Structural Development Studies of Subtype-Selective Ligands for Peroxisome Proliferator-Activated Receptors (PPARs) Based on the 3,4-Disubstituted Phenylpropanoic Acid Scaffold as a Versatile Template

Table 4

In vitro functional PPAR transactivation activity of substituted phenylpropanoic acids.

				Transactivation activity
				EC50 (nM)^(a)
No.	X	Y	stereo	PPAR	PPAR	PPAR
33	4-CF3	H	rac	19	200	2600
38	4-CF3	2-F	rac	10	24	2200
39	4-CF3	3-F	rac	11	51	6000
40	3-F	4-CF3	rac	250	2000	ia^(b)
41	4-CF3	2-F	S	10	12	1900
42	4-CF3	3-F	S	12	23	4900
43	4-CF3	3-F	R	150	840	ia^(b)

^(a) Compounds were screened for agonist activity on PPAR-GAL4 chimeric receptors in transiently transfected HEK-293 cells. The EC₅₀ value is the molar concentration of the test compound that causes 50% of the maximal reporter activity,^(b) “ia” means inactive at the concentration of 10 M.