Table 2.

Inhibitory Potency (IC₅₀) and Systemic Distribution of 5-(or 6-)Substituted 3’-carbamoyl-O-biphenyl-3-yl Carbamates.

	R1	R2	In vitro IC50 (nM)a	FAAH inhibition in liver (%)b	FAAH inhibition in brain (%)b	PSA (Å2)d
3	OH	H	2.0	91.7±0.7	−3.0±8.0	83
15	OCH3	H	0.5	94.6±0.7	86.4±2.1	74
21	CH2OH	H	1.2	91.5±1.1	10.5±1.5	83
29	COOH	H	2100	86.3±1.3	−2.1±0.5	94
30 c	OSO3NH4	H	34	84.0±1.2	−11.7±2.6	117
35	H	OH	0.5	89.5±1.1	−4.2±2.5	84
41	H	OCH3	2.0	85.6±2.4	82.6±0.4	74

^aIC₅₀ measured in membrane preparations of Wistar rat brain

^bFAAH inhibition measured ex vivo 1 h after injection in Swiss Webster mice (1 mg/kg, intraperitoneal, n = 3)

^c30 was obtained from 3 upon treatment with SO3-DMF complex in dry DCM (see experimental section for further details)

^dPSA values were calculated using ICM version 3.7 (Molsoft LLC, San Diego, CA).