Table 10.

IC₅₀ determination of trisubstituted derivatives.

Compd.	R1	R2	R3	R4	IC50 [nM]
					KITWT	KITV559D/T670I	KITV559D/V654A	KITD816H
70a	I	CF3	H	CH3	6.8 ± 21	a	a	a
70b	H	CF3	F	CH3	555.7 ± 41.6	a	a	a
70c	I	CF3	Et	CH3	1039.3 ± 513.9	a	a	a
70d	I	CF3	F	CH3	183.7 ± 186.5	a	a	a
71a	H	CF3	H	CH3	230.7 ± 1.2	a	a	a
71b		CF3	H	CH3	3.5 ± 0.6	116 ± 20.1	a	a
71c		CF3	H	CH3	120.9 ± 154.7	a	a	a
71d		CF3	H	CH3	6.7 ± 1.9	158.7 ± 43	a	a
71e		CF3	H	CH3	2.1 ± 0.6	24 ± 3.1	1101.6 ± 47.8	137.6 ± 2.3
71f		CF3	H	CH3	5.8 ± 0.2	150.2 ± 35.3	a	2267.8 ± 105.3
71g		CF3	H	CH3	1.9 ± 0.6	21.4 ± 1.2	246.6 ± 71.2	42.2 ± 13.0
71h		CF3	H	CH3	3.3 ± 0.9	106.8 ± 7.2	252.5 ± 13.2	2614.3 ± 745.4
71i		CF3	H	CH3	1.6 ± 0.9	72.0 ± 5.2	a	a
71j		CF3	H	CH3	2 ± 0.5	29.8 ± 1.4	777.2 ± 88.6	99.3 ± 43.3
71k		CF3	H	CH3	2.5 ± 0.9	2147.2 ± 213.1	a	a
71l		CF3	H	CH3	2.0 ± 0.6	28.8 ± 1.3	908.3 ± 165.0	140 ± 13.4
71m		CF3	H	CH3	4 ± 0	18.2 ± 6.8	313.5 ± 132.2	104.3 ± 8.7
71n		H	H	CH3	239.6 ± 307.6	a	a	a
71o		H	H	CH3	3.3 ± 1.8	a	a	a
71p		H	H	CH3	100.3 ± 84.2	a	a	a
71q		H	H	CH3	2.6 ± 1.0	a	a	a
71r		F	H	CH3	2.3 ± 0.5	a	a	a
71s		F	H	CH3	6.5 ± 1.1	a	a	1706.6 ± 803.4
71t		CF3	CH3	H	6.2 ± 2.3	21 ± 3.6	1084.7 ± 304.0	325.8 ± 111.1
Ponatinib					1.7 ± 0.7	17.4 ± 9.8	136.0 ± 39.9	20 ± 2.2

^a No inhibition.