mGlu₅ negative allosteric modulators: a patent review (2013 - 2016).

Area of Science:

• Neuroscience
• Medicinal Chemistry

Background:

• Small molecule mGlu5 NAMs are investigated for psychiatric and neurodegenerative disorders.
• Clinical trials have advanced for Fragile X Syndrome (FXS), Parkinson's disease with Леводопа-induced dyskinesia (PD-LID), and Major Depressive Disorder (MDD).

Purpose of the Study:

• To review clinical advancements of mGlu5 NAMs.
• To summarize patent applications for mGlu5 NAMs filed since 2013.
• To categorize new chemical entities based on structural similarity to existing compounds.

Main Methods:

• Review of clinical trial data.
• Analysis of patent literature from 2013 onwards.
• Classification of novel small molecules by chemotype.

Main Results:

• Clinical trial outcomes have presented challenges, tempering initial optimism.
• Recent patent filings include improved existing compounds and novel small molecules.
• New compounds encompass both traditional disubstituted alkyne structures and diverse alternative chemotypes.

Conclusions:

• Despite recent clinical disappointments, research into mGlu5 NAMs remains active.
• A wide array of chemical structures are now available for further investigation.
• Continued exploration of these diverse mGlu5 NAMs may lead to future therapeutic breakthroughs.