Peer-reviewed veterinary case report
Discovery and optimization of a novel CNS penetrant series of mGluPAMs based on a 1,4-thiazepane core with in vivo efficacy in a preclinical Parkinsonian model.
- Journal:
- Bioorganic & medicinal chemistry letters
- Year:
- 2021
- Authors:
- Kent, Caitlin N et al.
- Affiliation:
- Vanderbilt University · United States
Abstract
A high throughput screen (HTS) identified a novel, but weak (EC = 6.2 μM, 97% Glu Max) mGluPAM chemotype based on a 1,4-thiazepane core, VU0544412. Reaction development and chemical optimization delivered a potent mGluPAM VU6022296 (EC = 32.8 nM, 108% Glu Max) with good CNS penetration (K = 0.45, K = 0.70) and enantiopreference. Finally, VU6022296 displayed robust, dose-dependent efficacy in reversing Haloperidol-Induced Catalepsy (HIC), a rodent preclinical Parkinson's disease model.
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Search related cases →Original publication: https://pubmed.ncbi.nlm.nih.gov/33556572/