Methods and compositions related to targeting monoacylglycerol lipase
This invention provides compounds that selectively inhibit monoacylglycerol lipase (MAGL). The invention also provides methods of using the MAGL selective inhibitors to stimulate 2-Arachidonoylglycerol (2-AG) mediated endocannabinoid signaling in vivo, and to treat conditions that are associated with or linked to endocannabinoid signaling. The invention additionally provides methods of treating cancer or inhibiting tumor growth by targeting MAGL with MAGL specific inhibitors. The invention further provides methods of screening for MAGL inhibitors with improved biochemical and pharmaceutical properties.
1. A compound of formula I shown below:
wherein X is CH, R 1 is H or OH, and R 2 and R 3 each have the structure
2. The compound of claim 1 , wherein X is CH, R 1 is OH, and R 2 and R 3 each have the structure shown below
3. A method for inhibiting growth of an aggressive tumor cell, comprising contacting the cell with a therapeutically effective amount of a compound of claim 1 , thereby inhibiting growth of the tumor cell.
4. The method of claim 3 , wherein X is CH, R 1 is OH, and R 2 and R 3 each have the structure shown below