Table 1.
RSV inhibitory (EC50) and cytotoxic (CC50) concentrations and selectivity indices of 1a and analogs featuring modifications of section A, tested on BEAS-2B human respiratory cells.a
| |||||
|---|---|---|---|---|---|
| Compound No. | R1 | X | EC50 [µM] | CC50 [µM] | SI |
| 1a |
|
C=O | 0.21 (0.14 to 0.3) | 8.3 | 40 |
|
| |||||
| 1b |
|
C=O | 7.1 (6.1 to undef) | ND | ND |
|
| |||||
| 1c |
|
C=O | >10 | ND | ND |
|
| |||||
| 1d |
|
C=O | >10 | ND | ND |
|
| |||||
| 1e |
|
C=O | >10 | ND | ND |
|
| |||||
| 1f |
|
C=O | 0.76 (0.63 to 0.9) | 30 | 39 |
|
| |||||
| 1g |
|
C=O | ~10 | 10 | ND |
|
| |||||
| 1h |
|
C=O | >10 | ND | ND |
|
| |||||
| 1i |
|
C=O | ~10 | ND | ND |
|
| |||||
| 1j |
|
C=O | 5.4 (3.3 to 11.6) | 30 | 6.0 |
|
| |||||
| 1k |
|
C=O | 0.73 (0.61 to 0.88) | 10 | 14 |
|
| |||||
| 1l |
|
C=O | 2.25 (1.13 to 4.5) | 30 | 13 |
|
| |||||
| 1m |
|
C=O | 0.96 (0.64 to 1.45) | 2.6 | 37 |
|
| |||||
| 1n |
|
C=O | >10 | ND | ND |
|
| |||||
| 1o |
|
C=O | >10 | ND | ND |
|
| |||||
| 1p |
|
C=O | >10 | ND | ND |
|
| |||||
| 1q |
|
C=O | >10 | ND | ND |
|
| |||||
| 1r |
|
C=O | >10 | ND | ND |
|
| |||||
| 1s |
|
C=O | >10 | ND | ND |
|
| |||||
| 1t |
|
CH2 | >10 | ND | ND |
|
| |||||
| 1u |
|
SO2 | >10 | ND | ND |
a
Highest concentration assessed for potency calculation was 10 µM, and for cytotoxicity assessment 90 µM. Active concentrations were calculated through four-parameter variable slope regression modeling, values in parentheses specify 95% confidence intervals.
ND: not determined.