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. 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 3.

Antifiloviral Activity of 4-(Aminomethyl)benzamides 41–50, 52-54and 5-(Aminomethyl)thiophenecarboxamide 55.

N Structure Ebola pseudovirus A549 cells Marburg pseudovirus A549 cells
% inhibition EC50a (μM) SIb % inhibition EC50a (μM)
graphic file with name nihms-1643745-t0009.jpg
41 R1 = R2 = H, R3 = 5-CO2Me 41.7 - 51.2 -
42 R1 = R2 = H, R3 = 5-CF3 56.4 - 49.6 -
43 R1 = R2 = H, R3 = 6-CF3 83.7 1.68 ± 0.43 38 59.2 1.46 ± 0.41
44 R1 = R2 = H, R3 = 6-Cl 81.5 2.22 ± 0.39 14 42.4 2.31 ± 0.37
45 R1 = R2 = H, R3 = 6-F 20.1 - 13.5 -
46 R1 = H, R2 = di-Me, R3 = H 87.3 2.22 ± 1.02 33 21.4 2.90 ± 0.87
47 R1 = H, R2 = cyclo-Pr, R3 = H 74.5 - 34.4 -
48 R1 = Me, R2 = H, R3 = 6-CF3 95.6 1.56 ± 0.69 21 76.9 1.73 ± 0.88
49 R1 = Me, R2 = H, R3 = 5-t-Bu 99.8 2.05 ± 0.33 9 98.1 3.09 ± 0.53
50 R1 = Me, R2 = t-Bu, R3 = H 99.9 0.16 ± 0.07 224 92.8 3.18 ± 1.33
graphic file with name nihms-1643745-t0010.jpg
52 graphic file with name nihms-1643745-t0011.jpg 5.4 - 9.4 -
53 graphic file with name nihms-1643745-t0012.jpg 25.1 - 0 -
54 graphic file with name nihms-1643745-t0013.jpg 0 - 0 -
55 38.9 - 0 -
toremifene 0.09 ± 0.04 299
a

Dose-response studies were conducted to determine EC50 values for those compounds that showed more than 75% 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 ± SD.

b

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).