Table 1. hRSV CPE Assay Potency, Cytotoxicity, Selectivity Index, and Logarithmic Reduction in Viral Plaques for Analogs with Structural Variations in the (R1) Region of Hit Compound 2.
| entry | cmpd | R1 | RSV CPE potency ± standard deviation EC50 (μM)a | HEp-2 cellular toxicity ± standard deviation CC50 (μM)b | selectivity index (CC50/EC50) | viral titer reduction at 10 μM (log) |
|---|---|---|---|---|---|---|
| 1 | 2 | CH2-4-methylphenyl | 2.1 ± 0.5c | >50.0c | >23.8 | 4.2 |
| 2 | 8 | CH2-2-bromophenyl | >50.0 | 8.2 ± 0.2 | <0.2 | NT |
| 3 | 9 | CH2-3-bromophenyl | 2.2 ± 0.1 | 3.7 ± 0.4 | 1.7 | NT |
| 4 | 10 | CH2-4-bromophenyl | 0.9 ± 0.2 | >50.0 | >55.6 | 4.1 |
| 5 | 11 | CH2-2-fluorophenyl | >50.0 | 7.3 ± 1.0 | <0.2 | NT |
| 6 | 12 | CH2-4-fluorophenyl | 5.1 ± 0.4 | 7.6 ± 0.2 | 1.5 | NT |
| 7 | 13 | CH2-4-chlorophenyl | 6.7 ± 1.9 | >50.0 | >7.5 | 3.1 |
| 8 | 14 | CH2-4-methoxyphenyl | 2.0 ± 0.9 | >50.0 | >25.0 | 2.7 |
| 9 | 15 | CH2-4-nitrophenyl | 0.5 ± 0.05d | >50.0d | >100.0 | 5.6c |
| 10 | 16 | CH2-4-trifluoromethylphenyl | 1.3 ± 0.1 | >50.0 | >38.5 | 2.7 |
| 11 | 17 | CH2-4-nitrilephenyl | 1.3 ± 0.2 | 12.5 ± 1.2 | 7.7 | 4.2 |
| 12 | 18 | CH2-4-ethylphenyl | 1.0 ± 0.05 | >50.0 | >38.5 | 5.9 |
| 13 | 19 | CH2-4-isopropylphenyl | 0.3 ± 0.03c | >50.0c,e | >166.7 | 6.7 |
| 14 | 20 | CH2-5-benzooxadiazole | 4.9 ± 0.7 | >50.0 | >10.2 | 2.1 |
| 15 | 21 | CH2-3-(5-methylisoxazole) | >50.0 | 7.7 ± 0.7 | <0.2 | NT |
| 16 | 22 | CH2-2-pyridyl | >50.0 | 16.0 ± 0.3 | <0.3 | 0.1 |
| 17 | 23 | CH2-3-pyridyl | >50.0 | 8.0 ± 0.3 | <0.2 | 0.9 |
a
Data were averaged from ≥3 experiments.
b
Data were averaged from ≥2 experiments.
c
Data were averaged from two separate compound lots.
d
Data were averaged from three separate compound lots.
e
Data were obtained from a 3-day exposure experiment versus 5-day duration due to precipitation of compound after 3 days. NT = not tested. Data were analyzed using Microsoft Excel 2010.