Table 2.
Enzyme and parasite growth inhibition, monolayer permeability, and microsomal stability of C5’-N-alkyl analogs.
| Cmpd | R1 | R2 | AdoMetDC IC50 with PIa |
95% CIb | AdoMetDC IC50 without PIa |
95% CIb | EC50 (T. b. brucei)d |
95% CIb |
Pappe (nm/s) |
S9 h/mf (t1/2, min) |
|---|---|---|---|---|---|---|---|---|---|---|
| 10a | H | Me | >50 µM | NDc | >50 µM | ND | >25 µM | ND | 321/51 | <2.5 |
| 10c | Me | c-Pr | 42 µM | (35–52) | >50 µM | ND | 3.0 µM | (2.5–3.6) | 767/312 | <2.5 |
| 11a | H | Me | 3.0 µM | (2.7–3.3) | 22% at 50 µM | ND | 0.42 µM | (0.33–0.54) | ND | >90 |
| 11b | H | (CH2)2F | >50 µM | ND | >50 µM | ND | >25 µM | ND | 9.3 | >90 |
| 11c | Me | c-Pr | >50 µM | ND | >50 µM | ND | >3 µM | ND | 14 | >90 |
| 11d | Me | (CH2)2OH | >50 µM | ND | >50 µM | ND | >25 µM | ND | 6.8 | >90 |
| 1 | H | Me | 0.041 µM | (0.036–0.047) | 2.4 µM | (1.9–3.1) | 0.010 µM | (0.008–0.012) | 7.1 | >90 |
| 12b | H | (CH2)2F | 36% at 50 µM | ND | >50 µM | ND | >25 µM | ND | <1 | >90 |
| 12c | Me | c-Pr | >50 µM | ND | >50 µM | ND | >3 µM | ND | 10 | >90 |
a, b, c, d, e, f
See footnotes to Table 1.