Table 5.
Activity of compounds 6a–w (Scheme 1) in HL-60 cells expressing human FPR1, FPR2,or FPR3
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|---|---|---|---|---|---|---|---|
| Compd. | R | OCH3 | R1 | Ca2+ Mobilization EC50 (µM) and Efficacy (%) a | |||
| FPR1 | FPR2 | FPR3 | W.T.b | ||||
| A16 | CH3 | m | 3,4-methylenedioxy | 2.3 (50) | N.A. | N.A. | N.A. |
| B16 | CH3 | p | Br (p) | N.A. | 2.4 | N.A. | N.A. |
| C16 | CH3 | m | I (p) | 2.8 (90) | 6.8 (40) | 13.0 (30) | N.A. |
| D16 | CH3 | m | Br (p) | 3.4 (75) | 3.8 (70) | N.A. | N.A. |
| 6a | H | m | Br (p) | 6.1 (125) | 7.7 (60) | 14.6 (25) | N.A. |
| 6b | CH2CH3 | m | I (p) | 4.2 (70) | 5.5 (65) | N.A. | N.A. |
| 6c | CH(CH3)2 | m | Br (p) | 4.5 (135) | 7.2 (90) | 17.4 (30) | N.A. |
| 6d | C6H11 | m | Br (p) | 10.8 (80) | N.A. | N.A. | N.A. |
| 6e | C6H5 | m | Br (p) | 9.0 (110) | 4.3 (25) | N.A. | N.A. |
| 6f | C6H5 | m | 3,4-methylenedioxy | N.A. | N.A. | N.A. | N.A. |
| 6g | C6H5 | m | F (p) | N.A. | N.A. | N.A. | N.A. |
| 6h | 2-thienyl | p | Br (p) | N.A. | N.A. | N.A. | N.A. |
| 6i | 2-thienyl | m | 3,4-methylenedioxy | N.A. | N.A. | N.A. | N.A. |
| 6j | 2-thienyl | m | F (p) | N.A. | N.A. | N.A. | N.A. |
| 6k | C6H4-OCH3 (p) | p | Br (p) | N.A. | N.A. | N.A. | N.A. |
| 6l | C6H4-OCH3 (p) | m | 3,4-methylenedioxy | N.A. | N.A. | N.A. | N.A. |
| 6m | C6H4-OCH3 (p) | m | F (p) | N.A. | N.A. | N.A. | N.A. |
| 6n | C6H4-Cl (p) | p | Br (p) | N.A. | N.A. | N.A. | N.A. |
| 6o | C6H4-Cl (p) | m | 3,4-methylenedioxy | N.A. | N.A. | N.A. | N.A. |
| 6p | C6H4-Cl (p) | m | F (p) | N.A. | N.A. | N.A. | N.A. |
| 6q | C6H4-CH3 (p) | p | Br (p) | N.A. | N.A. | N.A. | N.A. |
| 6r | C6H4-CH3 (p) | m | 3,4-methylenedioxy | N.A. | N.A. | N.A. | N.A. |
| 6s | C6H4-CH3 (p) | m | F (p) | N.A. | N.A. | N.A. | N.A. |
| 6t | C6H4-F (p) | p | Br (p) | N.A. | N.A. | N.A. | N.A. |
| 6u | C6H4-F (p) | m | 3,4-methylenedioxy | N.A. | N.A. | N.A. | N.A. |
| 6v | C6H4-F (p) | m | F (p) | N.A. | N.A. | N.A. | N.A. |
| 6w | CH2-C6H5 | p | Br (p) | N.A. | N.A. | N.A. | N.A. |
N.A., no activity (no response was observed during first 2 min after addition of compounds under investigation) considering the limits of efficacy > 20 % and EC50 < 50 µM.
W.T., wild-type nontransfected HL-60 cells. The EC50 values are presented as the average mean of three independent experiments, in which EC50 values were determined by nonlinear regression analysis of the dose-response curves (5–6 points) generated using GraphPad Prism 5 with 95% confidential interval (p< 0.05). Efficacy (in brackets) is expressed as % of the response induced by 5 nM fMLF (FPR1) or 5 nM WKYMVm (FPR2 and FPR3).
