English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

The pharmacology of the M 5 muscarinic acetylcholine receptor (mAChR) is the least understood of the five mAChR subtypes due to a historic lack of selective small molecule tools. To address this shortcoming, we have continued the optimization effort around the prototypical M 5 positive allosteric modulator (PAM) ML380 and have discovered and optimized a new series of M 5 PAMs based on a chiral N-(indanyl)piperidine amide core with robust SAR, human and rat M 5 PAM EC 50 values &lt;100 nM and rat brain/plasma K p values of ∼0.40. Interestingly, unlike M 1 and M 4 PAMs with unprecedented mAChR subtype selectivity, this series of M 5 PAMs displayed varying degrees of PAM activity at the other two natively G q -coupled mAChRs, M 1 and M 3 , yet were inactive at M 2 and M 4 .

acs chemical neuroscience

Discovery and Optimization of Potent and CNS Penetrant M<sub>5</sub>-Preferring Positive Allosteric Modulators Derived from a Novel, Chiral <i>N</i>-(Indanyl)piperidine Amide Scaffold

Discovery and Optimization of Potent and CNS Penetrant M5-Preferring Positive Allosteric Modulators Derived from a Novel, Chiral N-(Indanyl)piperidine Amide Scaffold

Discovery and Optimization of Potent and CNS Penetrant M₅-Preferring Positive Allosteric Modulators Derived from a Novel, Chiral N-(Indanyl)piperidine Amide Scaffold