New dual ligands for the D2 and 5-HT1A receptors from the group of 1,8-naphthyl derivatives of LCAP

Przemysław Zaręba; Jolanta Jaśkowska; Paweł Śliwa; Grzegorz Satała

doi:10.1016/j.bmcl.2019.06.029

New dual ligands for the D₂ and 5-HT_1A receptors from the group of 1,8-naphthyl derivatives of LCAP

Bioorg Med Chem Lett. 2019 Aug 15;29(16):2236-2242. doi: 10.1016/j.bmcl.2019.06.029. Epub 2019 Jun 20.

Authors

Przemysław Zaręba¹, Jolanta Jaśkowska², Paweł Śliwa², Grzegorz Satała³

Affiliations

¹ Faculty of Chemical Engineering and Technology, Institute of Organic Chemistry and Technology, Cracow University of Technology, 24 Warszawska Street, Cracow 31-155, Poland. Electronic address: pzareba@indy.chemia.pk.edu.pl.
² Faculty of Chemical Engineering and Technology, Institute of Organic Chemistry and Technology, Cracow University of Technology, 24 Warszawska Street, Cracow 31-155, Poland.
³ Department of Medicinal Chemistry, Institute of Pharmacology - Polish Academy of Sciences, 12 Smętna Street, Cracow 31-343, Poland.

PMID: 31253532
DOI: 10.1016/j.bmcl.2019.06.029

Abstract

More than 300 million people are suffering from depression, one of the civilization diseases in the 21st century. Serotonin 5-HT_1AR and dopamine D₂R play an important role in the treatment and pathogenesis of depression. Moreover, in recent years, the efficacy of dual 5-HT_1A/D₂ receptors ligands has been demonstrated in the fight against depression. In this work the new bulky arylpiperazine derivatives (LCAP) were synthesized in microwave radiation field. The affinities for the selected serotonin (5-HT_1A,5-HT_2A,5-HT₆,5-HT₇) and dopamine (D₂) receptors have been evaluated in vitro. Compounds 5.3a, 5.4, 5.1c, 5.3d, 5.2a are promising dual 5-HT_1AR/D₂R ligands. The SAR analysis were additionally supported with molecular docking studies.

Keywords: 5-HT(1A)/D(2); Depression; Microwave-assisted; Molecular modelling; Serotonin receptors.

Publication types

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

MeSH terms

Dopamine D2 Receptor Antagonists / chemical synthesis
Dopamine D2 Receptor Antagonists / chemistry
Dopamine D2 Receptor Antagonists / pharmacology*
Dose-Response Relationship, Drug
Humans
Ligands
Molecular Docking Simulation
Molecular Structure
Piperazine / chemical synthesis
Piperazine / chemistry
Piperazine / pharmacology*
Receptor, Serotonin, 5-HT1A / metabolism*
Receptors, Dopamine D2 / metabolism*
Serotonin Antagonists / chemical synthesis
Serotonin Antagonists / chemistry
Serotonin Antagonists / pharmacology*
Structure-Activity Relationship

Substances

Dopamine D2 Receptor Antagonists
Ligands
Receptors, Dopamine D2
Serotonin Antagonists
Receptor, Serotonin, 5-HT1A
Piperazine