| ==Synthesis== | ==Synthesis== | ||
| Reductive amination of the acetaldehyde derivative # with ]-] (#) leads to the now-disubstituted ] #. Reaction of this amine with the commercially available cyclobutenedione derivative # leads to replacement of one of the ethoxy groups in # by the free amino group in # by what is probably an |
Reductive amination of the acetaldehyde derivative # with ]-] (#) leads to the now-disubstituted ] #. Reaction of this amine with the commercially available cyclobutenedione derivative # leads to replacement of one of the ethoxy groups in # by the free amino group in # by what is probably an ] sequence to afford the coupled product #. | ||
| ] | ] | ||
Revision as of 09:47, 12 January 2015
Pharmaceutical compound | |
| Clinical data | |
|---|---|
| ATC code |
|
| Identifiers | |
IUPAC name
| |
| CAS Number | |
| PubChem CID | |
| ChemSpider | |
| UNII | |
| KEGG | |
| CompTox Dashboard (EPA) | |
| ECHA InfoCard | 100.222.780  |
| Chemical and physical data | |
| Formula | C9H13N2O5P |
| Molar mass | 260.184 g/mol g·mol |
| 3D model (JSmol) | |
SMILES
| |
InChI
| |
| (what is this?) (verify) | |
Perzinfotel (EAA-090) is a drug which acts as a potent NMDA antagonist. It has neuroprotective effects and has been investigated for the treatment of stroke, but lacks analgesic effects. Nevertheless it shows a good safety profile compared to older drugs, and further research is ongoing. To increase the low oral bioavailability of Perzinfotel (3-5%), prodrug derivatives were synthesized and evaluated.
Background
Pain receptors become sensitized during inflammation or from a related stimuli, and consequently often release glutamate. That amino acid then acts on NMDA receptors on neurons, and in the process further sensitizes those to pain stimuli. This sequence then causes the pain to become chronic. Specific NMDA antagonists would thus be expected to relieve chronic pain by interrupting that chain. Consequently, such compounds would offer a potentially nonaddictive alternative to the opiates currently used to treat chronic pain.
Synthesis
Reductive amination of the acetaldehyde derivative # with Carboxybenzyl-trimethylenediamine (#) leads to the now-disubstituted 1,3-Diaminopropane #. Reaction of this amine with the commercially available cyclobutenedione derivative # leads to replacement of one of the ethoxy groups in # by the free amino group in # by what is probably an addition-elimination reaction sequence to afford the coupled product #.
Reduction of this intermediate by hydrogen transfer from 1,4-cyclohexadiene in the presence of platinum leads to loss of the carbobenzoxy group and formation of the transient primary amine #. The terminal primary amino group in that product then participates in a second addition–elimination sequence to form an eight-membered ring (#). Treatment of this intermediate with trimethylsilyl bromide then cleaves the ethyl ethers on phosphorus to give the free phosphonic acid and thus perzinfotel.
References
- Kinney WA, Abou-Gharbia M, Garrison DT, Schmid J, Kowal DM, Bramlett DR, Miller TL, Tasse RP, Zaleska MM, Moyer JA. Design and synthesis of non-1(7)-en-2-yl)-ethyl]phosphonic acid (EAA-090), a potent N-methyl-D-aspartate antagonist, via the use of 3-cyclobutene-1,2-dione as an achiral alpha-amino acid bioisostere. Journal of Medicinal Chemistry. 1998 Jan 15;41(2):236-46. PMID 9457246
- Sun L, Chiu D, Kowal D, Simon R, Smeyne M, Zukin RS, Olney J, Baudy R, Lin S. Characterization of two novel N-methyl-D-aspartate antagonists: EAA-090 (2-non-1(7)-en2-yl]ethylphosphonic acid) and EAB-318 (R-alpha-amino-5-chloro-1-(phosphonomethyl)-1H-benzimidazole-2-propanoic acid hydrochloride). Journal of Pharmacology and Experimental Therapeutics. 2004 Aug;310(2):563-70. PMID 15075380
- Brandt MR, Cummons TA, Potestio L, Sukoff SJ, Rosenzweig-Lipson S. Effects of the N-methyl-D-aspartate receptor antagonist perzinfotel non-1(7)-en-2-yl)-ethyl]phosphonic acid] on chemically induced thermal hypersensitivity. Journal of Pharmacology and Experimental Therapeutics. 2005 Jun;313(3):1379-86. PMID 15764736
- Attention: This template ({{cite doi}}) is deprecated. To cite the publication identified by doi:10.1021/jm8011799, please use {{cite journal}} (if it was published in a bona fide academic journal, otherwise {{cite report}} with
|doi=10.1021/jm8011799instead.
| Hallucinogens | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Psychedelics (5-HT2A agonists) |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Dissociatives (NMDAR antagonists) |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Deliriants (mAChR antagonists) |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Others |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
 | This drug article relating to the nervous system is a stub. You can help Misplaced Pages by expanding it. |