Table 3. N-Aryl Methylcyclohexane TRPV4 Potency SAR.

cmpd	R	hTRPV4 IC50 ± SEM (nM)a	ChromLogDb	LLE	Me effectc
14	p-F	96 ± 17	4.9	2.1	20×
15	H	49 ± 5.9	5.0	2.3	17×
16	p-OEt	5.2 ± 0.3	5.4	2.9	26×
17	m-OEt	1.6 ± 0.2	5.3	3.5	45×
18	m-Cl	48 ± 7.5	5.7	1.6	5×
19	o-Cl	2.5 ± 0.3	4.8	3.8	25×
20	o-F	5.2 ± 1.0	4.9	3.4	100×
21	o-Me	1.7 ± 0.2	4.8	4.0	200×
22	o-OMe	1.2 ± 0.2	4.6	4.3	280×

^aTRPV4 IC₅₀ is an average of at least two measurements.

^bLLE = TRPV4 pIC₅₀ – ChromLogD.

^cMethyl effect is the fold change in hTRPV4 IC₅₀ for the corresponding analogs in Table 2.