| Chemical Properties | Back Directory | [Boiling point ]
512.6±50.0 °C(Predicted) | [density ]
1.58±0.1 g/cm3(Predicted) | [form ]
Solid | [pka]
13.42±0.10(Predicted) | [color ]
White to off-white |
| Hazard Information | Back Directory | [Description]
PF-06795071 is a potent and selective covalent MAGL inhibitor with MAGL IC50 = 3 nM; FAAH IC50 = 3.1 μM; log D= 3.8; Cb,u/Cp,u = 1.4. PF-06795071 features a novel trifluoromethyl glycol leaving group which 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 LogD, 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. | [Uses]
PF-06795071 is a potent and selective covalent MAGL inhibitor with an IC50 of 3 nM[1]. | [References]
[1] McAllister LA, et al. Discovery of Trifluoromethyl Glycol Carbamates as Potent and Selective Covalent Monoacylglycerol Lipase (MAGL) Inhibitors for Treatment of Neuroinflammation. J Med Chem. 2018 Apr 12;61(7):3008-3026. DOI:10.1021/acs.jmedchem.8b00070 |
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