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. 2018 Oct 15;28(19):3255–3259. doi: 10.1016/j.bmcl.2018.07.044

Table 2.

Effect of R1 substitution on kinetic aqueous solubility and human plasma stability.

graphic file with name fx2.jpg

Compound n R1 Kinetic solubility (µM)a CHI logDb H Plasma Stability (half-life min)c
Ponesimod – – 110 3.1 >180
12a 0 NHCH2CONMe2 219 1.9 >180
12b 0 OCH2CH2CH2OH 183 2.3 >180
12c 0 OCH2CH(±CH2OH)OH >250 1.8 >180
15a 1 OMe 155 3.2 >180
15b 2 OMe 79 3.5 >180
a

The aqueous solubility of the test compounds was measured using laser nephelometry.

b

Reverse-phase HPLC method to determine the chromatographic hydrophobicity index (CHI).

c

Incubated in human plasma at 37 °C.