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1.
Dr. Maria L. Di Paolo Dr. Michael S. Christodoulou Dr. Alessandra M. Calogero Dr. Luca Pinzi Prof. Giulio Rastelli Prof. Daniele Passarella Prof. Graziella Cappelletti Prof. Lisa Dalla Via 《ChemMedChem》2019,14(18):1641-1652
A series of 2-phenyloxazoles bearing an amide group at position 4 were designed and synthesized for evaluation as potential inhibitors of human recombinant monoamine oxidases (hrMAOs). Results of kinetics experiments demonstrated that all compounds behave as competitive MAO inhibitors, with good selectivity toward the MAO-B isoform. The most potent and selective derivatives are characterized by inhibition constant (Ki) values in the sub-micromolar range and a good selectivity index (Ki MAO-A/Ki MAO-B>50). Some derivatives were also found to be able to inhibit MAO activity in nerve growth factor (NGF)-differentiated PC12 cells, taken as a model of neuronal cells. In particular, 2-(2-hydroxyphenyl)-N-phenyloxazole-4-carboxamide (compound 4 a ) may be a promising new scaffold, exerting the highest selectivity and inhibitory effect toward MAOs in NGF-differentiated PC12 cell lysates, without compromising cell viability. Molecular docking analysis allowed a rationalization of the experimentally observed binding affinity and selectivity. 相似文献
2.
Dr. Yahu A. Liu Dr. Qihui Jin Qiang Ding Dr. Xueshi Hao Tingting Mo Shanshan Yan Dr. Yefen Zou Dr. Zhihong Huang Xiaoyue Zhang Wenqi Gao Dr. Tom Y.-H. Wu Chun Li Dr. Badry Bursalaya Dr. Michael Di Donato Dr. You-Qing Zhang Lisa Deaton Dr. Weijun Shen Dr. Brandon Taylor Anwesh Kamireddy Dr. George Harb Dr. Jing Li Dr. Yong Jia Dr. Andrew M. Schumacher Dr. Bryan Laffitte Dr. Richard Glynne Dr. Shifeng Pan Dr. Peter McNamara Dr. Valentina Molteni Dr. Jon Loren 《ChemMedChem》2020,15(16):1562-1570
Loss of β-cell mass and function can lead to insufficient insulin levels and ultimately to hyperglycemia and diabetes mellitus. The mainstream treatment approach involves regulation of insulin levels; however, approaches intended to increase β-cell mass are less developed. Promoting β-cell proliferation with low-molecular-weight inhibitors of dual-specificity tyrosine-regulated kinase 1A (DYRK1A) offers the potential to treat diabetes with oral therapies by restoring β-cell mass, insulin content and glycemic control. GNF4877, a potent dual inhibitor of DYRK1A and glycogen synthase kinase 3β (GSK3β) was previously reported to induce primary human β-cell proliferation in vitro and in vivo. Herein, we describe the lead optimization that lead to the identification of GNF4877 from an aminopyrazine hit identified in a phenotypic high-throughput screening campaign measuring β-cell proliferation. 相似文献
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Nichols M.A. Siegel H.J. Dietz H.G. Quong R.W. Nation W.G. 《Parallel and Distributed Systems, IEEE Transactions on》1991,2(3):290-303
Efficient data layout is an important aspect of the compilation process. A model for the creation of perfect memory maps for large-scale parallel machines capable of user-controlled partitionable single-instruction-multiple data/single-program-multiple data (SIMD/SPMD) operation is developed. The term perfect implies that no memory fragmentation occurs and ensures that the memory map size is kept to a minimum. A major constraint on solving this problem is based on the single program nature of both the SIMD and SPMD modes of parallelism. It is assumed that all processors within the same submachine used identical addresses to access corresponding data items in each of their local memories. Necessary and sufficient conditions are derived for being able to create perfect memory maps, and results are applied to several partitionable interconnection networks 相似文献
5.
McIntyre Christa K.; Marriott Lisa K.; Gold Paul E. 《Canadian Metallurgical Quarterly》2003,117(2):320
The present experiment examined the relationship between release of acetylcholine (ACh) in the amygdala and performance on a hippocampus-dependent spatial working memory task. Using in vivo microdialysis, the authors measured ACh release in rats during testing on a spontaneous alternation task. Amygdala ACh release was positively correlated with performance on the hippocampus-dependent task. These findings suggest that activation of the amygdala promotes processing in other neural systems important for learning and memory. (PsycINFO Database Record (c) 2010 APA, all rights reserved) 相似文献
6.
We could not imagine a more appropriate inauguration of the Psychology of Aesthetics, Creativity, and the Arts (PACA) going to four issues per year than with a special issue honoring the life and work of the great aesthetician and psychologist, Rudolf Arnheim. PACA is off to a great start. With this move to four issues per year, we are restarting our numbering system, so this special issue is Volume 1, Issue 1. As you read the articles in this issue, we hope that you enjoy reflecting on how much Rudolf Arnheim has contributed to the field of psychology of aesthetics. (PsycINFO Database Record (c) 2010 APA, all rights reserved) 相似文献
7.
In a conceptual replication of A. Biglan et al (see record 1989-39898-001), 288 Ss rated their emotional and behavioral responses to aggressive, distressed, and neutral behaviors. The stimulus behaviors occurred in the context of casual relationships and were portrayed by male and female actors. Consistent with Biglan et al, it was found that aggressive behaviors evoked angry emotions and negative behavioral responses; distressed behaviors evoked both angry and concerned emotions and supportive behavioral responses. However, in contrast to the original results, evidence was also found of negative (primarily avoidant) behavioral responses to distressed behavior. (PsycINFO Database Record (c) 2010 APA, all rights reserved) 相似文献
8.
This study evaluates the impact assessment methodologies used by Uganda's Water Hyacinth Control Programme in Lake Victoria, a domestic project with transboundary implications. The Control Programme sought to reduce infestations of water hyacinth (Eichhornia crassipes), an aquatic weed native to South America, through the use of integrated chemical, mechanical and biological methods. The environmental impact assessment for the project was conducted by Aquatics Unlimited, with support from the United States Agency for International Development. Although the case study involves a domestic impact assessment, it raised transboundary concerns. One of the major outcomes of the assessment was recognition of the need for informed involvement of the other riparian countries, Kenya and Tanzania, in the assessment process to ensure a regional effort among all three East African Community Partner States to control water hyacinth and other invasive weeds in Lake Victoria. 相似文献
9.
Marsch Lisa A.; Stephens Mary Ann Chutuape; Mudric Timothy; Strain Eric C.; Bigelow George E.; Johnson Rolley E. 《Canadian Metallurgical Quarterly》2005,13(4):293
This study examined (1) predictors of treatment outcome for opioid-dependent participants in a single-site controlled trial comparing methadone, buprenorphine, and LAAM treatments and (2) the extent to which various subpopulations of patients may have more successful outcomes with each medication. The relationships between patient demographics, drug use history, and psychological status and outcome measures of treatment retention, opiate use, and cocaine use were assessed. We believe this study to be the first to demonstrate that predictors of treatment success appear to be largely similar in LAAM, buprenorphine, and methadone treatment for opioid dependence. We did not find any factors that would strongly guide selection of one medication over others. (PsycINFO Database Record (c) 2010 APA, all rights reserved) 相似文献
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