Format

Send to

Choose Destination
Chem Cent J. 2018 May 11;12(1):55. doi: 10.1186/s13065-018-0422-5.

Structural determinants influencing halogen bonding: a case study on azinesulfonamide analogs of aripiprazole as 5-HT1A, 5-HT7, and D2 receptor ligands.

Author information

1
Department of Organic Chemistry, Medical University of Silesia, 4 Jagiellońska Street, 41-200, Sosnowiec, Poland. kmarciniec@sum.edu.pl.
2
Department of Medicinal Chemistry, Institute of Pharmacology, Polish Academy of Sciences, 12 Smętna Street, 31-343, Krakow, Poland.
3
Institute of Physics, University of Silesia, 4 Uniwersytecka Street, 40-007, Katowice, Poland.
4
Department of Organic Chemistry, Medical University of Silesia, 4 Jagiellońska Street, 41-200, Sosnowiec, Poland.
5
Department of Medicinal Chemistry, Jagiellonian University Medical College, 9 Medyczna Street, 30-688, Krakow, Poland.

Abstract

A series of azinesulfonamide derivatives of long-chain arylpiperazines with variable-length alkylene spacers between sulfonamide and 4-arylpiperazine moiety is designed, synthesized, and biologically evaluated. In vitro methods are used to determine their affinity for serotonin 5-HT1A, 5-HT6, 5-HT7, and dopamine D2 receptors. X-ray analysis, two-dimensional NMR conformational studies, and docking into the 5-HT1A and 5-HT7 receptor models are then conducted to investigate the conformational preferences of selected serotonin receptor ligands in different environments. The bent conformation of tetramethylene derivatives is found in a solid state, in dimethyl sulfoxide, and as a global energy minimum during conformational analysis in a simulated water environment. Furthermore, ligand geometry in top-scored complexes is also bent, with one torsion angle in the spacer (τ2) in synclinal conformation. Molecular docking studies indicate the role of halogen bonding in complexes of the most potent ligands and target receptors.

KEYWORDS:

Aripiprazole; Azinesulfonamides; Crystal structure; Halogen bond; Long-chain arylpiperazine

Supplemental Content

Full text links

Icon for Springer Icon for PubMed Central
Loading ...
Support Center