Table 1. In Vitro Antitrypanosomal Evaluation of N-Benzyl-2-thiohydantoins Derivatives (SAR R1–R2).
compd | R1 | R2 | T.brucei EC50 (nM)a |
---|---|---|---|
1 | 4-OMe | 3-Cl | 346 |
14 | 4-OMe | H | >10000 |
15 | 3-Cl | H | >20000 |
16 | H | H | >10000 |
17 | 3-OMe | H | >10000 |
18 | 4-Cl | H | >10000 |
19 | 2-Cl | H | >20000 |
20 | 5-Cl | 2-OMe | >10000 |
21 | 4-CF3 | 3-Cl | >10000 |
22 | 4-F | 3-Cl | >10000 |
23 | 5-Cl | 2-F | >10000 |
24 | 4-F | H | >10000 |
25 | 3-CF3 | 5-CF3 | >10000 |
26 | 4-N(Me)2 | H | 1500 |
27 | 4-isoPr | H | >10000 |
28 | 4-OH | H | >10000 |
29 | 4–C(O)Me | H | >10000 |
30 | 4-COOH | H | >10000 |
31 | 4-OMe | 2-OMe | 637 |
32 | 4-OMe | 3-OMe | 161 |
33 | 4-OMe, 5-OMe | 3-OMe | >10000 |
34 | 4-N(Me)2 | 3-Cl | 16 |
35 | 4-N(Me)2 | 3-F | 125 |
36 | 4-N(Me)2 | 3-OMe | 13 |
37 | 4-OMe | 3-N(Me)2 | 431 |
Concentration of compound required to inhibit growth by 50% (EC50) in T. bruceibrucei strain BF427. Pentamidine isethionate was included as a control for all of the T. brucei EC50 assays with average ± SEM: 1.15 ± 0.09 nM (n = 32).