PPAR Research

Review Article

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 1

SAR 1: effect of the acidic partial structure in the present series of compounds.



		Transactivation activity
		EC₅₀ (nM)^(a)
No.	R	PPAR	PPAR	PPAR

7	COOH	ia^(b)	ia	ia
8	CH₂COOH	ia	ia	ia
9	(CH₂)₂COOH	1300	ia	ia
10	CH₂CH(Me)COOH^(c)	240	2800	ia
11	CH₂CH(Et)COOH^(c)	40	3600	1000
12	CH₂CH(n-Pr)COOH^(c)	360	2400	ia
13	CH₂CH(i-Pr)COOH^(c)	290	ia	ia
14	CH₂CH(n-Bu)COOH^(c)	1000	ia	2500
15	CH₂CH(Ph)COOH^(c)	ia	ia	ia
16	CH₂CH(OMe)COOH^(c)	230	ia	ia
17	CH₂CH(OEt)COOH^(c)	1600	3000	2800
18	CH₂CH(OPh)COOH^(c)	ia	ia	ia
19	CH₂C(Me)₂COOH	2900	ia	ia
20	CH₂C(Et)₂COOH	2800	ia	ia
21	CH₂CH(SEt)COOH^(c)	1600	3000	2800
22	CH₂CH(SPh)COOH^(c)	ia	ia	ia
23	CH₂CH(SBn)COOH^(c)	ia	ia	ia

	KRP-297	1000	ia	800

^(a) Compounds were screened for agonist activity on PPAR-GAL4 chimeric receptors in transiently transfected CHO-K1 cells as described. 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,^(c) assayed as a racemate.