114361-79-4Relevant academic research and scientific papers
Insights into structure-activity relationships of 3-arylhydrazonoindolin-2-one derivatives for their multitarget activity on β-amyloid aggregation and neurotoxicity
Purgatorio, Rosa,De Candia, Modesto,De Palma, Annalisa,De Santis, Francesco,Pisani, Leonardo,Campagna, Francesco,Cellamare, Saverio,Altomare, Cosimo Damiano,Catto, Marco
, (2018)
Despite the controversial outcomes of clinical trials executed so far, the prevention of β-amyloid (Aβ) deposition and neurotoxicity by small molecule inhibitors of Aβ aggregation remains a target intensively pursued in the search of effective drugs for treating Alzheimer’s disease (AD) and related neurodegeneration syndromes. As a continuation of previous studies, a series of new 3-(2-arylhydrazono)indolin-2-one derivatives was synthesized and assayed, investigating the effects of substitutions on both the indole core and arylhydrazone moiety. Compared with the reference compound 1, we disclosed equipotent derivatives bearing alkyl substituents at the indole nitrogen, and fairly tolerated bioisosteric replacements at the arylhydrazone moiety. For most of the investigated compounds, the inhibition of Aβ40 aggregation (expressed as pIC50) was found to be correlated with lipophilicity, as assessed by a reversed-phase HPLC method, through a bilinear relationship. The N1-cyclopropyl derivative 28 was tested in cell-based assays of Aβ42 oligomer toxicity and oxidative stress induced by hydrogen peroxide, showing significant cytoprotective effects. This study confirmed the versatility of isatin in preparing multitarget small molecules affecting different biochemical pathways involved in AD.
Heterocyclic Systems Containing Bridgehead Nitrogen Atom: Part LX - Synthesis of Thiazolotriazinoindoles
Dahiya, Rajinder,Narayan, Sat,Bindal, Varinder,Kumar, Vinod,Handa, R. N.,Pujari, H. K.
, p. 535 - 538 (2007/10/02)
5-Substituted-isatins (IIa,b), obtained by the reaction of appropriate anilines (Ia,b) with chloral hydrate and hydroxylamine, on condensation with thiosemicarbazide, give isatinthiosemicarbazones (IIIa,b).Compounds IIIa,b on reaction with α-halogenoketones furnish the uncyclized compounds (IVa,b) which on cyclization with phosphoryl chloride afford 1,7-disubstituted thiazolotriazinoindoles (Va,b).Compounds IIIa,b on condensation with 1,2-dibromoethane give 7-substituted 2,3-dihydrothiazolotriazinoindoles (VIa,b).VIa is also obtained from IIIa via VIIa.The structures IV-VI have been established by IR, PMR and mass spectral data.
