ArticleACS medicinal chemistry letters2010
Novel N-Substituted Benzimidazolones as Potent, Selective, CNS-Penetrant, and Orally Active M1 mAChR Agonists.
Article in ACS medicinal chemistry letters, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
What it found
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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
24 citing papers in PubMed, 55 citations in OpenAlex.
- Trial
- The novel orthosteric agonist M1 muscarinic acetylcholine receptor reveals anti-Alzheimer's disease activity.Scientific reports · 2024Article
- A golden age of muscarinic acetylcholine receptor modulation in neurological diseases.Nature reviews. Drug discovery · 2024Review
- The methodology for preparing domperidone: strategies, routes and reaction processes.RSC advances · 2022Review
- MPharmacology research & perspectives · 2022Article
- Intrahippocampal blockade of nicotinic or muscarinic receptors fails to impair nonnavigational spatial memory in macaques.Behavioral neuroscience · 2021Article
- Preparation of a FirstMolecules (Basel, Switzerland) · 2020Article
- Biased M1-muscarinic-receptor-mutant mice inform the design of next-generation drugs.Nature chemical biology · 2020Article
- Assessing and improving the performance of consensus docking strategies using the DockBox package.Journal of computer-aided molecular design · 2019Article
- Designing Hybrids Targeting the Cholinergic System by Modulating the Muscarinic and Nicotinic Receptors: A Concept to Treat Alzheimer's Disease.Molecules (Basel, Switzerland) · 2018Review
- Optimization of a Series of Mu Opioid Receptor (MOR) Agonists with High G Protein Signaling Bias.Journal of medicinal chemistry · 2018Article
- Bitopic Binding Mode of an MMolecular pharmacology · 2018Article
- Article
- Article
- Acetylcholine modulates gamma frequency oscillations in the hippocampus by activation of muscarinic M1 receptors.The European journal of neuroscience · 2017Article
- Synthesis and Antitumor Evaluation of Novel 5-Hydrosulfonyl-1H-benzo[d]imidazol-2(3H)-one Derivatives.Molecules (Basel, Switzerland) · 2016Article
- Activation of Muscarinic M1 Acetylcholine Receptors Induces Long-Term Potentiation in the Hippocampus.Cerebral cortex (New York, N.Y. : 1991) · 2016Article
- An evaluation of the brain distribution of [(11)C]GSK1034702, a muscarinic-1 (M 1) positive allosteric modulator in the living human brain using positron emission tomography.EJNMMI research · 2014Article
- Molecular mechanisms of bitopic ligand engagement with the M1 muscarinic acetylcholine receptor.The Journal of biological chemistry · 2014Article
- Computational methods in drug discovery.Pharmacological reviews · 2014Review
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 at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Virtual screening of the corporate compound collection yielded compound 1 as a subtype selective muscarinic M1 receptor agonist hit. Initial optimization of the N-capping group of the central piperidine ring resulted in compounds 2 and 3 with significantly improved potency and selectivity. Subsequent optimization of substituents on the phenyl ring of the benzimidazolone moiety led to the discovery of novel muscarinic M1 receptor agonists 4 and 5 with excellent potency, general and subtype selectivity, and pharmacokinetic (PK) properties including good central nervous system (CNS) penetration and oral bioavailability. Compound 5 showed robust in vivo activities in animal models of cognition enhancement. The combination of high potency, excellent selectivity, and good PK properties makes compounds 4 and 5 valuable tool compounds for investigating and validating potential therapeutic benefits resulting from selective M1 activation.
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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.