305849-40-5Relevant articles and documents
Tozasertib Analogues as Inhibitors of Necroptotic Cell Death
Hofmans, Sam,Devisscher, Lars,Martens, Sofie,Van Rompaey, Dries,Goossens, Kenneth,Divert, Tatyana,Nerinckx, Wim,Takahashi, Nozomi,De Winter, Hans,Van Der Veken, Pieter,Goossens, Vera,Vandenabeele, Peter,Augustyns, Koen
, p. 1895 - 1920 (2018/03/21)
Receptor interacting protein kinase 1 (RIPK1) plays a crucial role in tumor necrosis factor (TNF)-induced necroptosis, suggesting that this pathway might be druggable. Most inhibitors of RIPK1 are classified as either type II or type III kinase inhibitors. This opened up some interesting perspectives for the discovery of novel inhibitors that target the active site of RIPK1. Tozasertib, a type I pan-aurora kinase (AurK) inhibitor, was found to show a very high affinity for RIPK1. Because tozasertib presents the typical structural elements of a type I kinase inhibitor, the development of structural analogues of tozasertib is a good starting point for identifying novel type I RIPK1 inhibitors. In this paper, we identified interesting inhibitors of mTNF-induced necroptosis with no significant effect on AurK A and B, resulting in no nuclear abnormalities as is the case for tozasertib. Compounds 71 and 72 outperformed tozasertib in an in vivo TNF-induced systemic inflammatory response syndrome (SIRS) mouse model.
Base-catalyzed synthesis of aryl amides from aryl azides and aldehydes
Xie, Sheng,Zhang, Yang,Ramstr?m, Olof,Yan, Mingdi
, p. 713 - 718 (2015/12/30)
Aryl amides have been used as important compounds in pharmaceuticals, materials and in molecular catalysis. The methods reported to prepare aryl amides generally require very specific reagents, and the most popular carboxyl-amine coupling reactions demand stoichiometric activators. Herein, we report that aryl azides react with aldehydes under base-catalyzed conditions to yield aryl amides efficiently. Mechanistic investigations support the formation of triazoline intermediates via azide-enolate cycloaddition, which subsequently undergo rearrangement to give amides by either thermal decomposition (20-140 °C) or aqueous acid work-up at room temperature. The strategy does not require nucleophilic anilines and is especially efficient for highly electron-deficient aryl amides, including perfluoroaryl amides, which are otherwise challenging to synthesize.
Synthesis and structure-property relationships of amphiphilic organogelators
Mohmeyer, Nils,Schmidt, Hans-Werner
, p. 4499 - 4509 (2008/02/08)
A series of low-molecular-weight amphiphilic molecules was synthesized and investigated for their ability to gel organic solvents. These amphiphilic molecules are composed of a head-group moiety capable of forming intermolecular associations through hydro
