Table 4.

SAR of meta aniline ring substitutions

Compound	R2	R4	Tb IC50,b μM	Hs IC50,c μM	Tb427 EC50,d μM
7	Cl	Cl	3.7 (3.3–4.1)	27% at 180	5.6 (4.5–7.1)
32	Br	Cl	2.2 (2.0–2.4)	33% at 180	4.7 (3.9–5.8)
33	CN	Cl	3.9 (3.2–4.8)	29% at 180	12 (10–14)
34	CF3	Cl	3.9 (3.4–4.4)	39% at 180	13 (11–15)
35	Ph	Cl	3.3 (2.8–3.9)	30% at 63	4.5 (2.1–9.4)
36	SF5	Cl	16 (14–18)	>180	13 (11–15)
37	SF5	Br	8.7 (7.4–10)	>180	0.45 (0.32–0.62)
38	Et	Br	7.6 (5.7–10)	>180	5.5 (4.6–6.6)
39	OEt	Br	6.0 (5.2–6.9)	36% at 180	4.4 (4.2–4.7)
40	OCH2CF3	Br	1.6 (1.1–2.4)	44	4.2 (3.6–4.8)
41	OCH2CHCH2	Br	4.5 (4.1–4.9)	28% at 180	4.4 (3.7–5.3)
42	OBu	Br	4.5 (4.0–5.1)	>180	1.9 (1.7–2.1)
43	OCH2iPr	Br	11 (9.5–12)	>180	4.4 (3.5–5.5)
44	Br	Br	1.9 (1.7–2.1)	31% at 180	4.8 (4.1–5.6)
45	SO2Me	SO2Me	1.5 (1.3–1.7)	39% at 180	>100
46	CF3	CF3	11 (9.8–12)	>180	14 (11–17)
47	OMe	OMe	17 (14–20)	21% at 180	41 (33–51)
48	CO2H	CO2H	>180	>180	>100
49	CO2Me	CO2Me	40% at 180	>180	42 (22–78)
50	Ph	Ph	>180	>180	1.5 (1.3–1.6)
51	N-(3,5-Cl2Ph)−acetamide	N-(3,5-Cl2Ph)−acetamide	>180	>180	2.0 (1.2–3.7)
52	Me	Me	141 (119–167)	>180	19 (17–22)
53	tBu	tBu	>63	>63	4.1 (4.1–4.5)
54	SF5	H	23% at 180	>180	14 (11–17)
55	Cl	H	35% at 180	>180	42 (34–52)
56	Br	H	41% at 180	>180	22 (19–26)
57	F	H	>180	>180	>25
58	SMe	H	149 (122–181)	23% at 180	>25
59	H	H	>180	>180	>25
60	F	F	180 (160–201)	>180	70 (61–80)
61	F	Cl	32 (13–82)	>180	17 (15–20)

All compounds have pK_a(N1)^a of 7.3.

^{a, b, c, d}See footnotes for Table 1.