Table 2.

SAR of substituents of anthranilic acid moiety for ERK5 and LRRK2.

Compound ID	R	Cellular EC50 (ERK5, μM)a	Enzymatic IC50 (ERK5, μM)b	Enzymatic IC50 (LRRK2[G2019S], μM)c
5	R2, R3 = Me, Me	0.19 ± 0.04	0.087 ± 0.007	0.026
16	H, Me	>1.0	1.450 ± 0.210	0.091
17	Me, Et	0.20 ± 0.04	0.066 ± 0.007	0.052
18	Me, i-Pr	0.23 ± 0.03	0.098 ± 0.012	0.36
19	Me, cyclopentyl	0.20 ± 0.04	0.146 ± 0.018	0.781
20	R4 = 4-F	1.32 ± 0.22	0.873 ± 0.060	0.439
21	5-Cl	1.24 ± 0.24	1.130 ± 0.160	1.07
22	4-Cl	11.38 ± 2.04	5.090 ± 0.052	>10
23	5-Me	3.10 ± 0.62	2.460 ± 0.260	0.493
24		0.26 ± 0.04	0.199 ± 0.012	0.005
25		0.08 ± 0.02	0.082 ± 0.009	0.061
26		0.09 ± 0.03	0.162 ± 0.006	0.339

^aThe required concentration for inhibiting 50% of EGF-stimulated autophosphorylation of ERK5 in HeLa cells.

^bThe required concentration for inhibiting 50% of enzymatic activity of ERK5 using an in vitro assay.

^cThe required concentration for inhibiting 50% of enzymatic activity of LRRK2[G2019S] using an in vitro assay.