Table 1.

In vitro Activity of 4a-l^a

Compound	R	Ratio (5/50)b	Fold-Signalc	EC50 hPPARα (μM)d	EC50 hPPARγ (μM)	EC50 hPPARδ (μM)	SIe
4a (A91)	4-OMe	0.5	1.4	4.43±0.01	>100	>100	>20
4b	4-F	0.8	1.3	0.77±0.03	>100	>100	>125
4b*	4-F	0.3	0.4
4c	4-Cl	0.6	1.5	0.83±0.04
4d	4-Br	0.8	1.3	0.97±0.14
4e	4-I	0.7	1.1	1.45±0.02
4f	4-CF3	0.9	0.9	0.96±0.11
4g	4-CN	0.6	1.0
4h	2-F	0.8	1.0
4i	3-F	0.9	1.2	1.18±0.05
4j	2,4-difluoro	1.2	1.2	0.54±0.09	>100	>100	>175
4k	3,4-difluoro	1.1	1.2	0.36±0.01
4l	3,5-difluoro	1.1	1.1
GW590735		1.0	1.0	0.015±0.002
Rosiglitazone					0.28±0.3
GW0742						0.0019±0.002

^aAll analogues contain the carboxylate head-group at the meta-position of the A-ring unless otherwise indicated.

^*indicates a para-carboxylate.

^bRatio of relative light unit (RLU) signal at 5 μM and 50 μM compound concentrations.

^cRatio of maximal signal strength observed for the compound of interest to that obtained with GW590735.

^dEC₅₀ values represent the mean ± SEM of atleast two separate experiments performed in triplicate.

^eSI = EC₅₀ (PPARγ or PPARδ) / EC₅₀ (PPARα). Blank cells indicate compound was not selected for testing in the corresponding assay.