166272-81-7Relevant articles and documents
Synthesis and crystal structure of 5-chloro-3,4-dihydroxy-3-(2-hydroxyethyl) isobenzofuran-1(3H)-one
Fu, Ying,Wang, Kui,Wang, Peng,Zhao, Ze-Yu,Wang, Yun-Kai,Ye, Fei
, p. 329 - 333 (2018/09/29)
5-Chloro-3,4-dihydroxy-3-(2-hydroxyethyl)isobenzofuran-1(3H)-one (C10H9ClO5, Mr=244.63) has been synthesized using 2-chloro-5-trifluoromethylphenol as starting material through esterification, Friedel-Crafts acylation, hydrolysis, and cyclization reaction. The compound was characterized by infrared (IR), 1H nuclear magnetic resonance (NMR), 13C NMR, and elemental analysis. The single crystal structure of the title compounds has been further determined by X-ray diffraction. The crystal belongs to the triclinic system, space group P1 with a=7.8111(16) ?, b=7.8164(16) ?, c=8.5660(17) ?, α=82.50(3)°, β=71.28(3)°, γ=68.22(3)°, V=459.93(16) ?3, Z=2, Dc=1.766 g/cm3, μ=0.418 mm?1, F(000)=252, the final R1=0.0792, and wR2(I>2σ(I))=0.2209. The existence of π-π conjunction effect resulted in correlative bond length shorter than typical bond length in the crystal. The title compound is assembled into a three-dimensional supramolecular structure by two intermolecular hydrogen bonds and one intramolecular hydrogen bond.
Structure-Based Design and Biological Characterization of Selective Histone Deacetylase 8 (HDAC8) Inhibitors with Anti-Neuroblastoma Activity
Heimburg, Tino,Kolbinger, Fiona R.,Zeyen, Patrik,Ghazy, Ehab,Herp, Daniel,Schmidtkunz, Karin,Melesina, Jelena,Shaik, Tajith Baba,Erdmann, Frank,Schmidt, Matthias,Romier, Christophe,Robaa, Dina,Witt, Olaf,Oehme, Ina,Jung, Manfred,Sippl, Wolfgang
, p. 10188 - 10204 (2018/01/10)
Histone deacetylases (HDACs) are important modulators of epigenetic gene regulation and additionally control the activity of non-histone protein substrates. While for HDACs 1-3 and 6 many potent selective inhibitors have been obtained, for other subtypes much less is known on selective inhibitors and the consequences of their inhibition. The present report describes the development of substituted benzhydroxamic acids as potent and selective HDAC8 inhibitors. Docking studies using available crystal structures have been used for structure-based optimization of this series of compounds. Within this study, we have investigated the role of HDAC8 in the proliferation of cancer cells and optimized hits for potency and selectivity, both in vitro and in cell culture. The combination of structure-based design, synthesis, and in vitro screening to cellular testing resulted in potent and selective HDAC8 inhibitors that showed anti-neuroblastoma activity in cellular testing.
Synthesis, structure-activity relationships, and biological evaluation of a series of benzamides as potential multireceptor antipsychotics
Yang, Feipu,Jiang, Xiangrui,Li, Jianfeng,Wang, Yu,Liu, Yongjian,Bi, Minghao,Wu, Chunhui,Zhao, Qingjie,Chen, Weiming,Yin, Jingjing,Zhang, Jian,Xie, Yuanchao,Hu, Tianwen,Xu, Mingshuo,Guo, Shuang,Wang, Zhen,He, Yang,Shen, Jingshan
supporting information, p. 3141 - 3147 (2016/06/13)
In the present study, a series of benzamides, endowed with potent dopamine D2, serotonin 5-HT1A and 5-HT2A receptors properties, was synthesized and evaluated as potential antipsychotics. Among them, 3-(4-(4-(6-fluorobenzo[d]isoxazol-3-yl)-piperidin-1-yl)butoxy)-N-methylbenzamide (21) and its fluoro-substituted analogue (22) held the best pharmacological binding profiles. They not only presented potent activities for D2, 5-HT1A, and 5-HT2A receptors, but were also endowed with low activities for 5-HT2C, H1 receptors and hERG channels, suggesting a low propensity of inducing weight gain and QT prolongation. In animal models, compounds 21 and 22 reduced phencyclidine-induced hyperactivity with a high threshold for catalepsy induction. It thus provides potential candidates for further preclinical studies.
