Table 2. Inhibition of NOTUM activity. SAR of the amide heterocycles.

#	R	IC50 a (μM)	#	R	IC50 a (μM)
3		33	21		1.6
22		9.4	23		3.6
24		72	25		100
26		0.21	27		0.68
28		0.33	29		0.24
30		0.52	31		0.98
32		0.36	33		0.27
34		0.27	35		0.28
36		0.20	37		0.068
38		0.032	39		0.12
40		0.44	41		0.27
42		7.4	43		2.5
44		1.2	45		0.085
46		0.97	47		0.43
48		15	49		0.67
50	—	0.069	51	—	19
52	—	5.2	53	—	5.7
54	—	7.9

^aValues are geometric means of n = 2–8 experiments quoted to 2 s.f. Screening data only passed the quality control criteria if the screening plates demonstrated a Z′ > 0.5 and the NOTUM inhibition activity of the positive control was within acceptable limits (IC₅₀ 0.6–1.1 nM). Differences of <2-fold should not be considered significant. See also ESI Table S1 for s.e.m.