Table 1. Structure, Tissue Distribution, FAAH Hydrolysis Rates, and Physicochemical Parameters of the Library of Sobetiramide Prodrugs.

^aR group based on the sobetiramide structure in Figure 1.

^bSynthetic methods as described in Scheme 1.

^cConcentrations expressed as ng sobetirome per gram tissue; data points represent mean ± SEM and n = 3.

^dKinetics of prodrug hydrolysis in COS-7 cell homogenate overexpressing human FAAH, substrate concentration was 100 μM, data points represent mean ± SEM, and n = 3.

^eCalculated using Canvas (Schrödinger).

^fPreviously published in ref (8)