Table 1.
Anti- DENV and BCR-Abl activity of a focused library of 2,4-disubstituted pyrimidine analogs and compound 3a.
| Core structure | Compound | R3 | IC90 (μM) | BHK21-DENV2 CC90 (μM) | Bcr-Abl Ba/F3 IC50 (μM) | |||
|---|---|---|---|---|---|---|---|---|
| DENV1 | DENV2 | DENV3 | DENV4 | |||||
|
8b |
|
4 | 5 | 10 | 40 | 60 | >10 |
| 11a |
|
10 | 17.5 | >40 | 10 | 100 | >10 | |
| 11b |
|
20 | 25 | 40 | >40 | 40 | >10 | |
| 11c |
|
10 | 25 | >40 | 5 | 80 | >10 | |
| 11d |
|
4 | 20 | 30 | >40 | 50 | >10 | |
| 11e |
|
10 | 10 | >40 | 20 | 100 | >10 | |
| 11f |
|
20 | 25 | >40 | 10 | 80 | >10 | |
| 11g |
|
10 | 25 | >40 | >40 | 100 | >10 | |
| 11h |
|
20 | 25 | 5 | 40 | 50 | >10 | |
| 11i |
|
5 | 10 | >40 | 40 | 100 | >10 | |
| 11j |
|
40 | 15 | >40 | 40 | >100 | >10 | |
|
8c |
|
1 | 5 | 40 | 17.5 | 100 | >10 |
| 12a |
|
1 | 20 | >40 | 10 | 90 | >10 | |
| 12b |
|
1 | 25 | >40 | 15 | 90 | >10 | |
| 12c |
|
3 | 5 | >40 | 10 | 90 | >10 | |
| 12d |
|
3 | 7.5 | 40 | 7.5 | 75 | >10 | |
| 12e |
|
4 | 25 | >40 | 15 | 50 | >10 | |
| 12f |
|
7 | 17.5 | >40 | 35 | >100 | >10 | |
|
3a | 20 | 7.5 | >40 | 15 | 40 | >10 | |
Columns are: 1. core chemical structure; 2. compound code; 3. chemical structure of R3 group; 4. IC90 values against DENV1-4 viruses in the infectivity assay outlined in Figure 2; 5. CC90 in micromolar for viability of BHK21 cells; 6. IC50 in micromolar for viability of BCR-Abl-dependent murine Ba/F3 cells.