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Chemical Structure| 62563-07-9 Chemical Structure| 62563-07-9

Structure of 62563-07-9

Chemical Structure| 62563-07-9

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Product Citations

Product Citations

Kim, Ho Young ; Lee, Ji Youn ; Hsieh, Chia-Ju ; Taylor, Michelle ; Luedtke, Robert R ; Mach, Robert H

Abstract: Previous studies have confirmed that the binding of D3 receptor antagonists is competitively inhibited by endogenous dopamine despite excellent binding affinity for D3 receptors. This result urges the development of an alternative scaffold that is capable of competing with dopamine for binding to the D3 receptor. Herein, an SAR study was conducted on metoclopramide that incorporated a flexible scaffold for interaction with the secondary binding site of the D3 receptor. The alteration of benzamide substituents and secondary binding fragments with aryl carboxamides resulted in excellent D3 receptor affinities (Ki = 0.8–13.2 nM) with subtype selectivity to the D2 receptor ranging from 22- to 180-fold. The β-arrestin recruitment assay revealed that 21c with 4-(pyridine-4-yl)benzamide can compete well against dopamine with the highest potency (IC50 = 1.3 nM). Computational studies demonstrated that the high potency of 21c and its analogs was the result of interactions with the secondary binding site of the D3 receptor. These compounds also displayed minimal effects for other GPCRs except moderate affinity for 5-HT3 receptors and TSPO. The results of this study revealed that a new class of selective D3 receptor antagonists should be useful in behavioral pharmacology studies and as lead compounds for PET radiotracer development.

Keywords: D3 receptor antagonists ; metoclopramide ; bitopic ligand ; β-arrestin recruitment assay ; computational chemistry

Alternative Products

Product Details of [ 62563-07-9 ]

CAS No. :62563-07-9
Formula : C6H11BrO2
M.W : 195.05
SMILES Code : BrCCCC1OCCO1
MDL No. :MFCD09868694
InChI Key :IQIXIJRPYSOGPY-UHFFFAOYSA-N
Pubchem ID :357783

Safety of [ 62563-07-9 ]

GHS Pictogram:
Signal Word:Danger
Hazard Statements:H225
Precautionary Statements:P210-P280-P403+P235-P501
Class:3
UN#:1993
Packing Group:
 

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Technical Information

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