Table 2.
SAR exploration of the pyridine moiety.
 | ||||||||
| Compd. | Ar | SMS2 |
SMS1 |
Selectivity ratio | ClogPb | LLEc | ||
| Inhibition @ 1 μmol/L (%)a | IC50 (nmol/L)a | Inhibition @ 100 μmol/L (%)a | IC50 (μmol/L)a | |||||
| 5a |  |
66 | 400 | 20 | 219 | 547 | 3.07 | 3.33 |
| 7a |  |
41 | 1793 | 53 | – | – | 3.44 | 2.31 |
| 7b |  |
7 | – | −39 | – | – | 3.60 | – |
| 7c |  |
56 | – | 52 | – | – | 3.43 | – |
| 7d |  |
12 | – | 57 | – | – | 3.43 | – |
| 7e |  |
3 | – | −20 | – | – | 3.45 | – |
| 7f |  |
−4 | – | −17 | – | – | 3.40 | – |
| 7g |  |
12 | – | 28 | – | – | 3.47 | – |
| 7h |  |
−3 | – | 22 | – | – | 3.46 | – |
| 7i |  |
25 | – | 22 | – | – | 2.69 | – |
| 7j |  |
−16 | – | 5 | – | – | 2.55 | – |
| 7k |  |
3 | – | 60 | – | – | 3.79 | – |
a
SMS activity is measured by purified SMS enzyme inhibitory assay in vitro. The results are expressed as the mean of duplicates. Selectivity ratio is calculated by a formula of “IC50, SMS1/IC50, SMS2”.
b
ClogP is predicted by SwissADME.
c
LLE is calculated by a formula of “pIC50, SMS2 – ClogP”. —, not applicable.