Table 1. SAR and PK Properties of GSNOR Inhibitors.
compd | R1 | R2 | R3 | GSNOR IC50 (nM) | % F | CL (mL/min/kg) |
---|---|---|---|---|---|---|
5a | H | H | H | 570 | 86.5 | 8.9 |
5b | H | H | Me | 360 | 46.8 | 11.8 |
5c | OMe | H | H | 460 | ||
5d | OMe | H | F | 240 | ||
5e | OMe | H | Cl | 190 | ||
14 | OMe | H | CF3 | 450 | ||
5f | OMe | H | Me | 210 | 16.2 | 35.4 |
13a | F | H | Me | 500 | ||
13b | Cl | H | Me | 120 | 20.7 | 16.0 |
13c | Br | H | Me | 160 | 18.0 | 21.4 |
5g | CN | H | Me | 563 | 16.3 | 25.5 |
5h | OH | H | Me | 160 | ||
13d | CF3 | H | Me | 3990 | ||
15 | CONH2 | H | Me | 3920 | ||
N6022 | 1H-imidazol-1-yl | H | Me | 20 | 4.4 | 37.8 |
16 | Cl | MeO | Me | 56 | 22.4 | 20.2 |
13e | MeO | Cl | Me | 200 | ||
17 | Br | MeO | Me | 96 | 21.8 | 22.4 |
5j | Cl | OH | Me | 55 | 2.72 | 33.4 |
13f | Cl | CONH2 | Me | 160 | ||
18 | Cl | EtO | Me | 170 | ||
19 | Cl | PrO | Me | 110 | ||
20 | Cl | NMe2 | Me | 350 | ||
21 | Cl | NHCHO | Me | 580 | ||
13g | Cl | Cl | Me | 160 | ||
13h | Cl | F | Me | 120 | ||
13i | Cl | CF3 | Me | 330 |