1223569-25-2Relevant academic research and scientific papers
Cinnamic anilides as new mitochondrial permeability transition pore inhibitors endowed with ischemia-reperfusion injury protective effect in vivo
Fancelli, Daniele,Abate, Agnese,Amici, Raffaella,Bernardi, Paolo,Ballarini, Marco,Cappa, Anna,Carenzi, Giacomo,Colombo, Andrea,Contursi, Cristina,Di Lisa, Fabio,Dondio, Giulio,Gagliardi, Stefania,Milanesi, Eva,Minucci, Saverio,Pain, Gilles,Pelicci, Pier Giuseppe,Saccani, Alessandra,Storto, Mariangela,Thaler, Florian,Varasi, Mario,Villa, Manuela,Plyte, Simon
, p. 5333 - 5347 (2014/07/08)
In this account, we report the development of a series of substituted cinnamic anilides that represents a novel class of mitochondrial permeability transition pore (mPTP) inhibitors. Initial class expansion led to the establishment of the basic structural requirements for activity and to the identification of derivatives with inhibitory potency higher than that of the standard inhibitor cyclosporine-A (CsA). These compounds can inhibit mPTP opening in response to several stimuli including calcium overload, oxidative stress, and thiol cross-linkers. The activity of the cinnamic anilide mPTP inhibitors turned out to be additive with that of CsA, suggesting for these inhibitors a molecular target different from cyclophylin-D. In vitro and in vivo data are presented for (E)-3-(4-fluoro-3-hydroxy-phenyl)-N-naphthalen-1-yl- acrylamide 22, one of the most interesting compounds in this series, able to attenuate opening of the mPTP and limit reperfusion injury in a rabbit model of acute myocardial infarction.
Acrylamido derivatives useful as inhibitors of the mitochondrial permeability transition
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Page/Page column 49, (2010/05/13)
Acrylamido derivatives useful as therapeutic agents, particularly for the prevention and/or treatment of diseases and conditions associated with the activity of the mitochondrial permeability transition pore (MPTP), such as the diseases characterized by ischemia/reperfusion, oxidative or degenerative tissue damage, are herein described. These compounds belong to the structural formula (I) wherein R, R', R , W and a are as defined in the specification. The invention also relates to the preparation of these compounds, as well as to pharmaceutical compositions comprising them.
