Table 2.
Antiviral Activity of Compounds against Wild-Type and MDR HIV-1 Strainsa
 | ||||||||
|---|---|---|---|---|---|---|---|---|
| Compd. | R1 | R2 | EC50 (nM) (fold change) |
|||||
| WT | WT-A | WT-B | WT-C | MDR1 | MDR | |||
| 15d | H | 3,4-S-C=N- | 21.5 | 29.8 | 14.1 | 40.9 | 112.9 (5) | 123.1 (6) |
| 24d | 3-CF3 | 3,4-S-C=N- | 13.5 | 16.1 | 9.9 | 32.5 | 57.6 (4) | 53.4 (4) |
| 25d | 3-OCF3 | 3,4-S-C=N- | 22.1 | 32.5 | 12.7 | 57.8 | 104.5 (5) | 110.8 (5) |
| 26d | 3-Ac | 3,4-S-C=N- | 6.5 | 9.7 | 4.2 | 10.1 | 32.3 (5) | 34.7 (5) |
| 27b | 3-SO2CH3 | 4-OCH3 | 5.5 | 7.3 | 4.7 | 9.6 | 14.4 (3) | 18.6 (3) |
| 27c | 3-SO2CH3 | 3,4-OCH2O- | 4.0 | 7.8 | 3.5 | 7.6 | 13.6 (3) | 12.1 (3) |
| 27d | 3-SO2CH3 | 3,4-S-C=N- | 5.0 | 4.1 | 3.5 | 5.7 | 9.4 (2) | 10.5 (2) |
| 28d | 3-NO2 | 3,4-S-C=N- | 7.3 | 11.5 | 5.7 | 16.3 | 33.8 (3) | 37.7 (5) |
| 29b | 3-NH2 | 4-OCH3 | 4.0 | 8.5 | 3.0 | 9.4 | 19.0 (5) | 36.4 (9) |
| 29c | 3-NH2 | 3,4-OCH2O- | 7.1 | 6.1 | 2.8 | 12.3 | 27.9 (4) | 35.4 (5) |
| 29d | 3-NH2 | 3,4-S-C=N- | 1.7 | 2.6 | 1.3 | 2.5 | 11.9 (7) | 14.6 (9) |
| 30c | 3-NHAc | 3,4-OCH2O- | 10.9 | 9.0 | 6.3 | 21.1 | 41.9 (4) | 46.9 (4) |
| 30d | 3-NHAc | 3,4-S-C=N- | 5.8 | 10.1 | 7.7 | 9.5 | 25.4 (4) | 29.5 (5) |
| 31d | 3-NHCO2CH3 | 3,4-S-C=N- | 1.2 | 2.4 | 1.6 | 3.0 | 10.8 (9) | 13.0 (11) |
| LPV | 1.4 | 1.6 | 1.0 | 1.6 | 34.1 (24) | 39.7 (28) | ||
| DRV | 0.4 | 0.6 | 0.4 | 0.4 | 0.5 (1) | 1.0 (2) | ||
a
Antiviral assays were carried out by Monogram Biosciences. WT, wild-type HIV-1 control; WT-A, WT-B, WT-C, patient derived strains of wild-type HIV-1 from clades A, B, and C, respectively; MDR1, drug-resistant HIV-1 variant with protease mutations M46I, I54V, V82A and L90M; MDR, drugresistant HIV-1 control MDRC4; values in the parentheses represent change in EC50 values compared to the WT control.