Table 1.
Structures and enzyme inhibitory activities of the derived APN inhibitors.
| Compound | X | R | Inhibitory rate (%) a | IC50 (µM) a |
|---|---|---|---|---|
| D1 | CH2 | -CF3(p) | 35.0±1.51 | ND |
| D2 | CH2C6H4 | -CF3(p) | 13.3±3.25 | ND |
| D3 | CH2 | -H | 74.4±6.42 | 6.24±0.43 |
| D4 | CH2C6H4 | -H | 19.4±4.53 | ND |
| D5 | CH2 | -CF3(o) | 62.9±8.72 | 14.9±1.03 |
| D6 | CH2C6H4 | -CF3(o) | 15.3±3.66 | ND |
| D7 | CH2C6H4 | -OCH3(o) | 17.9±0.84 | ND |
| D8 | CH2 | -OCH3(p) | 56.7±0.42 | 25.0±3.32 |
| D9 | CH2C6H4 | -OCH3(p) | 24.0±0.25 | ND |
| D10 | CH2 | -F(p) | 42.5±1.42 | ND |
| D11 | CH2C6H4 | -F(p) | 35.0±4.57 | ND |
| D12 | CH2 | -F(m) | 74.9±4.35 | 8.92±0.38 |
| D13 | CH2C6H4 | -F(m) | 13.2±0.40 | ND |
| D14 | CH2 | -F(o) | 74.3±6.16 | 7.74±0.33 |
| D15 | CH2C6H4 | -F(o) | 28.7±2.75 | ND |
| D16 | CH2 | -CH3(o) | 74.5±4.66 | 7.9±0.27 |
| D17 | CH2C6H4 | -CH3(o) | 23.6±4.51 | ND |
| D18 | CH2 | -CH2CH3(p) | 53.2±2.08 | ND |
| D19 | CH2C6H4 | -CH2CH3(p) | 19.5±4.22 | ND |
| D20 | CH2C6H4 | -Cl(o) | 19.1±4.17 | ND |
| D21 | CH2 | -Br(m) | 78.2±5.43 | 7.82±1.05 |
| D22 | CH2C6H4 | -Br(m) | 19.2±3.70 | ND |
| D23 | CH2C6H4 | -2,4-2F | 65.0±5.97 | 49.74±9.29 |
| D24 | CH2 | -3,5-2F | 71.3±4.25 | 7.13±0.13 |
| D25 | CH2C6H4 | -3,5-2F | 27.9±5.85 | ND |
| D26 | CH2 | -( CH2)2CH3(p) | 53.1±7.31 | ND |
| D27 | CH2C6H4 | -( CH2)2CH3(p) | 20.4±5.78 | ND |
| D28 | CH2 | -2,5-2F | 78.0±3.95 | 4.85±0.55 |
| D29 | CH2 | -2-Cl-6-F | 60.0±4.95 | 9.23±0.67 |
| Bestatin | 53.9±0.77 | 18.33±1.68 |
a
Each value is the mean of at least three experiments.
ND, Not determined.