ArticleJournal of medicinal chemistry2013
Discovery of the first M5-selective and CNS penetrant negative allosteric modulator (NAM) of a muscarinic acetylcholine receptor: (S)-9b-(4-chlorophenyl)-1-(3,4-difluorobenzoyl)-2,3-dihydro-1H-imidazo[2,1-a]isoindol-5(9bH)-one (ML375).
Article in Journal of medicinal chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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.
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.
Who cites it
25 citing papers in PubMed.
- Article
- Synthesis of Imidazo[2,1-The Journal of organic chemistry · 2025Article
- Targeting the Actions of Muscarinic Receptors on Dopamine Systems: New Strategies for Treating Neuropsychiatric Disorders.Annual review of pharmacology and toxicology · 2024Review
- Modulation of Muscarinic Signalling in the Central Nervous System by Steroid Hormones and Neurosteroids.International journal of molecular sciences · 2022Review
- Discovery of a potent MBioorganic & medicinal chemistry letters · 2022Article
- Unified Approach to Diverse Fused Fragments via Catalytic Dehydrative Cyclization.Chemistry (Weinheim an der Bergstrasse, Germany) · 2022Article
- Multitargeting nature of muscarinic orthosteric agonists and antagonists.Frontiers in physiology · 2022Review
- Acyclic Twisted Amides.Chemical reviews · 2021Review
- Identification of a Novel Allosteric Site at the MACS chemical neuroscience · 2021Article
- Allosteric Molecular Switches in Metabotropic Glutamate Receptors.ChemMedChem · 2021Review
- Current Advances in Allosteric Modulation of Muscarinic Receptors.Biomolecules · 2020Review
- Crystal structure of the MProceedings of the National Academy of Sciences of the United States of America · 2019Article
- Targeting Muscarinic Acetylcholine Receptors for the Treatment of Psychiatric and Neurological Disorders.Trends in pharmacological sciences · 2019Review
- Acute Negative Allosteric Modulation of MACS chemical neuroscience · 2019Article
- Allosteric Modulation of Class A GPCRs: Targets, Agents, and Emerging Concepts.Journal of medicinal chemistry · 2019Review
- Selective inhibition of MAddiction biology · 2018Article
- Discovery and Optimization of Potent and CNS Penetrant MACS chemical neuroscience · 2018Article
- Muscarinic MNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2018Article
- Prediction of consensus binding mode geometries for related chemical series of positive allosteric modulators of adenosine and muscarinic acetylcholine receptors.Journal of computational chemistry · 2017Article
- Structural features embedded in G protein-coupled receptor co-crystal structures are key to their success in virtual screening.PloS one · 2017Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors.
Funding
Abstract
A functional high throughput screen and subsequent multidimensional, iterative parallel synthesis effort identified the first muscarinic acetylcholine receptor (mAChR) negative allosteric modulator (NAM) selective for the M5 subtype. ML375 is a highly selective M5 NAM with submicromolar potency (human M5 IC50 = 300 nM, rat M5 IC50 = 790 nM, M1-M4 IC50 > 30 μM), excellent multispecies PK, high CNS penetration, and enantiospecific inhibition.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.