Spiro[pyrrolidine-3,3'-oxindoles] as 5-HT7 receptor ligands

Ádám Andor Kelemen; Grzegorz Satała; Andrzej J Bojarski; György M Keserű

doi:10.1016/j.bmcl.2018.06.019

Spiro[pyrrolidine-3,3'-oxindoles] as 5-HT₇ receptor ligands

Bioorg Med Chem Lett. 2018 Aug 1;28(14):2418-2421. doi: 10.1016/j.bmcl.2018.06.019. Epub 2018 Jun 12.

Authors

Ádám Andor Kelemen¹, Grzegorz Satała², Andrzej J Bojarski², György M Keserű³

Affiliations

¹ Medicinal Chemistry Research Group, Research Centre for Natural Sciences, Hungarian Academy of Sciences, Magyar tudósok körútja 2, H3660, 23-3650, 96, 1117 Budapest, Hungary.
² Department of Medicinal Chemistry, Institute of Pharmacology, Polish Academy of Sciences, 12 Smętna Street, 31-343 Krakow, Poland.
³ Medicinal Chemistry Research Group, Research Centre for Natural Sciences, Hungarian Academy of Sciences, Magyar tudósok körútja 2, H3660, 23-3650, 96, 1117 Budapest, Hungary. Electronic address: kelemen.adam@ttk.mta.hu.

PMID: 29910079
DOI: 10.1016/j.bmcl.2018.06.019

Abstract

Here we report the design and synthesis of spiro[pyrrolidine-3,3'-oxindole] derivatives representing a novel scaffold of 5-HT₇ receptor ligands. The synthesized analogues were validated as low nanomolar ligands showing selectivity in a panel of related serotonin receptor subtypes including 5-HT_1AR, 5-HT_2AR and 5-HT₆R.

Keywords: 5-HT(7)R; G-protein coupled receptor; Oxidative spiro-rearrangement; Oxindole; Pharmacophore model.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Dose-Response Relationship, Drug
Ligands
Molecular Structure
Oxindoles / pharmacology*
Receptors, Serotonin / metabolism*
Spiro Compounds / pharmacology*
Structure-Activity Relationship

Substances

Ligands
Oxindoles
Receptors, Serotonin
Spiro Compounds
serotonin 7 receptor
spiro(pyrrolidine-2,3'-oxindole)