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Molecules 2017, 22(12), 2221;

Spiro[pyrrolidine-3,3′-oxindoles] and Their Indoline Analogues as New 5-HT6 Receptor Chemotypes

Medicinal Chemistry Research Group, Research Centre for Natural Sciences, Hungarian Academy of Sciences, Magyar tudósok körútja 2, H1117 Budapest, Hungary
Department of Medicinal Chemistry, Institute of Pharmacology, Polish Academy of Sciences, 12 Smętna Street, 31-343 Krakow, Poland
Author to whom correspondence should be addressed.
Received: 1 November 2017 / Revised: 11 December 2017 / Accepted: 12 December 2017 / Published: 14 December 2017
(This article belongs to the Special Issue Advances in Spiro Compounds)
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Synthetic derivatives of spiro[pyrrolidinyl-3,3′-oxindole] alkaloids (coerulescine analogues) were investigated as new ligands for aminergic G-protein coupled receptors (GPCRs). The chemical starting point 2′-phenylspiro[indoline-3,3′-pyrrolidin]-2-one scaffold was identified by virtual fragment screening utilizing ligand- and structure based methods. As a part of the hit-to-lead optimization a structure-activity relationship analysis was performed to explore the differently substituted 2′-phenyl-derivatives, introducing the phenylsulphonyl pharmacophore and examining the corresponding reduced spiro[pyrrolidine-3,3′-indoline] scaffold. The optimization process led to ligands with submicromolar affinities towards the 5-HT6 receptor that might serve as viable leads for further optimization. View Full-Text
Keywords: oxindole; indoline; coerulescine; 5-HT6R; G-protein coupled receptor oxindole; indoline; coerulescine; 5-HT6R; G-protein coupled receptor

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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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Kelemen, Á.A.; Satala, G.; Bojarski, A.J.; Keserű, G.M. Spiro[pyrrolidine-3,3′-oxindoles] and Their Indoline Analogues as New 5-HT6 Receptor Chemotypes. Molecules 2017, 22, 2221.

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