A Structure–Activity Analysis of Biased Agonism at the Dopamine D2 Receptor

2013 ◽  
Vol 56 (22) ◽  
pp. 9199-9221 ◽  
Author(s):  
Jeremy Shonberg ◽  
Carmen Klein Herenbrink ◽  
Laura López ◽  
Arthur Christopoulos ◽  
Peter J. Scammells ◽  
...  
Keyword(s):  
Dopamine D2 Receptor ◽  
D2 Receptor ◽  
Activity Analysis ◽  
Biased Agonism ◽  
Dopamine D2 ◽  
Structure Activity

scholarly journals Novel Bivalent Ligands Based on the Sumanirole Pharmacophore Reveal Dopamine D2 Receptor (D2R) Biased Agonism

2017 ◽  
Vol 60 (7) ◽  
pp. 2890-2907 ◽  
Author(s):  
Alessandro Bonifazi ◽  
Hideaki Yano ◽  
Michael P. Ellenberger ◽  
Ludovic Muller ◽  
Vivek Kumar ◽  
...  
Keyword(s):  
Dopamine D2 Receptor ◽  
D2 Receptor ◽  
Bivalent Ligands ◽  
Biased Agonism ◽  
Dopamine D2

An attempt at the hydrated imidazoline ring expansion (HIRE) of diarene-fused [1,4]diazepinones delivers selective dopamine D2 receptor ligands

Synthesis ◽  
2021 ◽  
Author(s):  
Sergey Grintsevich ◽  
Alexander V. Sapegin ◽  
Andrzej Bojarski ◽  
Beata Duszyńska ◽  
Mikhail Krasavin
Keyword(s):  
Dopamine D2 Receptor ◽  
D2 Receptor ◽  
Ring Expansion ◽  
Side Chain ◽  
Receptor Ligands ◽  
Structure Activity Relationships ◽  
Dopamine D2 ◽  
Structure Activity ◽  
Imidazoline Ring ◽  
Selective Dopamine

Attempts to extend the hydrated imidazoline ring expansion (HIRE) strategy to a series of diarene-fused [1,4]diazepinones (earlier applied successfully to bis-pyrido substrate nevirapine) resulted in no ring expansion but rather 2-aminoethyl side chain expulsion. This seeming setback (setting the limitations to the HIRE methodology substrate scope) led to the discovery of selective dopamine D2 ligands with elements of structure-activity relationships.

scholarly journals The Universal 3D QSAR Model for Dopamine D2 Receptor Antagonists

2019 ◽  
Vol 20 (18) ◽  
pp. 4555 ◽  
Author(s):  
Agata Zięba ◽  
Justyna Żuk ◽  
Damian Bartuzi ◽  
Dariusz Matosiuk ◽  
Antti Poso ◽  
...  
Keyword(s):  
Dopamine D2 Receptor ◽  
D2 Receptor ◽  
3D Qsar ◽  
Qsar Model ◽  
Structure Activity Relationship ◽  
Activity Relationship ◽  
Receptor Antagonists ◽  
Comfa Model ◽  
Dopamine D2 ◽  
Structure Activity

In order to search for novel antipsychotics acting through the D2 receptor, it is necessary to know the structure–activity relationships for dopamine D2 receptor antagonists. In this context, we constructed the universal three-dimensional quantitative structure–activity relationship (3D- QSAR) model for competitive dopamine D2 receptor antagonists. We took 176 compounds from chemically different groups characterized by the half maximal inhibitory concentration (IC50)from the CHEMBL database and docked them to the X-ray structure of the human D2 receptor in the inactive state. Selected docking poses were applied for Comparative Molecular Field Analysis (CoMFA) alignment. The obtained CoMFA model is characterized by a cross-validated coefficient Q2 of 0.76 with an optimal component of 5, R2 of 0.92, and an F value of 338.9. The steric and electrostatic field contributions are 67.4% and 32.6%, respectively. The statistics obtained prove that the CoMFA model is significant. Next, the IC50 of the 16 compounds from the test set was predicted with R2 of 0.95. Finally, a progressive scrambling test was carried out for additional validation. The CoMFA fields were mapped onto the dopamine D2 receptor binding site, which enabled a discussion of the structure–activity relationship based on ligand–receptor interactions. In particular, it was found that one of the desired steric interactions covers the area of a putative common allosteric pocket suggested for some other G protein-coupled receptors (GPCRs), which would suggest that some of the known dopamine receptor antagonists are bitopic in their essence. The CoMFA model can be applied to predict the potential activity of novel dopamine D2 receptor antagonists.

Effect of amphetamine on dopamine D2 receptor binding in the primate brain with the agonist ligand [11C]MNPA

2005 ◽  
Vol 25 (1_suppl) ◽  
pp. S646-S646
Author(s):  
Nicholas Seneca ◽  
Sjoerd Finnema ◽  
Masanori Ichise ◽  
Balazs Gulyas ◽  
Håkan Wikstrom ◽  
...  
Keyword(s):  
Receptor Binding ◽  
Dopamine D2 Receptor ◽  
D2 Receptor ◽  
Dopamine D2 ◽  
Primate Brain
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