827614-64-2Relevant articles and documents
Transition metal complex, polymer, mixture, composition and organic electronic device
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Paragraph 0240-0243; 0371-0374, (2020/05/01)
The invention discloses a transition metal complex, a polymer, a mixture, a composition and an organic electronic device. The transition metal complex has a structural general formula represented by achemical formula (1), and is simple to synthesize, novel in structure, relatively good in stability, long in service life and good in light emitting performance; the compound represented by the chemical formula (1) is convenient for realizing an efficient, high-brightness and high-stability OLED device, and a relatively good material option is provided for full-color display and illumination application.
Design, Synthesis, and Pharmacological Evaluation of First-in-Class Multitarget N-Acylhydrazone Derivatives as Selective HDAC6/8 and PI3Kα Inhibitors
Alves, Marina A.,Chaves, Lorrane S.,Fernandes, Patrícia D.,Fraga, Carlos A. M.,Guerra, Fabiana S.,Rodrigues, Daniel A.,Sagrillo, Fernanda S.,Sant'Anna, Carlos M. R.,Thota, Sreekanth,de Sena M. Pinheiro, Pedro
, (2020/02/25)
Targeting histone deacetylases (HDACs) and phosphatidylinositol 3-kinases (PI3Ks) is a very promising approach for cancer treatment. This manuscript describes the design, synthesis, in vitro pharmacological profile, and molecular modeling of a novel class of N-acylhydrazone (NAH) derivatives that act as HDAC6/8 and PI3Kα dual inhibitors. The surprising selectivity for PI3Kα may be related to differences in the conformation in the active site. Cellular studies showed that these compounds act in HDAC6 inhibition and the PI3/K/AKT/mTOR pathway. The compounds that are selective for inhibition of HDAC6/8 and inhibit PI3Kα show potential for the treatment of cancer.
Development of novel 2,4-bispyridyl thiophene–based compounds as highly potent and selective Dyrk1A inhibitors. Part I: Benzamide and benzylamide derivatives
Darwish, Sarah S.,Abdel-Halim, Mohammad,Salah, Mohamed,Abadi, Ashraf H.,Becker, Walter,Engel, Matthias
, p. 1031 - 1050 (2018/09/12)
The protein kinase Dyrk1A modulates several processes relevant to the development or progression of Alzheimer's disease (AD), e. g. through phosphorylation of tau protein, amyloid precursor protein (APP) as well as proteins involved in the regulation of alternative splicing of tau pre-mRNA. Therefore, Dyrk1A has been proposed as a potential target for the treatment of AD. However, the co-inhibition of other closely related kinases of the same family of protein kinases (e.g. Dyrk1B and Dyrk2) or kinases from other families such as Clk1 limits the use of Dyrk1A inhibitors, as this may cause unpredictable side effects especially over long treatment periods. Herein, we describe the design and synthesis of a series of amide functionalized 2,4-bispyridyl thiophene compounds, of which the 4-fluorobenzyl amide derivative (31b) displayed the highest potency against Dyrk1A and remarkable selectivity over closely related kinases (IC50: Dyrk1A = 14.3 nM; Dyrk1B = 383 nM, Clk1 > 2 μM). This degree of selectivity over the frequently hit off-targets has rarely been achieved to date. Additionally, 31b inhibited Dyrk1A in intact cells with high efficacy (IC50 = 79 nM). Furthermore, 31b displayed a high metabolic stability in vitro with a half-life of 2 h. Altogether, the benzamide and benzylamide extension at the 2,4-bispyridyl thiophene core improved several key properties, giving access to compound suitable for future in vivo studies.