Table 8. Metabolic Stability and Solubility.

compound	DYRK1A pIC50a	HLM (μL/(min mg))	RLM (μL/(min mg))	solubility (mg/mL)
6b	6.73	449.8b	340.3b	0.05
8b	7.10	75 ± 5	783.7 ± 31	0.01
11	7.12	242 ± 32	231 ± 31	0.10
12	6.94	71 ± 2	434 ± 58	0.06
22	7.10	126 ± 9	119 ± 6	0.06
24	6.96	328 ± 25	929 ± 116	0.01
28	6.94	378 ± 66	448 ± 20	0.02
29	6.83	389 ± 23	184 ± 18	0.05
31	7.18	296 ± 14	130 ± 17	0.04
33	6.87	199b	48 ± 23	1.92
34	7.14	40b	66 ± 24	4.37
63	6.94	160 ± 66	164b	0.01
66	6.86	89 ± 11	77 ± 17	0.07
70	6.80	154 ± 6	96 ± 25	0.47
78	6.87	153.9 ± 39	234.2 ± 17	0.00
95	7.24	697 ± 50	983 ± 39	0.03
109	6.74	93.6 ± 1	105.3 ± 7.0	0.05

^apIC₅₀ in TR-FRET-based ligand-binding displacement assay measured with two technical replicates (n = 1 biological replicate). HLM and RLM determinations mean of n = 2 ± standard deviation (unless otherwise stated).

^bData derived from single experiment. HLM = human liver microsomes, RLM = rat liver microsomes; thermodynamic solubility data was derived from a single experiment at pH 6.8.