107583-34-6Relevant 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
, (2018/07/13)
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.
A palladium-catalyzed synthesis of isatins (1H-Indole-2,3-diones) from 1-(2-haloethynyl)-2-nitrobenzenes
S?derberg, Bj?rn C.G.,Gorugantula, Sobha P.,Howerton, Chet R.,Petersen, Jeffrey L.,Dantale, Shubhada W.
experimental part, p. 7357 - 7363 (2009/12/04)
An inherently regiospecific synthesis of isatins (1H-indole-2,3-diones) starting from 1-halo-2-nitrobenzenes is described. The isatins are formed by an intramolecular palladium-catalyzed annulation of 2-(2-haloethynyl)-1-nitrobenzenes via the formation of 2-haloisatogens.
Synthesis of substituted quinoline-4-carboxylic acids
Lackey,Sternbach
, p. 993 - 997 (2007/10/02)
A high yielding synthesis of a variety of quinoline-4-carboxylic acids has been accomplished using a modified Pfitzinger approach involving the condensation of a ketone with an isatin derivative employing aqueous acid conditions. A convenient synthesis of
Biological activities and quantitative structure-activity relationships of spiro[imidazolidine-4,4'(1'H)-quinazoline]-2,2',5(3'H)-triones as aldose reductase inhibitors
Yamagishi,Yamada,Ozaki,Asao,Shimizu,Suzuki,Matsumoto,Matsuoka,Matsumoto
, p. 2085 - 2094 (2007/10/02)
A series of spiro[imidazolidine-4,4'(1'H)-quinazoline]-2,2',5(3'H)-triones were prepared and tested for aldose reductase inhibitory activity. The 6'- halogenated derivatives were found to be highly potent in vitro inhibitors of male rabbit lens aldose reductase and in vivo inhibitors of polyol accumulation in the sciatic nerves of galactosemic rats. Of these, (4R)-6'- chloro-3'-methylspiro[imidazolidine-4,4'(1'H)-quinazoline]-2,2',5(3'H)-trione (67) showed the most potent in vitro and in vivo activities. An oral dose of 3 g/kg of compound 67 caused neither death nor behavioral abnormality in the preliminary acute toxicity study using mice and rats. Compound 67 was selected as a candidate for further evaluation. The quantitative structure- activity relationships in this series are also discussed.
