Table 2 Initial hit compounds that demonstrate selective TLR inhibition.

IC50 and EC50 values were obtained using RAW264.7 cells. n.d., not done. Values are presented as means ± SD of three independent experiments.


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EntryCompoundR1R2BSCIC50 (μM)
TLR9
TLR7TLR2TLR4EC50 (μM)
toxicity
1TSI-13-50p-OHH1-piperidinyl6.82 ± 0.6515.6 ± 1.08.11 ± 2.1915.8 ± 3.121.4 ± 5.2
2TSI-13-60Hp-OH1-piperidinyl3.04 ± 1.372.07 ± 0.625.9 ± 1.975.56 ± 0.6433.8 ± 2.6
3TSI-13-57p-OHp-OH1-piperidinyl2.7 ± 0.396.03 ± 1.417.37 ± 3.886.38 ± 0.6632.6 ± 3.2
4TSI-13-58p-OHm-OH1-piperidinyl30.2 ± 0.1n.d.50n.d.50
5TSI-13-48p-NO2p-OCH31-piperidinyl3.02 ± 0.1130.0 ± 0.926.4 ± 1.628.6 ± 0.330.6 ± 3.1
6TSI-14-44p-OCH33,4,5-(OCH3)31-piperidinyl3.43 ± 0.492.24 ± 0.632.28 ± 1.101.15 ± 0.3914.6 ± 0.1
7TSI-15-17H5-OCH3-3,4-dioxymethylene1-piperidinyl6.59 ± 0.290.66 ± 0.09505050
8TSI-15-16p-OCH3p-OCH31-pyrazolyl500.85 ± 0.95505050