Table 3.

Biochemical and Cell-based IC₅₀ Values, and Mouse Plasma and Brain Concentrations for 2-position Substitutions Designed to Reduce Polar Surface Area and Molecular Weight^a

compound	R	JNK3 IC50 (µM)	c-jun IC50 (µM)	bpolar surface area	cmouse [plasma]	[µM] [brain]
9a		0.03	0.02	90	2.72	0.15
10a		0.03	nt	77	2.31	0.23
10b		0.06	0.63	68	0.78	1.06
10c		0.17	nt	49	nt	nt
10d		0.09	nt	79	0	0
10e		0.05	0.93	69	nt	nt
10f		0.03	3.0	69	nt	nt

^aJNK3 biochemical IC₅₀ values are the averages of four or more experiments, and the JNK1 and cell-based IC₅₀ values are the averages of two or more experiments. All standard deviations are ≤44 % for the biochemical and ≤81 % for the cell-based assays.

^bPolar surface area calculated by ChemBioDraw Ultra 11.0.

^c10 mg/kg ip 2h.