Evidence map›Paper›PMID 41982735›Full record

ArticleACS medicinal chemistry letters2026

Potent Neuronal Nicotinamide Adenine Dinucleotide-Boosting Tetrahydroquinoxalines: Structure-Activity Relationships and Early Drug Metabolism and Pharmacokinetics Evaluation.

Petra Cuřínová, Melissa Jöe, Filip Cesar, Alan Nicol, Kristián Schwan, Michal Kohout, Carmine Varrichio, Aljona Saleh, Craig E Wheelock, Gauti Jóhannesson and 4 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in ACS medicinal chemistry letters, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing 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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

14 authors.

Petra CuřínováDepartment of Organic Chemistry, University of Chemistry and Technology in Prague, 166 28 Prague, Czech Republic.ORCID https://orcid.org/0000-0001-8264-7032
Melissa JöeDepartment of Clinical Neuroscience, Division of Eye and Vision, St. Erik Eye Hospital, Karolinska Institutet, 171 64 Stockholm, Sweden.
Filip CesarDepartment of Organic Chemistry, University of Chemistry and Technology in Prague, 166 28 Prague, Czech Republic.
Alan NicolDepartment of Clinical Neuroscience, Division of Eye and Vision, St. Erik Eye Hospital, Karolinska Institutet, 171 64 Stockholm, Sweden.
Kristián SchwanDepartment of Organic Chemistry, University of Chemistry and Technology in Prague, 166 28 Prague, Czech Republic.
Michal KohoutDepartment of Organic Chemistry, University of Chemistry and Technology in Prague, 166 28 Prague, Czech Republic.ORCID https://orcid.org/0000-0003-1447-4453
Carmine VarrichioSchool of Pharmacy and Pharmaceutical Sciences, Cardiff University, CF10 3NB Cardiff, U.K.
Aljona SalehDrug Discovery and Development Platform, Science for Life Laboratory, 751 24 Uppsala, Sweden.
Craig E WheelockUnit of Integrative Metabolomics, Institute of Environmental Medicine, Karolinska Institute, 171 77 Stockholm, Sweden.ORCID https://orcid.org/0000-0002-8113-0653
Gauti JóhannessonDepartment of Clinical Neuroscience, Division of Eye and Vision, St. Erik Eye Hospital, Karolinska Institutet, 171 64 Stockholm, Sweden.
Václav EignerInstitute of Physics AS CR v.v.i., 182 00 Prague, Czech Republic.
James R TribbleDepartment of Clinical Neuroscience, Division of Eye and Vision, St. Erik Eye Hospital, Karolinska Institutet, 171 64 Stockholm, Sweden.
Andrea BrancaleDepartment of Organic Chemistry, University of Chemistry and Technology in Prague, 166 28 Prague, Czech Republic.ORCID https://orcid.org/0000-0002-9728-3419
Pete A WilliamsDepartment of Clinical Neuroscience, Division of Eye and Vision, St. Erik Eye Hospital, Karolinska Institutet, 171 64 Stockholm, Sweden.ORCID https://orcid.org/0000-0001-6194-8397

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

We designed and synthesized a series of novel 1,2,3,4-tetrahydroquinoxaline derivatives and evaluated their ability to increase nicotinamide adenine dinucleotide (NAD) levels in primary cortical neurons. Several compounds demonstrated nanomolar potency and enabled the establishment of clear structure-activity relationships (SAR), highlighting key substituents required for activity. Qualitative 3DSAR analysis further identified favorable steric, electrostatic, and hydrophobic features associated with NAD enhancement. Selected lead compounds were assessed for

Indexed as

Neurodegeneration; NAD metabolism; NMNAT2; tetrahydroquinoxaline derivatives

Identifiers

PMID41982735
PMCPMC13071616

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Registered trials

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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.