Table 5. Amide Modifications.
| compd no. | stereochem | X | R | T. b. brucei EC50 (μM)a | MRC-5 EC50 (μM)a | mouse microsomal intrinsic clearance (mL min–1 g–1) |
|---|---|---|---|---|---|---|
| 1 | R/S | Cl | MeNH– | 0.03 | >50 | 4.4 |
| 48 | R/S | Cl | Me2N– | 5.4 | >50 | ND |
| 49 | R/S | Cl | EtNH– | 0.09 | >50 | 6.2 |
| 50 | R/S | Cl | n-BuNH– | 19 | >50 | 27 |
| 51 | R/S | Cl | cyclopropyl-NH– | 0.41 | >50 | 5.5 |
| 52 | R/S | Cl | CF3CH2NH– | 1.5 | >50 | 9.0 |
| 53 | R | F | d3-MeNH– | 0.04 | >50 | 1.9 |
a
EC50 values are shown as mean values of two or more determinations. Standard deviation is typically within 2–3-fold from the EC50. ND = not determined.