AI Article Synopsis
- The study focuses on synthesizing new derivatives of 2-phenylindol-3-ylglyoxylamides with hydrophilic groups and different 2-aryl moieties to enhance their effectiveness as translocator protein (TSPO) ligands.
- Biological evaluations showed some compounds demonstrated impressive Ki values in the subnanomolar range, with the 2-naphthyl group being the most effective.
- Docking simulations on the most potent compound provided a theoretical model aligning with structure-activity relationships, affirming the significance of interactions within the TSPO binding site.
Article 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.
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| http://dx.doi.org/10.1021/acs.jmedchem.5b00689 | DOI Listing |
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