G protein‐coupled receptor binding and pharmacological evaluation of indole‐derived thiourea compounds. Issue 2 (29th November 2019)

• Record Type: Journal Article
• Authors: Szulczyk, Daniel; Bielenica, Anna; Kędzierska, Ewa; Leśniak, Anna; Pawłowska, Agata; Bujalska‐Zadrożny, Magdalena; Saccone, Irene; Sparaco, Rosa; Fiorino, Ferdinando; Savchenko, Oleksandra; Struga, Marta
• Is Part Of: Archiv der Pharmazie. Volume 353:Issue 2(2020)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2019-11-29
• Subjects: dopamine receptors -- inverse agonists -- serotonin antagonism -- substituent effect; Pharmaceutical chemistry -- Periodicals; Pharmacology -- Periodicals; 615.19
• DOI: 10.1002/ardp.201900218
• Languages: English
• ISSNs: 0365-6233

Abstract

Abstract: Four 2‐(1 H ‐indol‐3‐yl)ethylthiourea derivatives were prepared by condensation of 2‐(1 H ‐indol‐3‐yl)ethanamine with the corresponding aryl/alkylisothiocyanates in a medium‐polarity solvent. Their structures were confirmed by spectral techniques, and the molecular structure of 3 was determined by X‐ray crystal analysis. For all derivatives, the binding affinities at the 5‐HT2A and 5‐HT2C receptors, as well as their functional activities at the 5‐HT1A and D2 receptors, were determined. The arylthioureas 1 and 4 were the most active at the 5‐HT1A receptor, showing, at the same time, significant selectivity over the studied 5‐HT2 and D2 receptor subtypes. The compounds were tested for their pharmacological activities within the central nervous system in relevant mouse models. The involvement of the serotonergic system in the activity of 1 and 4 was indicated. The antinociceptive action of 4 was linked to its anti‐inflammatory activity. Abstract : A series of indole‐derived thiourea compounds 1–4 were assessed for their 5‐HT1A /5‐HT2A /5‐HT2C /D2 receptor activities in vitro and their pharmacological potency in vivo. The most active benzylthiourea 4 acted as an inverse agonist at the 5‐HT1A receptor, with selectivity over the 5‐HT2 and D2 receptor subtypes