Table 1.

Apparent IC₅₀ values of the diaryl sulfones and N,N-diarylamine scaffolds for competing with 8-NBD-cAMP in binding EPAC2.

Entry	R1	R2	X	IC50 (µM)	Relative Potency (RA)*
cAMP				40	1
1	4-methyl	2’,4’,6’-trimethyl	SO2	0.5	80
2	4-NH2	2’-SO3H-4’-NH2	NH	18	2.2
5a	2,4,5-trimethyl	2’,4’,6’-trimethyl	SO2	0.7	57.1
5b	4-pentyl	2’,4’,6’-trimethyl	SO2	>300	<0.13
5c	4-cyclohexyl	2’,4’,6’-trimethyl	SO2	>300	<0.13
8a	4-iodo	2’,4’,6’-trimethyl	SO2	4	10
8b	4-methoxy	2’,4’,6’-trimethyl	SO2	1.9	21.1
9	4-(2-fluoro-5-pyridinyl)	2’,4’,6’-trimethyl	SO2	>300	<0.13
10	4-hydroxyl	2’,4’,6’-trimethyl	SO2	13.5	3.0
11a	4-O-cyclohexyl	2’,4’,6’-trimethyl	SO2	>300	<0.13
11b	4-O-piperidinyl-1-Boc	2’,4’,6’-trimethyl	SO2	>300	<0.13
11c	4-O-piperidinyl	2’,4’,6’-trimethyl	SO2	>300	<0.13
11d	4-O-2-ethylamino	2’,4’,6’-trimethyl	SO2	>300	<0.13
14a	4-methyl	2’,4’,6’-trimethyl	NH	3.8	10.5
14b	3,5-dichloro	2’,4’,6’-trimethyl	NH	0.9	44.4
14c	2,5-dichloro	2’,4’,6’-trimethyl	NH	0.4	100
17			NH	>300	<0.13

^*RA = IC_{50, cAMP}/ IC_{50, compound}