Format

Send to

Choose Destination
Molecules. 2017 Dec 14;22(12). pii: E2221. doi: 10.3390/molecules22122221.

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

Author information

1
Medicinal Chemistry Research Group, Research Centre for Natural Sciences, Hungarian Academy of Sciences, Magyar tudósok körútja 2, H1117 Budapest, Hungary. kelemen.adam@ttk.mta.hu.
2
Department of Medicinal Chemistry, Institute of Pharmacology, Polish Academy of Sciences, 12 Smętna Street, 31-343 Krakow, Poland. grzegorz.satala@gmail.com.
3
Department of Medicinal Chemistry, Institute of Pharmacology, Polish Academy of Sciences, 12 Smętna Street, 31-343 Krakow, Poland. andrzej.bojarski@gmail.com.
4
Medicinal Chemistry Research Group, Research Centre for Natural Sciences, Hungarian Academy of Sciences, Magyar tudósok körútja 2, H1117 Budapest, Hungary. keseru.gyorgy@ttk.mta.hu.

Abstract

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.

KEYWORDS:

5-HT6R; G-protein coupled receptor; coerulescine; indoline; oxindole

PMID:
29240714
PMCID:
PMC6149751
DOI:
10.3390/molecules22122221
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Multidisciplinary Digital Publishing Institute (MDPI) Icon for PubMed Central
Loading ...
Support Center