Table 4.

Modifications to the quinoline core of compound - 1

Cmpd	R1	R2	R3	GAK DSF ΔTm (°C)a	Binding displacement assay Ki (μM)				NAK selectivityb	NanoBRETc
					GAK	AAK1	BMP2K	STK16		GAK IC50 (nM)
1	H	CF3	H	6.3	0.0039	54	>100	17	4300	180
41	H	H	H	4.4	0.040	>100	>100	>100	>2500	780
42	H	F	H	5.9	0.0057	83	>100	>100	14000	270
43	H	H	F	5.8	0.0024	44	>100	>100	18000	510
44	F	H	F	3.1	0.14	>100	>100	>100	>720	4400
45	H	tBu	H	5.2	0.0081	>100	>100	68	8400	330
46	H	CN	H	4.4	0.0015	16	16	2.5	11000	350
47	H	SO2Me	H	3.3	0.018	73	>100	61	3400	3100
48	H	OMe	H	6.0	0.013	>100	>100	>100	>7700	280
49	H	OMe	OMe	8.8	0.00054	28	63	>100	51000	25
50	H	H	OMe	6.1	0.0026	58	>100	>100	22000	440
51	H	H	CF3	5.6	0.0062	90	>100	>100	15000	520
52	H	H	CN	5.3	0.0027	67	>100	25	9300	340

^aAverage of 4 experiments

^bSelectivity relative to the nearest NAK family member

^cAverage of 2 experiments