. Author manuscript; available in PMC: 2021 Jul 9.

Published in final edited form as: J Med Chem. 2020 Jun 17;63(13):7211–7225. doi: 10.1021/acs.jmedchem.0c00463

Table 1.

Antifiloviral Activity of 4-(Aminomethyl)benzamides 5-8and 10-27.

N	Structure	Ebola pseudovirus A549 cells			Marburg pseudovirus A549 cells
N	Structure	% inhibition	EC₅₀^a (μM)	SI^b	% inhibition	EC₅₀^a (μM)

5	X = CH₂; para-	74.0	9.86 ± 2.14	15	90.7	0.53 ± 0.09
6	X = O; para-	57.2	-		68.8	-
7	X = N-Me; para-	29.4	-		30.3	-
8	X = CH₂; meta-	0	-		0	-
9		13.0	-		5.90	-
10		12.9	-		0	-

11	R = 4-CO₂H	3.12	_-		10.3	_-
12	R = 4-SO₂Me	0	-		17.4	-
13	R = 4-SO₂NHMe	0	-		3.30	-
14	R = 4-NHSO₂Me	3.91	-		6.81	-
15	R = 4-CN	0	_-		12.4	_-
16	R = 4-CF₃	89.9	3.87 ± 0.73	9	79.3	5.70 ± 1.56
17	R = 3-CF₃	82.2	2.97 ± 0.20	15	57.5	1.41 ± 0.32
18	R = 3-Cl, 4-CF₃	99.7	2.34 ± 0.57	9	98.5	2.05 ± 0.29
19	R = 3-CF₃, 4-Cl	99.6	1.52 ± 0.28	7	98.2	1.24 ± 0.24
20	R = 3-Cl, 4-SCF₃	99.9	1.27 ± 0.38	5	99.8	1.61 ± 0.15
21	R = 4-cyclo-Pr	74.3	4.57 ± 1.50	22	66.2	2.65 ± 1.64
22	R = 4-i-Pr	93.1	2.87 ± 0.38	10	67.5	2.10 ± 1.24
23	R = 2,4-di-t-Bu	99.5	0.48 ± 0.17	76	85.0	2.34 ± 0.64
24		96.8	0.73 ± 0.29	19	94.0	1.63 ± 0.42
25	R¹ = R² = H	98.1	0.99 ± 0.18	101	73.4	0.96 ± 0.32
26	R¹ = F, R² = H	96.1	0.38 ± 0.12	382	71.0	1.33 ± 1.23
27	R¹ = H, R² = Me	99.3	0.33 ± 0.08	390	88.9	0.85 ± 0.10
	toremifene		0.09 ± 0.04	299

Dose-response studies were conducted to determine EC₅₀ values for those compounds that showed more than 70% inhibition at 12.5 uM concentration; EC₅₀ values were calculated by four-parameter dose-response curve-fitting in GraphPad. Results are from three replicates. Percent inhibition errors are estimated to be <10%; EC₅₀ data are presented as mean ± standard deviation (SD).

Selectivity index is the ratio of CC₅₀/EC₅₀, where CC₅₀ is cytotoxicity assessed by utilizing the “CellTiter 96 aqueous nonradioactive cell proliferation assay” (Promega, Madison, WI).