Next Article in Journal
The XFEL Protein Crystallography: Developments and Perspectives
Previous Article in Journal
Charcot-Marie-Tooth: From Molecules to Therapy
Previous Article in Special Issue
Analysis of Expression and Functional Activity of Aromatic L-Amino Acid Decarboxylase (DDC) and Serotonin Transporter (SERT) as Potential Sources of Serotonin in Mouse Ovary
Article Menu

Export Article

Open AccessArticle

The 1,3,5-Triazine Derivatives as Innovative Chemical Family of 5-HT6 Serotonin Receptor Agents with Therapeutic Perspectives for Cognitive Impairment

1
Department of Technology and Biotechnology of Drugs, Medical College, Jagiellonian University, Medyczna 9, PL 30-688 Cracow, Poland
2
Department of Clinical Pharmacy, Medical College, Jagiellonian University, Medyczna 9, PL 30-688 Cracow, Poland
3
Department of Medicinal Chemistry Institute of Pharmacology, Polish Academy of Science, Smętna 12, PL 31-343 Cracow, Poland
4
Department of Pharmacodynamics, Faculty of Pharmacy, Medical College, Jagiellonian University, Medyczna 9, PL 30-688 Cracow, Poland
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(14), 3420; https://doi.org/10.3390/ijms20143420
Received: 27 May 2019 / Revised: 5 July 2019 / Accepted: 7 July 2019 / Published: 12 July 2019
(This article belongs to the Special Issue Serotonin in Health and Disease)
  |  
PDF [3783 KB, uploaded 12 July 2019]
  |  

Abstract

Among serotonin receptors, the 5-HT6 subtype is the most controversial and the least known in the field of molecular mechanisms. The 5-HT6R ligands can be pivotal for innovative treatment of cognitive impairment, but none has reached pharmacological market, predominantly, due to insufficient “druglikeness” properties. Recently, 1,3,5-triazine-piperazine derivatives were identified as a new chemical family of potent 5-HT6R ligands. For the most active triazine 5-HT6R agents found (14), a wider binding profile and comprehensive in vitro evaluation of their drug-like parameters as well as behavioral studies and an influence on body mass in vivo were investigated within this work. Results indicated the most promising pharmacological/druglikeness profiles for 4-((1H-indol-3-yl)methyl)-6-(4-methylpiperazin-1-yl)-1,3,5-triazin-2-amine (3) and 4-((2-isopropyl-5-methylphenoxy)methyl)-6-(4-methylpiperazin-1-yl)-1,3,5-triazin-2-amine (4), which displayed a significant procognitive action and specific anxiolytic-like effects in the behavioral tests in vivo together with satisfied pharmaceutical and safety profiles in vitro. The thymol derivative (4) seems to be of higher importance as a new lead candidate, due to the innovative, non-indole and non-sulfone structure with the best 5-HT6R binding properties. View Full-Text
Keywords: 5-HT6 ligands; 1,3,5-triazine; ADME-Tox parameters; pro-cognitive effects; anxiolytic-like activity 5-HT6 ligands; 1,3,5-triazine; ADME-Tox parameters; pro-cognitive effects; anxiolytic-like activity
Figures

Figure 1

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).

Supplementary material

SciFeed

Share & Cite This Article

MDPI and ACS Style

Latacz, G.; Lubelska, A.; Jastrzębska-Więsek, M.; Partyka, A.; Marć, M.A.; Satała, G.; Wilczyńska, D.; Kotańska, M.; Więcek, M.; Kamińska, K.; Wesołowska, A.; Kieć-Kononowicz, K.; Handzlik, J. The 1,3,5-Triazine Derivatives as Innovative Chemical Family of 5-HT6 Serotonin Receptor Agents with Therapeutic Perspectives for Cognitive Impairment. Int. J. Mol. Sci. 2019, 20, 3420.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Int. J. Mol. Sci. EISSN 1422-0067 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top