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

Table 3.

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

Compound	R¹	H Plasma Stability (half-life min)^a	Kinetic solubility (µM)^b	CHI logD^c	H Skin S9 (half-life min)^d	S1PR1 pIC₅₀^e
11	OH	>180	–	–	–	<6 (0)
12d		180	117	3.0	152	–
12e		61	79	2.8	40	–
12f		9	79	3.3	23	<6 (0)

Incubated in human plasma at 37 °C.

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

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

Stability measured in skin S9 over 180 mins in the presence of enzymatic cofactors.

All pIC₅₀s reported in this table correspond to n of 2, reported as their geometric mean. The range of pIC₅₀ values is provided in brackets.