ArticleBioorganic & medicinal chemistry letters2016
Lead optimization of the VU0486321 series of mGlu(1) PAMs. Part 2: SAR of alternative 3-methyl heterocycles and progress towards an in vivo tool.
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 11 papers.
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Who cites it
11 citing papers in PubMed, 18 citations in OpenAlex.
- Further Optimization of the mGluACS chemical neuroscience · 2025Article
- Discovery of VU6024578/BI02982816: An mGluJournal of medicinal chemistry · 2024Article
- mGluNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2022Article
- Allosteric Modulators of Metabotropic Glutamate Receptors as Novel Therapeutics for Neuropsychiatric Disease.Pharmacological reviews · 2022Review
- mGluCell reports · 2021Article
- Activation of the mGluMolecular psychiatry · 2020Article
- Design and Synthesis ofMolecules (Basel, Switzerland) · 2019Article
- mGlu1 receptor as a drug target for treatment of substance use disorders: time to gather stones together?Psychopharmacology · 2017Review
- Targeting metabotropic glutamate receptors for novel treatments of schizophrenia.Molecular brain · 2017Review
- Re-exploration of the mGlu₁ PAM Ro 07-11401 scaffold: Discovery of analogs with improved CNS penetration despite steep SAR.Bioorganic & medicinal chemistry letters · 2016Article
- Lead optimization of the VU0486321 series of mGlu1 PAMs. Part 3. Engineering plasma stability by discovery and optimization of isoindolinone analogs.Bioorganic & medicinal chemistry letters · 2016Article
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
This Letter describes the further lead optimization of the VU0486321 series of mGlu1 positive allosteric modulators (PAMs), driven by recent genetic data linking loss of function GRM1 to schizophrenia. Steep and caveat-laden SAR plagues the series, but ultimately potent mGlu1 PAMs (EC50s ∼5 nM) have resulted with good DMPK properties (low intrinsic clearance, clean CYP profile, modest Fu) and CNS penetration (Kps 0.25-0.97), along with up to >450-fold selectivity versus mGlu4 and mGlu5.
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Registered trials
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