mGlu₅ negative allosteric modulators: a patent review (2010 – 2012)

Abstract

Introduction: The design and development of small molecule negative allosteric modulators (NAMs) of the metabotropic glutamate receptor subtype 5 (mGlu₅) has been an area of intense interest for over a decade. Potential roles have been established for mGlu₅ NAMs in the treatment of diseases such as pain, anxiety, gastroesophageal reflux disease (GERD), Parkinson's disease levodopa-induced dyskinesia (PD-LID), fragile X syndrome (FXS), autism, addiction, and depression.

Areas covered: This review begins with an update of the clinical trial efforts with mGlu₅ NAMs. Following that update, the review summarizes small molecule mGlu₅ NAM patent applications published between 2010 and 2012. These summaries are subdivided into three separate groups: inventions related to improvements in drug properties and/or developability, new chemical entities that contain a disubstituted alkyne, and new chemical entities that do not contain a disubstituted alkyne.

Expert opinion: Given the abundant promise found within the mGlu₅ NAM field, optimism remains that a drug will emerge from this therapeutic class. Still, the launch of a new drug is far from a certainty. It is encouraging to observe the ever-increasing chemical diversity among mGlu₅ NAMs. Finally, in spite of the mature nature of this field, room remains for new advancements.

Keywords::

• dipraglurant
• dyskinesia
• fragile X syndrome
• glutamate
• mavoglurant
• mGlu₅
• negative allosteric modulator
• neuroscience
• Parkinson's disease
• RG7090

Notes

This box summarizes key points contained in the article.