955879-95-5Relevant academic research and scientific papers
The copper-catalyzed aerobic oxidative amidation of tertiary amines
Cheng, Hui-Cheng,Hou, Wen-Jun,Li, Zeng-Wen,Liu, Ming-Yu,Guan, Bing-Tao
supporting information, p. 17596 - 17599 (2015/12/08)
A general and efficient method for the synthesis of tertiary amides has been developed via the copper-catalyzed aerobic oxidative amidation of tertiary amines. Due to the use of the O2 oxidant, various functional groups were well tolerated under the present conditions. Extensive substrates studies demonstrated its potential as a practical approach for the synthesis of tertiary amides.
New flurbiprofen derivatives: Synthesis, membrane affinity and evaluation of in vitro effect on β-amyloid levels
Sozio, Piera,Marinelli, Lisa,Cacciatore, Ivana,Fontana, Antonella,Tuerkez, Hasan,Giorgioni, Gianfabio,Ambrosini, Dario,Barbato, Francesco,Grumetto, Lucia,Pacella, Stephanie,Cataldi, Amelia,Di Stefano, Antonio
, p. 10747 - 10767 (2013/10/22)
Alzheimer′s disease (AD) is characterized by irreversible and progressive loss of memory and cognition and profound neuronal loss. Current therapeutic strategies for the treatment of AD have been directed to a variety of targets with the aim of reversing or preventing the disease but, unfortunately, the available treatments often produce no significant clinical benefits. During the last decades compounds that inhibit or modulate γ-secretase, reducing β amyloid (Aβ) levels, have been considered as potential therapeutics for AD. Among these the (R)-enantiomer of flurbiprofen (FLU) seems to be very promising, but it shows low brain penetration. In this study, in order to improve the properties of FLU against Alzheimer′s pathogenesis we synthesized some novel FLU lipophilic analogues. Lipophilicity of the new molecules has been characterized in terms of clogP, log KC18/W and log K IAM/W values. Permeability has been determined in both gastrointestinal PAMPA (PAMPA-GI) at different pH values and in brain blood barrier PAMPA (PAMPA-BBB) models. They were also tested for their ability to inhibit in vitro γ-secretase activity using rat CTXTNA2 astrocytes. Interestingly, the investigated molecules demonstrated to reduce Aβ 42 levels without affecting the amyloid precursor protein APP level in a clear concentrations-dependent manner.
Novel orally active, dibenzazepinone-based γ-secretase inhibitors
Peters, Jens-Uwe,Galley, Guido,Jacobsen, Helmut,Czech, Christian,David-Pierson, Pascale,Kitas, Eric A.,Ozmen, Laurence
, p. 5918 - 5923 (2008/09/17)
Structural modifications of the γ-secretase inhibitor, LY411575, led to a malonamide analogue (S),(S)-1 with potent inhibitory activity in vitro, but disappointing activity in a mouse model of Alzheimer's disease. Identification and replacement of a metab
