AI Article Synopsis
- * Further development and optimization of this compound led to the creation of a much more potent version, VU6022296, with an EC of 32.8 nM and effective central nervous system (CNS) penetration.
- * VU6022296 showed strong, dose-dependent effectiveness in reversing symptoms in a rodent model of Parkinson's disease, specifically in cases of Haloperidol-Induced Catalepsy (HIC). *
Article Abstract
A high throughput screen (HTS) identified a novel, but weak (EC = 6.2 μM, 97% Glu Max) mGlu PAM chemotype based on a 1,4-thiazepane core, VU0544412. Reaction development and chemical optimization delivered a potent mGlu PAM 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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| http://dx.doi.org/10.1016/j.bmcl.2021.127838 | DOI Listing |
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