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

Chemistry Central Journal
Krzysztof MarciniecPaweł Zajdel

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.

References

May 17, 2001·Bioorganic & Medicinal Chemistry Letters·T NishimuraM Sunagawa
Apr 1, 2003·Journal of Computational Chemistry·Maurizio CossiVincenzo Barone
Jun 5, 2003·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·David A ShapiroRichard Mailman
Jul 21, 2005·Current Medicinal Chemistry·G CaliendoF Fiorino
Aug 24, 2011·Journal of Medicinal Chemistry·Balázs VolkGábor Szénási
Aug 7, 2012·Journal of Computer-aided Molecular Design·Rainer WilckenFrank M Boeckler
Nov 14, 2012·Journal of Medicinal Chemistry·Rainer WilckenFrank M Boeckler
Dec 24, 2013·Future Medicinal Chemistry·Pawel ZajdelAnna Wesolowska
Jan 9, 2015·Acta Crystallographica. Section C, Structural Chemistry·George M Sheldrick
Jan 9, 2015·Acta Crystallographica. Section C, Structural Chemistry·Anthony L Spek
Nov 20, 2015·Journal of Chemical Theory and Computation·Edward HarderRichard A Friesner
Jan 16, 2016·The European Physical Journal. C, Particles and Fields·G AadUNKNOWN ATLAS Collaboration
Oct 30, 2016·Postgraduate Medicine·Hani Raoul Khouzam
Apr 1, 2017·Acta Crystallographica Section B, Structural Science, Crystal Engineering and Materials·Rafał Kurczab

❮ Previous
Next ❯

Citations

May 28, 2019·Expert Opinion on Drug Discovery·Paulo J CostaDiogo Vila-Viçosa
Sep 6, 2018·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Magda KondejAgnieszka A Kaczor
Jul 14, 2021·Future Medicinal Chemistry·Agnieszka JankowskaGrażyna Chłoń-Rzepa

❮ Previous
Next ❯

Methods Mentioned

BETA
nuclear magnetic resonance
NMR
X-ray
column chromatography

Software Mentioned

OPLS3
Gaussian
SHELXL
Schrödinger Suite
Prime
Bruker
Jmol
Epik
AFIX
CrysAlisPro

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.