Table 4.

SAR and apparent cell permeability data for CK1δ/ε inhibitors with bioisosters or heterocyclic replacements of the benzimidazole unit (R₅)

№	R5	CK1δ IC50 (nM)[a]	CK1ε IC50 (nM)[a]	MDA-MB-231EC50 (nM)[b]	PAMPA[c] Papp·10−6
13		44	260	26	0.4
50		42	150	> 10000	< 0.1
51		9	115	> 10000	< 0.1
52		215	280	1400	< 0.1
53		> 10000	> 10000	- [d]	< 0.1
54		> 10000	> 10000	- [d]	< 0.1
55		245	380	1850	0.3
56		50	54	7160	7.1
57		180	205	> 10000	0.1
58		85	- [d]	> 10000	6.8
59		98	- [d]	> 10000	- [d]
60		80	- [d]	6460	- [d]
61		37	- [d]	> 10000	- [d]
62		89	- [d]	> 10000	< 0.1

^[a]Biochemical assay.

^[b]Cellular proliferation assay.

^[c]Permeability, Parallel Artificial Membrane Permeability Assay (PAMPA), see experimental section for details

^[d]Not determined