| Literature DB >> 26177193 |
Elisabetta Barresi1, Agostino Bruno2, Sabrina Taliani1, Sandro Cosconati3, Eleonora Da Pozzo1, Silvia Salerno1, Francesca Simorini1, Simona Daniele1, Chiara Giacomelli1, Anna Maria Marini1, Concettina La Motta1, Luciana Marinelli2, Barbara Cosimelli2, Ettore Novellino2, Giovanni Greco2, Federico Da Settimo1, Claudia Martini1.
Abstract
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 Ki 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 L1 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.Entities:
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Year: 2015 PMID： 26177193 DOI： 10.1021/acs.jmedchem.5b00689
Source DB: PubMed Journal: J Med Chem ISSN： 0022-2623 Impact factor: 7.446