Table 3.

Modifications to the aniline segment of compound - 1

Cmpd	R1	R2	R3	R4	GAK DSF ΔTm (°C)am	Binding displacement assay Ki (μM)				NAK selectivityb
						GAK	AAK1	BMP2K	STK16
16	H	F	F	F	3.7	0.047	9.5	>100	>100	200
17	H	F	F	H	3.2	0.051	9.6	>100	22	190
18	H	H	F	H	5.6	0.036	8.7	15	19	240
19	H	F	H	H	4.3	0.048	8.4	14	17	180
20	F	H	H	H	3.4	0.086	14	26	6.1	71
21	H	F	Cl	H	4.5	0.056	20	61	39	360
22	H	F	H	Cl	4.2	0.071	28	>100	58	390
23	H	Cl	Cl	H	5.1	0.054	33	>100	>100	390
24	H	H	Cl	H	4.3	0.052	21	64	20	390
25	H	Cl	H	H	4.3	0.050	17	29	26	350
26	Cl	H	H	H	2.8	0.14	13	38	7.4	55
27	H	H	Br	H	3.6	0.13	48	>100	32	250
28	H	Br	H	H	3.8	0.096	24	>100	33	250
29	Br	H	H	H	1.8	0.29	18	40	10	34
30	H	I	H	H	2.6	0.21	35	34	50	160
31	H	H	CN	H	1.7	0.32	1.4	7.6	8.7	4.3
32	H	CN	H	H	1.1	0.46	19	61	9.8	22
33	CN	H	H	H	0.6	0.85	17	25	7.9	9.3
34	H	CF3	H	H	1.3	1.2	>100	>100	52	42
35	H	C≡C	H	H	3.7	0.087	7.1	26	16	82
36	H	Ac	H	H	3.6	0.029	9.1	13	4.7	160
37	H	SO2Me	H	H	0.3	0.97	10	15	1.4	1.4
38	H	H	SO2Me	H	0.2	2.5	14	18	4.5	1.8
39	H	H	OtBu	H	0.3	5.3	4.8	18	35	0.9
40	H	H	CH2SO2CH3	H	0.5	2.4	4.0	14	6.7	1.7

^aAverage of 4 experiments

^bSelectivity relative to the nearest NAK family member