Deepening the Topology of the Translocator Protein Binding Site by Novel N,N-Dialkyl-2-arylindol-3-ylglyoxylamides

作者：Barresi Elisabetta; Bruno Agostino; Taliani Sabrina^*; Cosconati Sandro; Da Pozzo Eleonora; Salerno Silvia; Simorini Francesca; Daniele Simona; Giacomelli Chiara; Marini Anna Maria; La Motta Concettina; Marinelli Luciana; Cosimelli Barbara; Novellino Ettore; Greco Giovanni; Da Settimo Federico; Martini Claudia

来源：Journal of Medicinal Chemistry, 2015, 58(15): 6081-6092.

DOI：10.1021/acs.jmedchem.5b00689

As a continuation of our studies on 2-phenylindol-3-ylglyoxylamides as potent and selective translocator protein (TSPO) ligands, two subsets of novel derivatives, featuring hydrophilic group (OH, NH2, COOH) at the para-position of the pendent 2-phenyl ring (8-16) or different 2-aryl moieties, namely, 3-thienyl, p-biphenyl, 2-naphthyl (23-35), were synthesized and biologically evaluated, some of them showing K-i values in the subnanomolar range and the 2-naphthyl group performance being the best. The resulting SARs confirmed the key role played by interactions taking place between ligands and the lipophilic Li pocket of the TSPO binding site. Docking simulations were performed on the most potent compound of the present series (29) exploiting the recently available 3D structures of TSPO bound to its standard ligand (PK11195). Our theoretical model was fully consistent with SARs of the newly investigated as well of the previously reported 2-phenylindol-3-ylglyoxylamide derivatives.

• 出版日期2015-8-13