130,559 research outputs found
Piperazine-and piperidine-containing thiazolo[5,4-d]pyrimidine derivatives as new potent and selective adenosine a2a receptor inverse agonists
No full textThe therapeutic use of A2A adenosine receptor (AR) antagonists for the treatment of neurodegenerative disorders, such as Parkinson and Alzheimer diseases, is a very promising approach. Moreover, the potential therapeutic role of A2A AR antagonists to avoid both immunoescaping of tumor cells and tumor development is well documented. Herein, we report on the synthesis and biological evaluation of a new set of piperazine-and piperidine-containing 7-amino-2-(furan-2-yl)thiazolo[5,4-d]pyrimidine derivatives designed as human A2A AR antagonists/inverse agonists. Binding and potency data indicated that a good number of potent and selective hA2A AR inverse agonists were found. Amongst them, the 2-(furan-2-yl)-N5-(2-(4-phenylpiperazin-1-yl)ethyl)thiazolo[5,4-d]pyrimidine-5,7-diamine 11 exhibited the highest A2A AR binding affinity (Ki = 8.62 nM) as well as inverse agonist potency (IC50 = 7.42 nM). In addition, bioinformatics prediction using the web tool SwissADME revealed that 8, 11, and 19 possessed good drug-likeness profiles
Tricyclic heteroaromatic systems. Synthesis and benzodiazepine receptor affinity of 2-substituted-1-benzopyrano[3,4-d]oxazol-4-ones, -thiazol-4-ones, and -imidazol-4-ones
No full textA number of 2-aryl-substituted-1-benzopyrano[3,4-d] oxazol-4-ones 1, -thiazol-4-ones 2 and -imidazol-4-ones 3 were synthesized. Benzodiazepine receptor (BZR) binding assays were performed on these series of tricyclic heteroaromatic systems. None of the tested compounds showed detectable affinity for BZR. Comparative structure-activity relationship analysis between the reported compounds and some known BZR ligands of similar size and shape revealed that, according to a two-dimensional schematic representation of the interaction of these kinds of tricyclic heteroaromatic systems with the BZR recognition site, the nature of the optional a. proton acceptor is of significant importance in the receptor-ligand interaction. (C) 1998 Elsevier Science S.A. All rights reserved
New Tunneled Buccal Fat Pad Flap for Palatal Reconstruction
No full textIn the palatal defects due to surgical resection, flap selection is very important for a correct reconstruction. Different methods have been suggested over the time, however the pedicled buccal fat pad is a simple, effective, reliable flap for reconstruction after palate tumor resection. The aim of the present study is to introduce a new surgical technique for palate reconstruction with pedicled buccal fat pad flap exposing the advantages. The Authors performed this procedure in 17 patients in order to treat medium-sized oncologic surgical defect of palate region in the period between 2016 and 2019. Complete wound healing after only 4 weeks without complication after 12 months follow-up was observed. This is the first cases series described with this new technique
Design and synthesis of novel thiazolo[5,4-d]pyrimidine derivatives with high affinity for both the adenosine a1 and a2a receptors, and efficacy in animal models of depression
No full textNew compounds with a 7-amino-2-arylmethyl-thiazolo[5,4-d]pyrimidine structure were synthesized and evaluated in vitro for their affinity and/or potency at the human (h) A1, hA2A, hA2B, and hA3 adenosine receptors (ARs). Several compounds (5, 8–10, 13, 18–19) were characterized by nanomolar and subnanomolar binding affinities for the hA1 and the hA2A AR, respectively. Results of molecular docking studies supported the in vitro results. The 2-(2-fluorobenzyl)-5-(furan-2yl)-thiazolo[5,4-d]pyrimidin-7-amine derivative 18 (hA1 Ki = 1.9 nM; hA2A Ki = 0.06 nM) was evaluated for its antidepressant-like activity in in vivo studies, the forced swimming test (FST), the tail suspension test (TST), and the sucrose preference test (SPT) in mice, showing an effect comparable to that of the reference amitriptyline
Identification of novel thiazolo[5,4-d]pyrimidine derivatives as human A1 and A2A adenosine receptor antagonists/inverse agonists
No full textIn this study a new set of thiazolo[5,4-d]pyrimidine derivatives was synthesized. These derivatives bear different substituents at positions 2 and 5 of the thiazolopyrimidine core while maintaining a free amino group at position-7. The new compounds were tested for their affinity and potency at human (h) A1, A2A, A2Band A3adenosine receptors expressed in CHO cells. The results reveal that the higher affinity of these new set of thiazolopyrimidines is toward the hA1and hA2Aadenosine receptors subtypes and is tuned by the substitution pattern at both the 2 and 5 positions of the thiazolopyrimidine nucleus. Functional studies evidenced that the compounds behaved as dual A1/A2Aantagonists/inverse agonists. Compound 3, bearing a 5-((2-methoxyphenyl) methylamino) group and a phenyl moiety at position 2, displayed the highest affinity (hA1Ki= 10.2 nM; hA2AKi= 4.72 nM) and behaved as a potent A1/A2Aantagonist/inverse agonist (hA1IC50= 13.4 nM; hA2AIC50= 5.34 nM)
MeSH term explosion and author rank improve expert recommendations
No full textInformation overload is an often-cited phenomenon that reduces the productivity, efficiency and efficacy of scientists. One challenge for scientists is to find appropriate collaborators in their research. The literature describes various solutions to the problem of expertise location, but most current approaches do not appear to be very suitable for expert recommendations in biomedical research. In this study, we present the development and initial evaluation of a vector space model-based algorithm to calculate researcher similarity using four inputs: 1) MeSH terms of publications; 2) MeSH terms and author rank; 3) exploded MeSH terms; and 4) exploded MeSH terms and author rank. We developed and evaluated the algorithm using a data set of 17,525 authors and their 22,542 papers. On average, our algorithms correctly predicted 2.5 of the top 5/10 coauthors of individual scientists. Exploded MeSH and author rank outperformed all other algorithms in accuracy, followed closely by MeSH and author rank. Our results show that the accuracy of MeSH term-based matching can be enhanced with other metadata such as author rank
2-Phenylpyrazolo[4,3-d]pyrimidin-7-one as a New Scaffold To Obtain Potent and Selective Human A(3) Adenosine Receptor Antagonists: New Insights into the Receptor-Antagonist Recognition
No full textA molecular simplification approach of previously reported 2-arylpyrazolo[3,4-c]quinolin-4-ones was applied to design 2-arylpyrazolo[4,3-d]pyrimidin-7-one derivatives as new human A(3) adenosine receptor antagonists. Substituents with different lipophilicity and steric hindrance were introduced at the 5-position of the bicyclic scaffold (R(5) = H, Me, Et, Ph, CH(2)Ph) and on the 2-phenyl ring (OMe, Me). Most of the synthesized derivatives were highly potent hA(3) adenosine receptor antagonists, the best being the 2-(4-methoxyphenyl)pyrazolo[4,3-d]pyrimidin-7-one (K(i) = 1.2 nM). The new compounds were also highly selective, being completely devoid of affinity toward hA(1), hA(2A), and hA(2B) adenosine receptors. On the basis of the recently published human A(2A) receptor crystallographic information, we propose a novel receptor-driven hypothesis to explain both A(3) AR affinity and A(3) versus A(2A) selectivity profiles of these new antagonists
2-Phenylpyrazolo[4,3-d]pyrimidin-7-one as a New Scaffold To Obtain Potent and Selective Human A(3) Adenosine Receptor Antagonists: New Insights into the Receptor-Antagonist Recognition (dagger).
No full textA molecular simplification approach of previously reported 2-arylpyrazolo[3,4-c]quinolin-4-ones was applied to design 2-arylpyrazolo[4,3-d]pyrimidin-7-one derivatives as new human A3 adenosine receptor antagonists. Substituents with different lipophilicity and steric hindrance were introduced at the 5-position of the bicyclic scaffold (R5 = H, Me, Et, Ph, CH2Ph) and on the 2-phenyl ring (OMe, Me). Most of the synthesized derivatives were highly potent hA3 adenosine receptor antagonists, the best being the 2-(4-methoxyphenyl)pyrazolo[4,3-d]pyrimidin-7-one (Ki = 1.2 nM). The new compounds were also highly selective, being completely devoid of affinity toward hA1, hA2A, and hA2B adenosine receptors. On the basis of the recently published human A2A receptor crystallographic information, we propose a novel receptor-driven hypothesis to explain both A3 AR affinity and A3 versus A2A selectivity profiles of these new antagonists
Going Beyond Counting First Authors in Author Co-citation Analysis
No full textThe 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
"Closing the R&D Gap, Evaluating the Sources of R&D Spending"
No full textBoth spending and tax policies have been implemented in the United States with the goal of stimulating private sector research and development (R&D). Karier questions whether current R&D policy, especially the research and experimentation tax credit, can contribute to closing the gap between nondefense expenditures on R&D in the United States and such expenditures in other countries, such as Japan and Germany. He also explores possible changes to our current R&D policy to make it more effective.
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