TABLE 4
N-[1,3-Di(benzodioxolan-5-yl)propan-2-yl]-N-phenylurea derivatives that induced Ca2+ mobilization in human neutrophils and FPR-transfected HL-60 cells
The EC50 values are presented as the mean ± S.D. of three independent experiments, in which median effective concentration values (EC50) were determined by nonlinear regression analysis of the dose-response curves (five to six points) generated using GraphPad Prism 5 with 95% confidence interval (P < 0.05). Efficacy is expressed as percentage of the response induced by 5 nM fMLF (FPR1) or 5 nM WKYMVm (FPR2 and FPR3).
| Compound | R | Ca2+ Mobilization, EC50, and Efficacy | |||
|---|---|---|---|---|---|
| Neutrophils | FPR1 | FPR2 | FPR3 | ||
| μM (%) | |||||
| AG-10/14 | H | 5.9 ± 1.4 (85) | N.A. | 0.006 ± 0.002 (95) | 3.3 ± 0.7 (45) |
| AG-10/15 | F | 0.7 ± 0.2 (120) | 1.7 ± 0.3 (90) | 0.004 ± 0.001 (100) | 0.7 ± 0.2 (35) |
| AG-10/16 | Cl | 0.06 ± 0.02 (150) | 3.7 ± 0.8 (110) | 0.002 ± 0.0006 (100) | 0.2 ± 0.05 (90) |
| AG-10/17 | Br | 0.1 ± 0.03 (130) | 2.7 ± 0.5 (95) | 0.004 ± 0.001 (105) | 1.7 ± 0.4 (90) |
| AG-10/18 | CH3 | 4.5 ± 1.2 (45) | 5.1 ± 1.8 (50) | 0.07 ± 0.02 (95) | 10.8 ± 3.3 (40) |
N.A., nonactive compound (cell activation was <30% of control level over a concentration range of 0–40 μM).
*Location of the chiral center.