1,721,011 research outputs found
Nuovi principi attivi e relative formulazioni per la terapia del dolore ed il trattamento dei tumori
No full textThe discovery of novel drugs for chronic pain treatment, as well as for chemotherapy, characterized by significant efficacy and reduced side effects is one of the main goals of the medicinal chemistry.
In this work, novel pyrazole cannabinoid ligands and diazabicycloalkyl delta opioid derivatives have been synthetized and their pharmacological profiles have been investigated to evaluate their potential application in chronic/inflammatory or neuropathic pain therapies. According to the determined pharmacological profiles, lead compounds belong to the investigated series may represent useful candidates for the treatment of these pathologies.
In addition, a novel fluorinated thiol endopeptidase inhibitor has been investigated as alternative strategy to manage inflammatory pain. The compound showed interesting pharmacological profile in formalin test by evidencing higher activity and improved bioavailability compared to reference inhibitors.
Considering the sparingly solubility of cannabinoidergic and opioidergic compounds, part of the work has been devoted to the obtainment and the characterization of injectable aqueous formulations of these agents based on microemulsion systems.
Novel tubulysin derivatives as innovative agents for chemotherapy have been synthetized through an improved process. The novel tubulysins evidenced high cytotoxicity towards various cancer cell lines and significant activity in an animal model of resistant tumor to conventional chemotherapic agents
Sintesi e valutazione biologica di carbossammidi pirazoliche tricicliche contenenti cicloalchili quali nuovi ligandi cannabinergici
No full textCannabinoid receptor ligands are potential candidates for the therapy of chronic pain, neuroinflammatory diseases, cancer and obesity. In preceding studies the relevance and structure-activity relationships (SAR) of pyrazole derivatives have been consolidated and clarified, and in the process three series of tricyclic compounds as 1,4,5,6-tetrahydrobenzo[6,7]cyclohepta[1,2-c]pyrazoles, 4,5-dihydro-1H-benzo[g]indazoles and 1,4-dihydroindeno[1,2-c]pyrazoles emerged as potent cannabinoid receptor ligands. In the present study five new series of 1,4-dihydroindeno[1,2-c]pyrazole and 1H-benzo[g]indazole carboxamides containing a cyclopropyl, cyclopentyl or cycloexyl substituent were designed and synthesized to evaluate their affinities towards CB1 and CB2 receptors. Among these derivatives, compound 38Am, exibits a high affinity for CB2 receptor (Ki = 4.48nM) together with remarkable selectivity (KiCB1/KiCB1 = 2232). It is interesting to note, in a in vitro neuroinflammatory test, that compound 3Am shows antagonist activity. Unexpectedly, compound 38Aa possess a agonistic biological profile
Sintesi e attività cannabinergica di nuove molecole a struttura 1H-4-Diidropirazolo[3,4-a]pirrolizinica, 1H-4,5-Diidropirazolo[4,3-g] indolizinica e 1H-4,5,6-Tetraidropirazolo[3,4-c]pirrolo[1,2-c]azepinica
No full textThe endocannabinoid system consist of two cannabinoids receptors CB1 and CB2, the endogenous ligands such as anandamide (AEA) and 2-arachidonoylglycerol (2-AG) and enzymes responsible for endogenous ligand synthesis (phospholipase D) and degradation (fatty acid amide
hydrolase, FAAH). Extensive preclinical and clinical data support the notion that cannabinoid receptors offer promising approach for the treatment of several pathologies including energy metabolic disorders, chronic inflammation, pain, menthal disfunctions, abuse, cancer, bone loss
and liver pathophysiology.
Recently, a research group at University of Sassari described the discovery of a novel series of
tricyclic pyrazoles of general structure 1 as ligands for cannabinoid receptors. On the basis of preliminary SAR study three derivatives (1Aa, Ba, Ca Chart 1) were identified as leads. It was envisioned that bioisosteric modification of these structure might offer novel templates that could provide optimized interactions with receptors. Thus, three different scaffolds including tricyclic
1.4-dihydropyrazol-pyrrolizine-, 1,4,5-dihydropyrazolo[4,3-g]indolizine-, and 1,4,5,6-
tetrahydropyrazol[3,4-c]pyrrolo[1,2-c]azepine systems (2A-C) were designed
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
Dispelling the Myths Behind First-author Citation Counts
Full text linkWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
Oxadiazoles having antiproliferative activity
No full textOxadiazole derivatives of general formula 1 in which X, Y, R and R2 have the meanings defined in the disclosure. The compounds have antiproliferative activity against a number of human tumors cell lines and can therefore be used for the preparation of antitumor medicaments
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