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. 2019 Nov 19;62(24):11035–11053. doi: 10.1021/acs.jmedchem.9b00742

Table 2. Characterization of Compounds 2436 in hCCR2 and hCCR5a.

graphic file with name jm9b00742_0007.jpg

    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
a

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.

b

pKi values from the displacement of ∼6 nM [3H]-CCR2-RA-[R] from U2OS cells stably expressing CCR2, at 25 °C.

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.

d

No inhibition was observed at the concentration of 1 μM; instead some CCL3 stimulation was measured.