1,721,015 research outputs found
Determinazione di un modello 3D QSAR per una serie di antagonisti xantinici al recettore adenosinico umano A2B
No full textNew synthesis of diazepino[3,2,1-ij]quinoline and pyrido[1,2,3-de] quinoxalines via addition-elimination followed by cycloacylation
No full textThis paper describes a convenient and efficient synthesis of new fused tricyclic diazepino[3,2,1-ij]quinolines and substituted pyrido[1,2,3-de] quinoxalines. o-Phenylenediamines are transformed in the tricycle nucleus in only a few-step synthetic sequence to produce ethyl 2,8-dioxo-1,2,3,4- tetrahydro-8H [1,4]diazepino[3,2,1-ij]quinoline-7-carboxylate, ethyl 8-oxo-1,2,3,4-tetrahydro-8H-[1,4]diazepino[3,2,1-ij]quinoline-7-carboxylate and ethyl 2,7-dioxo-2,3-dihydro-1H,7H-pyrido[1,2,3-de]quinoxaline-6-carboxylate. The method is economical and simple to perform. © 2013 HeteroCorporation
Binding of the radioligand [3H]-SCH 58261, a new non-xanthine A2A adenosine receptor antagonist, to rat striatal membranes
No full textThe present study describes the binding to rat striatal A2A adenosine receptors of the new potent and selective antagonist radioligand, [3H]-5-amino-7-(2-phenylethyl)-2-(2-furyl)-pyrazolo[4,3-e]-1,2,4-triazolo[1,5-c]pyrimidine, [3H]-SCH 58261. [3H]-SCH 58261 specific binding to rat striatal membranes (>90%) was saturable, reversible and dependent upon protein concn. Satn. expts. revealed that [3H]-SCH 58261 labeled a single class of recognition sites with high affinity (Kd = 0.70 nM) and limited capacity (apparent Bmax = 971 fmol mg-1 of protein). The presence of 100 μM GTP in the incubation mixt. did not modify [3H]-SCH 58261 binding parameters. Competition expts. showed that [3H]-SCH 58261 binding is consistent with the labeling of A2A striatal receptors. Adenosine receptor agonists competed with the binding of 0.2 nM [3H]-SCH 58261 with the following order of potency: 2-hexynyl-5'-ethylcarboxamidoadenosine (2HE-NECA)>5'-N-ethylcarboxamidoadenosine (NECA)>2-[4-(2-carboxyethyl)phenethylamino]-5'-N-ethylcarboxamidoadenosine (CGS 21680)>2-phenylaminoadenosine (CV 1808)>R-N6-phenylisopropyladenosine (R-PIA)>N6-cyclohexyladenosine (CCPA)>S-N6-phenylisopropyladenosine (S-PIA). Adenosine antagonists inhibited [3H]-SCH 58261 binding in the following order: 5-amino-9-chloro-2-(furyl)-[1,2,4]-triazolo[1,5-c]quinazoline (CGS 15943)>5-amino-8-(4-fluorobenzyl)-2-(2-furyl)pyrazolo[4,3-e]-1,2,4-triazolo[1,5-c]pyrimidine (8FB-PTP)=SCH 58261>xanthine amine congener (XAC)=(E,18%-Z,82%)7-methyl-8-(3,4-dimethoxystyryl)-1,3-dipropylxanthine (KF 17837S)>8-cyclopentyl-1,3-dipropylxanthine (DPCPX)≥8-phenyltheophylline (8-PT). The Ki values for adenosine antagonists were similar to those labeled with the A2A agonist [3H]-CGS 21680. Affinities of agonists were generally lower. The A1-selective agonist, R-PIA, was found to be about 9 fold more potent than its stereoisomer, S-PIA, thus showing the stereoselectivity of [3H]-SCH 58261 binding. Except for 8-PT, the adenosine agonists and antagonists examd. inhibited [3H]-SCH 58261 binding with Hill coeffs. not significantly different from unity. The present results indicate that [3H]-SCH 58261 is the first non-xanthine adenosine antagonist radioligand which directly labels A2A striatal receptors. High receptor affinity, good selectivity and very low non-specific binding make [3H]-SCH 58261 an excellent probe for studying the A2A adenosine receptor subtype in mammalian brain
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Elaboration of the ωChain of 11 -Deoxyprostanoid Derivatives through Isoxazole Intermediates
No full textA new versatile approach to the synthesis of ll-deoxyprostanoic acid derivatives, which entails the use of
3,&diaubatituted iaoxazoles as source of the eight carbon atoms of the wchain, is degcribed. The key step involves
the formation of the C(13)<(14) bond through a [3 + 21 cycloaddition of the nitrile oxides generated from
3~-(nitromethyl)-2a-substituted-cyclopentanoncey cloethylene ketals (10,22,31) to l-heptyne to give the corresponding
isoxazoles (12,24,32), the wide chain of 24 and 32 being completed through Wittig condensation
to give 26 and 36. Reductive ring opening of the heterocycle under Birch-like conditions gave rise to the &amino
ketones 14,27, and 37, which underwent a silica gel assisted loss of ammonia to produce the a,b-unsaturated
ketones 15,28, and 38, precursors of the vinylamylcarbinol side chain of prostaglandins (PGs). The alternative
reductive ring opening of the isoxazole 12 allowed us to obtain the allylically transposed enone 19, leading to
a new preparation of 13-hydroxyprostanoic acid derivatives 21
Enzymatic synthesis of 2’-O-acyl-prodrugs of 1-(beta-D-arabinofuranosyl)-5(E)-(2-bromovinyl)uracil (sorivudine, BV-araU) and of 2’-O-acyl-araU, -araC and -araA.
No full textPig liver esterase (EC 3.1.1.1) catalysed regioselective hydrolysis of 1-(2,3,5-tri-O-acyl-beta-D-arabinofuranosyl)uracil, -cytosine and -adenine to give the corresponding 2'-monoesters effectively and in high yield. This methodology enabled the preparation of 1-(2-O-acyl-beta-D-arabinofuranosyl)-5-[(E)-(2-bromovinyl)]uracil prodrugs which, although slightly less active than the parent 1-(beta-D-arabinofuranosyl)-5-(E)-(2 bromovinyl)uracil (sorivudine; BV-araU), were strongly active in vitro against varicella-zoster virus (ED50 2.4-45 ng/ml). The retarded rates of enzymatic hydrolysis of the 2'-esters imply that they might function as lipophilic prodrugs, leading to increased plasma and cellular concentrations. In view of the marked in vitro activity, they represent an interesting approach to arabinofuranosyl nucleoside prodrugs with improved pharmacokinetics and enzymatic stability
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