Table 2. In Vitro Activity of Selected Compounds^a.

compound	EC50 hPPARα (μM ± SEM)b	hill slope	maximal relative activation of hPPARβ/δ (% ± SEM)c,e	maximal relative activation of hPPARγ (% ± SEM)d,e	clogPf	ligand efficiencyg
A229 (6l)	0.59 ± 0.051	1.4	12.1 ± 1.0	11.2 ± 3.0	4.8	0.341
3g	0.083 ± 0.011	2.2	31.1 ± 1.0	22.5 ± 6.7	5.4	0.347
6d	0.080 ± 0.032	1.0	25.1 ± 4.1	35.7 ± 4.2	5.7	0.343
6j	0.064 ± 0.018	1.8	6.1 ± 3.6	9.3 ± 2.3	5.7	0.337
8b	0.30 ± 0.096	1.5	21.1 ± 6.2	19.9 ± 10.3	4.6	0.317
GW7647	0.0057 ± 0.00029	1.8	N.D.	N.D.	7.0	0.340

^aEC₅₀ values and maximal relative activation were calculated as mean ± SEM of at least two independent experiments performed in triplicate.

^bFull dose–response curves are shown in the Supporting Information (Figure S9).

^cMaximal relative activation of hPPARβ/δ refers to the activity of known PPARβ/δ agonist GW0742 at 0.0075 μM concentration, which was defined as 100% activation.

^dMaximal relative activation of hPPARγ refers to the activity of known PPARγ agonist rosiglitazone at 2.5 μM concentration, which was defined as 100% activation.

^eFor PPARβ/δ and PPARγ assays, a six-point dose–response range was completed for each compound ranging from 13 nM to 100 μM (13 nM, 77 nM, 463 nM, 3 μM, 17 μM, and 100 μM). Because of observed cytotoxicity at 100 μM for several compounds, the agonism level at 17 μM was selected as the point of comparison. N.D. = not determined.

^fCalculated logP (clogP) values were predicted using ADMETlab 2.0.¹⁹

^gLigand efficiency (LE) values were calculated using the equation: LE = (1.37/the number of heavy atoms) × pEC₅₀.²⁰