ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSynthesis and chemistry of N-oxygenated pyrroles: crystal and molecular structure of a highly stable N-hydroxypyrrole 18-crown ether hydrateJohn F. W. Keana, Gwi Suk Heo, Jeffry S. Mann, Faith L. Van Nice, Laszlo Lex, Vaikunth S. Prabhu, and George FergusonCite this: J. Org. Chem. 1988, 53, 10, 2268–2274Publication Date (Print):May 1, 1988Publication History Published online1 May 2002Published inissue 1 May 1988https://pubs.acs.org/doi/10.1021/jo00245a026https://doi.org/10.1021/jo00245a026research-articleACS PublicationsRequest reuse permissionsArticle Views996Altmetric-Citations15LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-AlertscloseSupporting Info (1)»Supporting Information Supporting Information Get e-Alerts
Abstract Ausgehend vom Nitroester (I) ‐ zugänglich aus Dehydroisoandrosteron ‐ wird über die Stufen (II) und (III) das Cholesterin‐nitroxid (IV) synthetisiert [neben (IV) werden auch die neuen Steroide (V)‐(VII) erhalten; (VI) liefert weiter durch Cu‐acetatkatalysierte Luft‐Oxidation das Nitroxid (VIII)].
A series of aromatic and azepine ring-modified analogs of 3-hydroxy-1H-1-benzazepine-2,5-dione (HBAD) were synthesized and evaluated as antagonists at NMDA receptor glycine sites. Aromatic ring-modified HBADs were generally prepared via a Schmidt reaction with substituted 2-methoxynaphthalene-1,4-diones followed by demethylation. Electrophilic aromatic substitution of benzazepine 3-methyl ethers gave 7-substituted analogs. The preparation of multiply substituted 2-methoxynaphthalene-1,4-diones was effected via Diels−Alder methodology utilizing substituted butadienes with 2-methoxybenzoquinones followed by aromatization. Structural modifications, such as elimination of the aromatic ring, removal of the 3-hydroxyl group, and transfer of the hydroxyl group from C-3 to C-4, were also studied. An initial evaluation of NMDA antagonism was performed using a [3H]MK801 binding assay. HBADs demonstrating NMDA antagonist activity as indicated by inhibition of [3H]MK801 binding were further evaluated employing a [3H]-5,7-dichlorokynurenic acid (DCKA) glycine site binding assay. Selected HBADs were characterized for functional antagonism of NMDA and AMPA receptors using electrophysiological assays in Xenopus oocytes and cultured rat cortical neurons. Antagonist potency of HBADs showed good correlation between the different assay systems. HBADs substituted at the 8-position possessed the highest potency with the 8-methyl (5), 8-chloro (6), and 8-bromo (7) analogs being the most active. For HBAD 6, the IC50 in [3H]DCKA binding assays was 0.013 μM and the Kb values for antagonism of NMDA receptors in oocytes (NR1a/2C) and cortical neurons were 0.026 and 0.048 μM, respectively. HBADs also antagonized AMPA-preferring non-NMDA receptors expressed in oocytes but at a lower potency than corresponding inhibition of NMDA receptors. HBADs demonstrating a high potency for NMDA glycine sites showed the highest steady-state selectivity index relative to AMPA receptors. Substitution at the 6-, 7-, and 9-positions generally reduced or eliminated glycine site affinity. Moving the hydroxyl group from C-3 to C-4 reduced receptor affinity, and potency was eliminated by the removal of the aromatic ring or the hydroxyl group. These data indicate that the HBAD series has specific structural requirements for high receptor affinity. With the exception of substitution at C-8, modified HBADs generally have a lower affinity at NMDA receptor glycine sites than the parent compound 3. Mouse maximum electroshock-induced seizure studies show that the three HBADs selected for testing have in vivo potency with the 6,8-dimethyl analog (52) being the most potent (ED50 = 3.9 mg/kg, iv).
Many important structural problems in biology can be approached if particular components in an assembly can be labeled with a reagent that is detectable in an electron microscope. The development of the high resolution STEM, able to image single heavy atoms, raised the possibility of using individual atoms as labels. However, the imaging of single atoms requires very high dosages which are damaging to the specimen. To avoid this the undecagold cluster compound was introduced by Bartlett et al. (1978).
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTDiels-Alder reactions involving heterocyclic dienophiles. Synthesis of substituted hydroquinazolines and 1,3-diazaspiro[4.5]decadienesJohn F. W. Keana, Jeffrey S. Bland, Paul E. Eckler, Victor Nelson, and J. Z. GougoutasCite this: J. Org. Chem. 1976, 41, 12, 2124–2129Publication Date (Print):June 1, 1976Publication History Published online1 May 2002Published inissue 1 June 1976https://pubs.acs.org/doi/10.1021/jo00874a012https://doi.org/10.1021/jo00874a012research-articleACS PublicationsRequest reuse permissionsArticle Views346Altmetric-Citations12LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-AlertscloseSupporting Info (1)»Supporting Information Supporting Information Get e-Alerts
