Evidence map›Paper›PMID 39737720›Full record

ArticleArchiv der Pharmazie2025

Piperazine-based P2X4 receptor antagonists.

Katharina Sophie Erlitz, Alena I Siutkina, Ann-Kathrin Prinz, Oliver Koch, Dmitrii V Kalinin, Anna Junker

Abstract read
In one paragraph

Article in Archiv der Pharmazie, 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

6 authors.

Katharina Sophie ErlitzEuropean Institute for Molecular Imaging (EIMI), University of Muenster, Muenster, Germany.
Alena I SiutkinaInstitut für Pharmazeutische und Medizinische Chemie der Universität Münster, Muenster, Germany.
Ann-Kathrin PrinzInstitut für Pharmazeutische und Medizinische Chemie der Universität Münster, Muenster, Germany.
Oliver KochInstitut für Pharmazeutische und Medizinische Chemie der Universität Münster, Muenster, Germany.ORCID http://orcid.org/0000-0001-9228-217X
Dmitrii V KalininInstitut für Pharmazeutische und Medizinische Chemie der Universität Münster, Muenster, Germany.
Anna JunkerEuropean Institute for Molecular Imaging (EIMI), University of Muenster, Muenster, Germany.ORCID http://orcid.org/0000-0001-5151-0930

Funding

German Research Foundation (DFG) EXC 2180-390900677German Research Foundation (DFG) GRK2515/1-1German Research Foundation (DFG) JU 2966/2-1
6 · The paper itself

Abstract

The P2X4 receptor (P2X4R), a ligand-gated ion channel activated by ATP, plays a critical role in neuroinflammation, chronic pain, and cancer progression, making it a promising therapeutic target. In this study, we explored the design and synthesis of piperazine-based P2X4R antagonists, building on the structural framework of paroxetine. A series of over 35 compounds were synthesized to investigate structure-activity relationships (SARs) in a Ca²⁺-flux assay for P2X4R antagonistic activity. Several compounds outperformed paroxetine in terms of antagonistic P2X4R potency. Further studies on absorption, distribution, metabolism, excretion properties revealed that increased lipophilicity often correlated with high plasma protein binding and decreased metabolic stability, particularly in compounds with a naphthalene-2-yloxy group. Although promising SARs were observed, further optimization is needed to enhance antagonistic P2X4R receptor activity. This work provides important insights into the development of piperazine-based P2X4R antagonists and lays the foundation for future therapeutic advancements targeting P2X4R-related diseases.

Indexed as

PiperazinesPurinergic P2X Receptor AntagonistsReceptors, Purinergic P2X4AnimalsDose-Response Relationship, DrugHumansMolecular StructurePiperazineStructure-Activity RelationshipPiperazinePiperazinesPurinergic P2X Receptor AntagonistsReceptors, Purinergic P2X4Buchwald reactionCham‐Evans‐Lam couplingligand‐gated ion channelP2X4R antagonistP2X4 receptor

Identifiers

PMID39737720
PMCPMC11686045

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

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 Socratic graph.