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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
3.
Younan N.H. Cox B.I. Taylor C.D. Prather W.D. 《Electromagnetic Compatibility, IEEE Transactions on》1994,36(4):394-398
Efficient numerical solution techniques have been developed and used to examine the electromagnetic fields that can be developed in the working volume of the CW Ellipticus antenna operated at frequencies from 100 kHz to 1 GHz. An exponentially tapered transition section is designed to obtain the desired illumination pattern in the working volume. The input transition section is needed for impedance matching and to drive efficiently the Ellipticus antenna. A parametric study is performed to ascertain the performance of the Ellipticus antenna for frequencies up to 1 GHz 相似文献
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Butyl, hexyl, and 2-ethylhexyl diesters of 1,1-bis(5-carboxyl-2-furyl)-2,2-dichloroethene, hexyl and 2-ethylhexyl diesters of 1,1-bis(5-carboxyl-2-furyl) ketone, and the hexyl diester of 1,1-bis(5-carboxyl-2-furyl)methane were synthesized from furfural and evaluated for their plasticizing abilities toward PVC, by the application of dynamic mechanical thermal analysis and [di(2-ethylhexyl) phthalate] as a standard of reference. © 1995 John Wiley & Sons, Inc. 相似文献
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We report on the Langmuir-Blodgett film deposition and plasma etching of cadmium distearate on n-Gao.47Ino.53As to form a high-barrier-height Schottky barrier. Using this technique to form the gate electrode, we fabricated a 1?m-gate-length inverted InP-GalnAs modulation-doped field-effect transistor (MODFET) with an extrinsic transconductance of 170mS/mm and a cutoff frequencyfT of 19 GHz. 相似文献
8.
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
9.
R.A. Cunningham N.E. Sanderson W.N.J. Snodgrass D.W. Banes S.D. Hoath J.N. Mo 《Nuclear instruments & methods in physics research. Section A, Accelerators, spectrometers, detectors and associated equipment》1985,234(1):67-80
The design, construction and performance of a modular, two pressure focal plane detector, 550 mm long, 1000 mm deep and with an active height of 60 mm are described. The detector has been operated with ions ranging from 50 MeV 1H to 200 MeV 36S. Typical results achieved are 0.5 mm and 0.3° for the spatial and angular resolutions, and 0.7% and 3% for the total energy and energy loss measurements. A height signal is also provided. 相似文献
10.
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