Table 2. Binding Affinities of Compounds 6, 27–42 on Human CCR1 and Human CCR2.
| pKi ± SEM (Ki, nM)a or
displacement at 1 μM (%)b |
|||
|---|---|---|---|
| compd | R2 | CCR1 | CCR2 |
| 27 | H | 42% (41, 42) | 45% (44, 45) |
| 6 | 4-Me | 7.26 ± 0.04 (56) | 7.10 ± 0.03 (81) |
| 28 | 4-Et | 6.78 ± 0.02 (168) | 7.19 ± 0.05 (66) |
| 29 | 4-OMe | 6.60 ± 0.07 (260) | 6.67 ± 0.05 (217) |
| 30 | 4-Cl | 7.41 ± 0.05 (40) | 7.73 ± 0.08 (19) |
| 31 | 4-Br | 7.62 ± 0.05 (24) | 7.80 ± 0.12 (17) |
| 32 | 4-CF3 | 6.86 ± 0.08 (144) | 7.04 ± 0.02 (92) |
| 33 | 3-Me | 6.31 ± 0.07 (500) | 6.58 ± 0.05 (265) |
| 34 | 3-F | 44% (45, 42) | 47% (48, 47) |
| 35 | 3-Cl | 6.28 ± 0.08 (541) | 6.62 ± 0.02 (239) |
| 36 | 3-CF3 | 25% (23, 27) | 6.54 ± 0.11 (305) |
| 37 | 2-F, 4-Me | 7.56 ± 0.10 (29) | 7.44 ± 0.05 (37) |
| 38 (CCR2-RA) | 2-F, 4-Cl | 7.82 ± 0.06 (15) | 8.00 ± 0.09 (11) |
| 39 | 2-F, 4-Br | 7.98 ± 0.04 (11) | 8.25 ± 0.02 (6) |
| 40 | 3,4-diMe | 7.37 ± 0.03 (43) | 7.75 ± 0.02 (18) |
| 41 | 3-Me, 4-Cl | 7.51 ± 0.01 (31) | 8.09 ± 0.08 (9) |
| 42 | 3-F, 4-Me | 7.32 ± 0.07 (49) | 7.24 ± 0.02 (57) |
a
pKi and Ki (nM) values obtained from [3H]-CCR2-RA-[R] binding assays on U2OS membranes stably expressing human CCR1 or human CCR2. Values are means ± standard error of the mean (SEM) of at least three independent experiments performed in duplicate.
b
Percent of [3H]-CCR2-RA-[R] displacement by 1 μM compound. Values represent the mean of two independent experiments performed in duplicate.