- Identification, synthesis, and characterization of a unique class of N- methyl-D-aspartate antagonists. The 6,11-ethanobenzo[b]quinolizinium cation
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A series of novel N-methyl-D-aspartate antagonists acting at the phencyclidine site has been identified. Compound 2 has a K(i) = 8 ± 1 nM (vs [3H]thienylcyclidine, [3H]TCP) as a mixture of enantiomers. Resolution and further testing indicate that (-)-2, K(i) = 4 ± 0.7 nM, is a potent and selective TCP site ligand with neuroprotective activity in cultured neurons in the presence of excitotoxic concentrations of NMDA (IC50 = 26 nM). Compound (-)-2 is > 1000-fold selective for the TCP site vs a panel of receptor types including opiate, adrenergic, serotonergic, dopamine, adenosine, dihydropyridine, and benzodiazepine and displays increased selectivity for the activated (open) NMDA receptor-ion channel complex vs PCP and MK801 as measured by patch recordings in cultured, voltage-clamped neurons. Highly enhanced 'open-channel' selectivity leads to tentative classification of these ligands as uncompetitive vs NMDA. Ligands with these characteristics may enable deconvolution of the pharmacologic effects associated with typical noncompetitive NMDA antagonists. We report here on the identification, synthesis, and activity of compounds of this structural class.
- Mallamo,Earley,Kumar,Subramanyam,Dority Jr.,Miller,Dehaven-Hudkins,Ault,Herrmann Jr.,Dung,McMullen,Jaeger,Kullnig,Magee
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- Trichloroisocyanuric Acid Oxidation of 2-Chloro Aldehyde Acetals to 2-Chloro Acids Esters
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2-Chloro acid methyl esters were prepared in good yields treating 2-chloro aldehyde dimethyl acetals with trichloroisocyanuric acid in DMF.Aldehyde dimethyl acetals with the 2-halogen on a tertiary carbon atom were poorly reactive and could be oxidized efficiently only after their transformation into 1,3-dioxolanes.
- Boni, Monica,Ghelfi, Franco,Pagnoni, Ugo Maria,Pinetti, Adriano
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p. 156 - 159
(2007/10/02)
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