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. 2014 Jan 22;5(4):309–314. doi: 10.1021/ml400379x

Table 1. Enzymatic and Cellular Activity and Pharmaceutical Properties of Coumarin Derivatives.

graphic file with name ml-2013-00379x_0006.jpg

              IC50 (nM)
        
compd R2 X1 X2 X3 X4 X5 HCT116 HT-29 C-Raf MEK1 solubility (μg/mL) CLint human (μL/min/mg) PAMPA (10–6 cm/s) AUC poa (μM·h)
11a H CH CH CH CH CH 24 9 300 110 32 20 6 78b
11b H N CH CH CH CH 1100 600 2500 440 43 3 3 ND
11c H CH N CH CH CH 270 73 70 110 320 7 6 314
11d H CH CH N CH CH 32 25 32 99 55 6 7 134
11e H CH CH CH N CH >10000 >10000 >50000 >50000 240 ND ND ND
12a Me CH CH CH CH CH 22 8 78 29 11 17 4 18
12f Me CH CH CH CH N >10000 5700 27000 37000 425 ND ND ND
a

Compounds were evaluated in 24 h exposure studies in mice at 100 mg/kg and formulated as solutions of 5% DMSO, 5% Cremophor EL, 15% PEG400, 15% HPCD, and 60% water.

b

Sodium salt was used.