Table 1 Analogues of compounds 3 and 5 tested by ligand-observed and protein-observed NMR.

No	Solubility (μM)	T2 relaxation-edited	waterlogsy	¹⁵N NMR
compound 5 and analogues
5	410	33.5% reduction, competitive	negative NOE	substantial CSPs
8	140	25.4% reduction, competitive	negative NOE	substantial CSPs
9	650	42.4% reduction, competitive	one peak has negative NOE	substantial CSPs
10	630	0% reduction	negative NOE even for compound alone	no CSPs
11	n.d.	0% reduction	no NOE	n.d.
12	< 50	Not soluble	n.d.	n.d.
13	410	0% reduction	negative NOE even for compound alone	n.d.
14	635	0% reduction	no NOE	n.d.
15	470	20% reduction	negative NOE even for compound alone	no CSPs
compound 3 and analogues
3	220	52.6% reduction	negative NOE	substantial CSPs
16	930	25% reduction	no NOE	n.d.
17	n.d.	0% reduction	no NOE	n.d.
18	900	16% reduction	no NOE	n.d.
19	255	0% reduction	no NOE	n.d.
20	n.d.	0% reduction	no NOE	n.d.
21	n.d.	0% reduction	no NOE	n.d.
22	n.d.	0% reduction	no NOE	n.d.

Compounds 17, 18 and 20–22 were already present in the fragment library and were therefore not re-tested. The original screening hits (3 and 5) are shown as references. “n.d.”, not determined.

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