Structure–activity relationships of novel non-competitive mGluR1 antagonists: A potential treatment for chronic pain

A series of novel mGluR1 antagonists have been prepared. Incorporation of fragments derived from weak lead matter into a library led to enhanced potency in a new chemical series. A chemistry driven second library iteration, covering a greatly enhanced area of chemical space, maintained good potency and introduced metabolic stability.

Weakly active (4) was converted into low molecular weight, high activity (29) using library chemistry.Figure optionsDownload as PowerPoint slide