Table 2. Characterization of Compounds 24–36 in hCCR2 and hCCR5a.
hCCR2 | hCCR5 | ||
---|---|---|---|
compd | R3 | pKi ± SEM (Ki, nM)b | pIC50 ± SEM (IC50, nM) or inhibition at 1 μM (%)c |
8 | cPr | 8.90 ± 0.04 (1.3) | 6.24 ± 0.004 (571) |
24 | Me | 7.78 ± 0.07 (17.2) | –35% |
25 | Et | 8.40 ± 0.07 (4.0) | 29% |
26 | Pr | 8.46 ± 0.07 (3.6) | 64% |
27 | iPr | 8.72 ± 0.05 (1.9) | 6.56 ± 0.05 (281) |
28 | Bu | 8.64 ± 0.03 (2.3) | 6.29 ± 0.05 (519) |
29 | 2-EtBu | 8.20 ± 0.04 (6.4) | 29% |
30 | Pent | 8.14 ± 0.03 (7.2) | 38% |
31 | cPent | 8.81 ± 0.04 (1.6) | 6.43 ± 0.08 (388) |
32 | Hex | 7.66 ± 0.02 (22.0) | –63%d |
33 | Hept | 6.76 ± 0.05 (178.1) | –265%d |
34 | Ph | 7.64 ± 0.17 (26.7) | –41%d |
35 | 4-MePh | 6.81 ± 0.07 (158.8) | –13%d |
36 | CH2CH2Ph | 7.29 ± 0.05 (52.3) | –42%d |
Data are presented as the mean pKi/pIC50 ± standard error of the mean (SEM) and mean Ki/IC50 (nM) of at least three independent experiments performed in duplicate.
pKi values from the displacement of ∼6 nM [3H]-CCR2-RA-[R] from U2OS cells stably expressing CCR2, at 25 °C.
Percent inhibition of β-arrestin recruitment in U2OS cells stably expressing CCR5 by 1 μM compound, in the presence of CCL3 (pEC80 = 7.9). pIC50 values were determined for compounds displaying more than 70% inhibition. % Inhibition values are presented as mean values of at least two independent experiments, performed in duplicate.
No inhibition was observed at the concentration of 1 μM; instead some CCL3 stimulation was measured.