[Design and synthesis of peroxisome proliferator-activated receptor (PPAR) delta agonists and its implication to the driving force to elicit PPAR delta selectivity].

A series of 3-(4-alkoxypheny)propanoic acid derivatives was prepared as candidate peroxisome proliferator-activated receptor (PPAR) delta-selective agonists, based on our previously discovered potent human PPARalpha/delta dual agonist TIPP-401 as a lead compound. Structure-activity relationship studies clearly indicated the importance of the chain length of the alkoxy group at the 4-position, and the n-butoxy compound exhibited the most potent PPARdelta transactivation activity and highest PPARdelta selectivity. The (S)-enantiomer of a representative compound (TIPP-204) exhibited extremely potent PPARdelta transactivation activity, comparable to that of the known PPARdelta-selective agonist GW-501516.

Gamma-carboline derivatives with anti-bovine viral diarrhea virus (BVDV) activity.

Based on anti-viral screening of our heteroaromatics derived from thalidomide, the gamma-carboline skeleton has been identified as a superior scaffold structure for compounds with potent anti-bovine viral diarrhea virus (BVDV) activity. Structural development studies led to a potent anti-viral agent, SK5M (5-methyl-gamma-carboline), with the EC(50) of 0.26 microM.

Design, synthesis, and evaluation of potent, structurally novel peroxisome proliferator-activated receptor (PPAR) delta-selective agonists.

A series of 3-(4-alkoxyphenyl)propanoic acid derivatives was prepared as candidate peroxisome proliferator-activated receptor (PPAR) delta-selective agonists, based on our previously discovered potent human PPARalpha/delta dual agonist TIPP-401 as a lead compound. Structure-activity relationship studies clearly indicated the importance of the chain length of the alkoxy group at the 4-position, and the n-butoxy compound exhibited the most potent PPARdelta transactivation activity and highest PPARdelta selectivity. The (S)-enantiomer of a representative compound exhibited extremely potent PPARdelta transactivation activity, comparable with or somewhat superior to that of the known PPARdelta-selective agonist, GW-501516.