15166-57-1Relevant academic research and scientific papers
Consecutive multicomponent syntheses of N-substituted 3-arylallylidene indolones – Solid-state emitters and photoisomerization
Müller, Thomas J. J.,Wilbert, Fabio
, (2021/11/30)
A series of variably substituted 3-arylallylidene indolones were synthesized as diastereomeric mixtures applying a novel consecutive three-component Heck-condensation sequence in the sense of a one-pot synthesis. The N-substitution pattern was found to be crucial for the fluorescence in the solid state. Accordingly, the synthetic route was extended to a consecutive four-component reaction to generate a diverse compound library of Boc-substituted 3-arylallylidene indolones. Studying the structure-property relationship by Hammett correlation revealed a discontinuous behavior of the longest wavelength absorption bands of these compounds. 3-Arylallylidene indolones exclusively fluoresce in the solid state. Exceptions are strongly donor-substituted derivatives, which also luminesce in solution and reveal positive emission solvatochromism. With the N-tosyl derivative, an AIE (aggregation induced emission) chromophore was discovered and for the (p-anisyl)2N-substituted derivative aggregation induced emission enhancement (AIEE) was found. The absorption spectra of the 3-arylallylidene indolones can be plausibly rationalized by TD(DFT) calculations. Interestingly, the diastereomers, which can be photoisomerized, are very similar in their photophysical properties.
Pharmacophore modeling and 3D-QSAR study for the design of novel α-synuclein aggregation inhibitors
Yang, Jixia,Hu, Jiajing,Zhang, Gongzheng,Qin, Li,Wen, Hongliang,Tang, Yun
, (2021/08/27)
Alpha-synuclein (α-syn), as a highly soluble presynaptic protein expressed in the brain, plays an important role in recycling synaptic vesicles and regulating the synthesis, storage, and release of neurotransmitters. Accumulation of α-syn in Lewy bodies and Lewy neurites is the pathological hallmark of Parkinson’s disease (PD), so inhibition of α-syn aggregation may provide a novel approach for treating PD. In this study, the 3D structure of α-syn was downloaded from Protein Data Bank (PDB ID: 2N0A). A ligand-based pharmacophore model was conducted on a set of 43 diverse α-syn ligands, and the results suggested that two hydrogen-bond acceptors, one hydrophobic group, and two aromatic rings were significant to the inhibition of α-syn aggregation. A ligand-based 3D-QSAR model was also established with good statistical significance (R2 = 0.920) and excellent predictive ability (Q2 = 0.752). Novel indolinone derivatives were designed and synthesized based on the pharmacophore model. Subsequently, the 3D-QSAR model was used to predict the inhibitory activities towards α-syn aggregation, and the actual inhibitory activities were evaluated by thioflavin-T assay in vitro with the best inhibitory activity reaching 45.08%. The fitting results indicated that the built pharmacophore and 3D-QSAR models provided better reliability and accuracy for compound modification and prediction of the activity thereof. Graphical abstract: A ligand-based pharmacophore modeling and 3D-QSAR study have been performed on a set of 43 diverse ligands for α-synuclein for the first time. Based on the best pharmacophore modeling, novel indolinone derivatives were designed and synthesized, and the inhibitory activities for α-synuclein aggregation were evaluated by thioflavin-T assay in vitro, which preliminary indicated that five pharmacophore sites (two hydrogen bond acceptors (A), a hydrophobic group (H), and two aromatic rings (R)) in compounds contribute to the inhibitory activities. In the study, the built pharmacophore modeling and 3D-QSAR provided better reliability and accuracy for compound modification and prediction of the activity thereof. [Figure not available: see fulltext.]
Design, Synthesis, and Characterization of 3-(Benzylidene)indolin-2-one Derivatives as Ligands for α-Synuclein Fibrils
Chu, Wenhua,Zhou, Dong,Gaba, Vrinda,Liu, Jialu,Li, Shihong,Peng, Xin,Xu, Jinbin,Dhavale, Dhruva,Bagchi, Devika P.,D'Avignon, André,Shakerdge, Naomi B.,Bacskai, Brian J.,Tu, Zhude,Kotzbauer, Paul T.,Mach, Robert H.
, p. 6002 - 6017 (2015/08/24)
A series of 3-(benzylidine)indolin-2-one derivatives were synthesized and evaluated for their in vitro binding to alpha synuclein (α-syn), beta amyloid (Aβ), and tau fibrils. Compounds with a single double bond in the 3-position had only a modest affinity
A Facile Method for the Synthesis of 3-Alkyloxindole
Du, Tai-Ping,Zhu, Gang-Guo,Zhou, Jian
experimental part, p. 225 - 232 (2012/07/14)
Benzylamine in combination with acetic acid was identified as a powerful catalyst for the condensation of oxindole with aldehydes, acetone or cyclic ketones. A variety of 3-alkyloxindoles could be readily prepared in 10 mmol scale via the sequential benzylamine acetate catalyzed condensation of oxindoles with aldehydes (or ketones) and conjugate reduction by NaBH4.
