Table 1.
Primary Screen Hit Confirmation
| Chemotype | Structure | MIC90(µM) | Enzyme IC50(nM) | ||
|---|---|---|---|---|---|
| Hit | wt | DHFR-oe | Mtb | Human | |
| A. WR99210(WR) | |||||
| WR99210 |  |
1–2 | 15–30 | 14a | 9.0 |
| WR-1 |  |
0.3 | 2.0 | 10.1 | 8.7 |
| WR-2 |  |
0.5 | 2.0 | 5.6 | 3.6 |
| WR-3 |  |
1.0 | 15.6 | nd | nd |
| WR-4 |  |
1.0 | 11.7 | nd | nd |
| WR-5 |  |
0.5 | 15.6 | nd | nd |
| WR-6 |  |
0.7 | 11.7 | nd | nd |
| WR-7 |  |
0.5 | >2 | nd | nd |
| WR-8 |  |
0.5 | 2.0 | nd | nd |
| WR-9 |  |
0.5 | >2 | nd | nd |
| WR-10 |  |
2.0 | 23.4 | nd | nd |
| B. Pyrido diamine Pyrimidine (PDP) | |||||
| PDP-1 |  |
1.3 | 30.0 | 8.2 | 6.7 |
| C. Pyrroloquinazolinediamine (PQD | |||||
| PQD-1 |  |
0.5 | >2 | 10.1 | 6.8 |
| PQD-2 |  |
1.0 | 15.6 | nd | nd |
| D. Diaminopteridine (Dpt) | |||||
| Dpt-1 |  |
2.9 | 250.0 | 54.5 | 382.1 |
| Dpt-2 |  |
15.6 | >250 | 70.5 | 3844.4 |
| E. Diaminoquinazoline (DQn) | |||||
| DQn-1 |  |
0.03 | 1.0 | 8.7 | 7.6 |
| Trimetrexatea,b |  |
6.3 | >100 | 17.0 | nd |
a
Data from Nixon et al.15
b
The compound was not identified in the screen.