Table 3. Pendant Ether Modifications.
| microsomal intrinsic clearanceb (mL min–1 g–1) |
|||||||
|---|---|---|---|---|---|---|---|
| compd no. | stereochem | R | T. b. brucei EC50 (μM)a | MRC-5 EC50 (μM)a | m | r | h |
| 1 | R/S | 4-chlorophenyl | 0.03 | >50 | 4.4 | 4.4 | 2.6 |
| 28 | R/S | benzyl | 1.9 | >50 | ND | ND | ND |
| 29 | R/S | 4-chloro-3-fluorophenyl | 0.03 | >50 | 4.4 | 13.5 | 3.3 |
| 30 | R/S | 3,4-dichlorophenyl | 0.40 | >50 | 9.1 | ND | ND |
| 31 | R/S | phenyl | 0.04 | >50 | 6.9 | 9.0 | 1.4 |
| 32 | R/S | 3-tetrahydropyran | 1.1 | >50 | 1.2 | ND | ND |
| 33 | R | 4-methyl-3-pyridyl | 0.39 | >50 | ND | ND | ND |
| 34 | R/S | 4-methylphenyl | 0.03 | >50 | 6.5 | 47 | 2.4 |
| 35 | R/S | 4-fluorophenyl | 0.02 | >50 | 1.2 | ND | ND |
| 36 | R | 4-fluorophenyl | 0.04 | >50 | 1.2 | 4.9 | 1.3 |
| 37 | R | 3,4-difluorophenyl | 0.03 | >50 | 3.2 | ND | ND |
| 38 | R | phenyl-d5 | 0.05 | >50 | ND | ND | ND |
a
EC50 values are shown as mean values of two or more determinations. Standard deviation is typically within 2–3-fold from the EC50.
b
m/r/h = mouse/rat/human; ND = not determined.