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 5

PPARs transactivation activity of the present series of compounds.

					Transactivation activity
					EC50 (nM)^(a)
No.	R^1	R^2	R^3	stereo	PPAR	PPAR	PPAR
49	H	Me	Et	rac	18	170	2600
50	H	Et	Et	rac	12	15	1800
51	H	n-Pr	Et	rac	77	6.8	1300
52	H	n-Bu	Et	rac	520	4.8	1300
53	H	n-Hexyl	Et	rac	1200	45	2300
54	H	Bn	Et	rac	>10000	110	6200
55	F	Me	Et	rac	8.2	21	2200
56	F	n-Pr	Et	rac	41	1.7	650
57	F	n-BU	Et	rac	280	1.9	1400
58	H	Me	H	rac	210	3000	>10000
59	H	Me	Me	rac	19	210	>10000
60	H	Me	n Pr	rac	70	120	3600
61	H	Me	n BU	rac	230	700	2400
62	F	Me	n Pr	rac	29	40	1500
63	F	Me	n BU	rac	140	220	1000
64	F	n-BU	n Pr	rac	820	5.1	1000
65	F	n-BU	Et	S	250	0.91	1100
66	F	n-BU	Et	R	620	8.2	7600
GW-501516					1000	1.8	8600

^(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.