Deepening the Topology of the Translocator Protein Binding Site by Novel N,N-Dialkyl-2-arylindol-3-ylglyoxylamides
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- 作者：Elisabetta Barresi ; Agostino Bruno ; Sabrina Taliani ; Sandro Cosconati ; Eleonora Da Pozzo ; Silvia Salerno ; Francesca Simorini ; Simona Daniele ; Chiara Giacomelli ; Anna Maria Marini ; Concettina La Motta ; Luciana Marinelli ; Barbara Cosimelli ; Ettore Novellino ; Giovanni Greco ; Federico Da Settimo ; Claudia Martini
- 刊名：Journal of Medicinal Chemistry
- 出版年：2015
- 出版时间：August 13, 2015
- 年：2015
- 卷：58
- 期：15
- 页码：6081-6092
- 全文大小：479K
- ISSN：1520-4804
文摘
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鈥?b>16) or different 2-aryl moieties, namely, 3-thienyl, p-biphenyl, 2-naphthyl (23鈥?b>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.