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Open AccessFeature PaperArticle

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

1
Medicinal Chemistry Research Group, Research Centre for Natural Sciences, Hungarian Academy of Sciences, Magyar tudósok körútja 2, H1117 Budapest, Hungary
2
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.
Molecules 2017, 22(12), 2221; https://doi.org/10.3390/molecules22122221
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)
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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MDPI and ACS Style

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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