ArticleBioorganic & medicinal chemistry letters2011
Discovery and optimization of a novel, selective and brain penetrant M1 positive allosteric modulator (PAM): the development of ML169, an MLPCN probe.
Article in Bioorganic & medicinal chemistry letters, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed.
- Design, synthesis and evaluation of tryptophan analogues as tool compounds to study IDO1 activity.RSC chemical biology · 2021Article
- Alzheimer's Disease Therapeutic Approaches.Advances in experimental medicine and biology · 2020Review
- Biased MScience signaling · 2019Article
- Allosteric Modulation of Class A GPCRs: Targets, Agents, and Emerging Concepts.Journal of medicinal chemistry · 2019Review
- Diverse Effects on MACS chemical neuroscience · 2017Article
- Therapeutics of Neurotransmitters in Alzheimer's Disease.Journal of Alzheimer's disease : JAD · 2017Review
- Prefrontal Cortex-Mediated Impairments in a Genetic Model of NMDA Receptor Hypofunction Are Reversed by the Novel MACS chemical neuroscience · 2016Article
- Further optimization of the M1 PAM VU0453595: Discovery of novel heterobicyclic core motifs with improved CNS penetration.Bioorganic & medicinal chemistry letters · 2016Article
- Application of Parallel Multiparametric Cell-Based FLIPR Detection Assays for the Identification of Modulators of the Muscarinic Acetylcholine Receptor 4 (M4).Journal of biomolecular screening · 2015Article
- Advancing Biological Understanding and Therapeutics Discovery with Small-Molecule Probes.Cell · 2015Review
- Discovery and SAR of muscarinic receptor subtype 1 (M1) allosteric activators from a molecular libraries high throughput screen. Part 1: 2,5-dibenzyl-2H-pyrazolo[4,3-c]quinolin-3(5H)-ones as positive allosteric modulators.Bioorganic & medicinal chemistry letters · 2015Article
- Activation of M1 and M4 muscarinic receptors as potential treatments for Alzheimer's disease and schizophrenia.Neuropsychiatric disease and treatment · 2014Review
- Development of allosteric modulators of GPCRs for treatment of CNS disorders.Neurobiology of disease · 2014Review
- Allosteric modulation of the M1 muscarinic acetylcholine receptor: improving cognition and a potential treatment for schizophrenia and Alzheimer's disease.Drug discovery today · 2013Review
- The Concise Guide to PHARMACOLOGY 2013/14: G protein-coupled receptors.British journal of pharmacology · 2013Article
- Synthesis and SAR studies of 5-(pyridin-4-yl)-1,3,4-thiadiazol-2-amine derivatives as potent inhibitors of Bloom helicase.Bioorganic & medicinal chemistry letters · 2013Article
- Development of M1 mAChR allosteric and bitopic ligands: prospective therapeutics for the treatment of cognitive deficits.ACS chemical neuroscience · 2013Review
- Spirocyclic replacements for the isatin in the highly selective, muscarinic M1 PAM ML137: the continued optimization of an MLPCN probe molecule.Bioorganic & medicinal chemistry letters · 2013Article
- Isatin replacements applied to the highly selective, muscarinic M1 PAM ML137: continued optimization of an MLPCN probe molecule.Bioorganic & medicinal chemistry letters · 2013Article
- The muscarinic M1 receptor positive allosteric modulator PQCA improves cognitive measures in rat, cynomolgus macaque, and rhesus macaque.Psychopharmacology · 2013Article
Corrections and comments
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Authors and funding
13 authors.
Funding
Abstract
This Letter describes a chemical lead optimization campaign directed at VU0108370, a weak M(1) PAM hit with a novel chemical scaffold from a functional HTS screen within the MLPCN. An iterative parallel synthesis approach rapidly established SAR for this series and afforded VU0405652 (ML169), a potent, selective and brain penetrant M(1) PAM with an in vitro profile comparable to the prototypical M(1) PAM, BQCA, but with an improved brain to plasma ratio.
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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.