381229-72-7Relevant academic research and scientific papers
Design, Synthesis,In VitroandIn VivoCharacterization of Selective NKCC1 Inhibitors for the Treatment of Core Symptoms in down Syndrome
Borgogno, Marco,Savardi, Annalisa,Manigrasso, Jacopo,Turci, Alessandra,Portioli, Corinne,Ottonello, Giuliana,Bertozzi, Sine Mandrup,Armirotti, Andrea,Contestabile, Andrea,Cancedda, Laura,De Vivo, Marco
, p. 10203 - 10229 (2021)
Intracellular chloride concentration [Cl-]iis defective in several neurological disorders. In neurons, [Cl-]iis mainly regulated by the action of the Na+-K+-Cl-importer NKCC1 and the K+-Cl-exporter KCC2. Recently, we have reported the discovery of ARN23746 as the lead candidate of a novel class of selective inhibitors of NKCC1. Importantly, ARN23746 is able to rescue core symptoms of Down syndrome (DS) and autism in mouse models. Here, we describe the discovery and extensive characterization of this chemical class of selective NKCC1 inhibitors, with focus on ARN23746 and other promising derivatives. In particular, we present compound 40 ( ARN24092 ) as a backup/follow-up lead within vivoefficacy in a mouse model of DS. These results further strengthen the potential of this new class of compounds for the treatment of core symptoms of brain disorders characterized by the defective NKCC1/KCC2 expression ratio.
MODULATORS OF INTRACELLULAR CHLORIDE CONCENTRATION
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Page/Page column 58-59, (2020/10/19)
The present invention relates to a compound of Formula la, lb and Ic, (Formula Ia) a pharmaceutical composition comprising the same and their use in the treatment or prevention of pathological conditions associated to depolarizing GABAergic transmission including, for example, Down syndrome and autism.
Discovery of novel p-arylthio cinnamides as antagonists of leukocyte function-associated antigen-1/intercellular adhesion molecule-1 interaction. 4. Structure - Activity relationship of substituents on the benzene ring of the cinnamide
Winn,Kester,Von Geldern,Leitza,Devries,Dickinson,Mussatto,Okasinski,Reilly,Liu,Huth,Jae,Freeman,Pei,Xin,Lynch
, p. 4393 - 4403 (2007/10/03)
We have shown that p-arylthio cinnamides can inhibit the interaction of LFA-1 and ICAM-1, which is involved in cell adhesion and the inflammatory process. We now show that 2,3-disubstitution on the aryl portion of the cinnamide results in enhanced activit
