Evidence map›Paper›PMID 40440467›Full record

ArticleChemMedChem2025

Synthesis and Biological Characterization of 4,4-Difluoro-3-(phenoxymethyl)piperidine Scaffold as Dopamine 4 Receptor (D

Saeedeh Saeedi, Sumaiya Nahid, Anish K Vadukoot, Corey R Hopkins

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in ChemMedChem, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

4 authors.

Saeedeh SaeediDepartment of Pharmaceutical Sciences, College of Pharmacy, University of Nebraska Medical Center, Omaha, NE, 68198, USA.
Sumaiya NahidDepartment of Pharmaceutical Sciences, College of Pharmacy, University of Nebraska Medical Center, Omaha, NE, 68198, USA.
Anish K VadukootDepartment of Pharmaceutical Sciences, College of Pharmacy, University of Nebraska Medical Center, Omaha, NE, 68198, USA.
Corey R HopkinsDepartment of Pharmaceutical Sciences, College of Pharmacy, University of Nebraska Medical Center, Omaha, NE, 68198, USA.ORCID https://orcid.org/0000-0003-4958-1697

Funding

Discovery and characterization of selective D4R antagonists and their evaluation in preclinical models of PD-LIDsR01NS119266 · NINDS · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI HOPKINS, COREY R. · 2021 to 2025
$2.3M
NINDS NIH HHS R01 NS119266NINDS NIH HHS R01NS119266
6 · The paper itself

Abstract

The discovery and characterization of a novel series of 4,4-difluoropiperidine ether-based dopamine D4 receptor antagonists are reported. Structure-activity relationship studies lead to the identification of compound 14a, which displays exceptional binding affinity for the D4 receptor (Ki = 0.3 nm) and remarkable selectivity over other dopamine receptor subtypes (>2000-fold vs. D1, D2, D3, and D5). However, compounds in this series are shown to have poor microsomal stability and high plasma protein binding. Despite these limitations, the exceptional selectivity profile of these compounds makes them valuable tool compounds for investigating the D4 receptor signaling in cellular models of L-DOPA-induced dyskinesias. These findings provide important structural insights into the future development of metabolically stable D4 receptor antagonists for therapeutic applications.

Indexed as

Dopamine AntagonistsPiperidinesReceptors, Dopamine D4AnimalsHumansMicrosomes, LiverMolecular StructureStructure-Activity RelationshipDopamine AntagonistsPiperidinesReceptors, Dopamine D4antagonistsdifluoropiperidinedopamine 4 receptorsin vitro PK

Identifiers

PMID40440467
PMCPMC12321283

What OpenQuestion holds

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LicenceCC BY-NC-ND
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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.