Description: PF-06795071 is a novel, potent, selective and covalent MAGL (Monoacylglycerol lipase) inhibitor with an IC50 of 3 nM and with en excellent CNS exposure. Monoacylglycerol lipase (MAGL) inhibition provides a potential treatment approach to neuroinflammation through modulation of both the endocannabinoid pathway and arachidonoyl signaling in the central nervous system (CNS). PF-06795071 is a MAGL inhibitor featuring a novel trifluoromethyl glycol leaving group that confers significant physicochemical property improvements as compared with earlier inhibitor series with more lipophilic leaving groups. The design strategy focused on identifying an optimized leaving group that delivers MAGL potency, serine hydrolase selectivity, and CNS exposure while simultaneously reducing log D, improving solubility, and minimizing chemical lability. PF-06795071 achieves excellent CNS exposure, extended 2-AG elevation effect in vivo, and decreased brain inflammatory markers in response to an inflammatory challenge.