ArticleBioorganic & medicinal chemistry letters2016
Further optimization of the M1 PAM VU0453595: Discovery of novel heterobicyclic core motifs with improved CNS penetration.
Article in Bioorganic & medicinal chemistry letters, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed.
- Drug Design Targeting the Muscarinic Receptors and the Implications in Central Nervous System Disorders.Biomedicines · 2022Review
- Discovery of a novel class of heteroaryl-pyrrolidinones as positive allosteric modulators of the muscarinic acetylcholine receptor MBioorganic & medicinal chemistry letters · 2021Article
- Development of Novel 4-Arylpyridin-2-one and 6-Arylpyrimidin-4-one Positive Allosteric Modulators of the MChemMedChem · 2021Article
- Fine Tuning Muscarinic Acetylcholine Receptor Signaling Through Allostery and Bias.Frontiers in pharmacology · 2020Review
- 6-Phenylpyrimidin-4-ones as Positive Allosteric Modulators at the MACS chemical neuroscience · 2019Article
- MNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2018Article
- Diverse Effects on MACS chemical neuroscience · 2017Article
- Prefrontal Cortex-Mediated Impairments in a Genetic Model of NMDA Receptor Hypofunction Are Reversed by the Novel MACS chemical neuroscience · 2016Article
Corrections and comments
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Authors and funding
12 authors.
Funding
Abstract
This Letter describes the continued chemical optimization of the VU0453595 series of M1 positive allosteric modulators (PAMs). By surveying alternative 5,6- and 6,6-heterobicylic cores for the 6,7-dihydro-5H-pyrrolo[3,4-b]pyridine-5-one core of VU453595, we found new cores that engendered not only comparable or improved M1 PAM potency, but significantly improved CNS distribution (Kps 0.3-3.1). Moreover, this campaign provided fundamentally distinct M1 PAM chemotypes, greatly expanding the available structural diversity for this valuable CNS target, devoid of hydrogen-bond donors.
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Registered trials
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