1,720,961 research outputs found
Synthesis and pharmacological evaluation of 4,4a,5,6-tetrahydro-7,8-disubstituted-benzo[h]cinnolin-3(2H)-ones
No full textSynthesis and pharmacological evaluation of 5,6-dihydrobenzo[f] cinnolin-2(3H)ones analogues of antihypertensive and antiaggregating benzo[h]cinnolinones
No full textC-alkylpiperazines. XII. Synthesis and diuretic activity of compounds structurally related to clopamide
No full textThe synthesis and diuretic activity were reported of a series of N1-(4-chloro-3-sulfamoylbenzamide)-N4-alkylpiperazines, 2-methyl- and cis-2,6-dimethyl substituted, structurally related to clopamide, as well as of two N4-alkyl-N1-(4-chloro-3-sulfamoylbenzoyl)-2-methyl-1,2,3, 4-tetrahydroquinoxalines. In the piperazine series the presence of methyl group in position 2 and 6 of the piperazinic ring was found to increase the diuretic potency of the C-unmethylated compound
6-Halogen derivatives of 2-(3-benzoylphenyl)propionic acid.
No full textThe synthesis of the 6-fluoro (I a), 6-chloro (I b) and 6-bromo (I c) derivatives of the known antiinflammatory agent 2-(3-benzoylphenyl)propionic acid (ketoprofen) is reported. The procedure employed involves the direct phase-transfer methylation of the appropriate arylacetonitriles and the subsequent hydrolysis of the alpha-methyl arylacetonitriles (V) thus obtained. It is noteworthy that (V b) and (V c) were not accompanied by alpha, alpha-dimethylated contaminants, owing to the steric hindrance of the chloro and bromine substituent. The pharmacological evaluation of (I a-c) showed that the presence of the halogen unexpectedly abolished the antiinflammatory and antipyretic activities of the model drug. The 6-ethoxy derivative (I d), isolated as by-product of the synthesis of (I a) was also found inactive. A hypothesis has been formulated on the loss of activity of these compounds
SYNTHESIS AND PHARMACOLOGICAL EVALUATION OF A NEW SERIES OF SUBSTITUTED BENZOYL-GAMMA-BUTYROLACTONE DERIVATIVES
No full textA series of substituted benzoyl-gamma-butyrolactones (1-3) has been synthesized and tested for their ability to affect central dopaminergic and GABAergic function in comparison to gamma-butyrolactone (GEL). Similarly to GEL, alpha-, beta- and gamma-substituted GBLs 1-3 with one or more chlorine on the phenyl ring were found to induce central depressant effects in rats, though at different degrees. However, the test compounds modified dopamine (DA) metabolism in rat striatum differently from GEL. In fact, whereas GEL increased both DA and dihydroxyphenylacetic acid (DOPAC) content, GEL derivatives 1-3 increased DA levels, but reduced the DOPAC concentration. Moreover, some of them, unlike GEL, effectively antagonized pentylenetetrazole (PTZ)-induced seizures in mice. In particular, alpha-3,5-dichlorobenzoyl-GBL (1g) was effective at a dose as low as 36 mg/kg in decreasing the number of animals having convulsions. However, in vitro addition and in vivo administration of the test compounds failed to modify [S-35]-t-butylbicyclo-phosphorothionate ([S-35]-TBPS) binding, which is a very sensitive tool for revealing changes in the GABAergic function
Synthesis and pharmacological evaluation of thienocinnoli-3-(2H)-ones, bioisosters of antihypertensive and antithrombotic benzo(h)cinnolinones
No full text
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
Multitarget-directed tricyclic pyridazinones as g protein-coupled receptor ligands and cholinesterase inhibitors.
No full textBy following a multitarget ligand design approach, a library of 47 compounds was prepared, and they were tested as binders of selected G protein-coupled receptors (GPCRs) and inhibitors of acetyl and/or butyryl cholinesterase. The newly designed ligands feature pyridazinone-based tricyclic scaffolds connected through alkyl chains of variable length to proper amine moieties (e.g., substituted piperazines or piperidines) for GPCR and cholinesterase (ChE) molecular recognition. The compounds were tested at three different GPCRs, namely serotoninergic 5-HT1A, adrenergic a1A, and dopaminergic D2 receptors. Our main goal was the discovery of compounds that exhibit, in addition to ChE inhibition, antagonist activity at 5-HT1A because of its involvement in neuronal deficits typical of Alzheimer’s and other neurodegenerative diseases. Ligands with nanomolar
affinity for the tested GPCRs were discovered, but most of them behaved as dual antagonists of a1A and 5-HT1A receptors. Nevertheless, several compounds displaying this GPCR affinity profile also showed moderate to good inhibition of AChE and BChE, thus deserving further investigations to exploit the therapeutic potential of such unusual biological profiles
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
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