M. Nomura, T. Tanase, T. Ide
Jul 10, 2003
Citations
0
Influential Citations
63
Citations
Journal
Journal of Medicinal Chemistry
Abstract
Substituted phenylpropanoic acid derivatives were prepared as part of a search for subtype-selective human peroxisome proliferator activated receptor α (PPARα) activators. Structure−activity relationship studies indicated that the nature and the stereochemistry of the substituent at the α-position of the head part containing the carboxyl group, the distance between the carboxyl group and the central benzene ring, the linking group between the central benzene ring and the distal benzene ring, and the substituent at the distal hydrophobic tail part of the molecule all play key roles in determining the potency and selectivity of PPAR subtype transactivation. This study has led to the identification of potent and human PPARα selective optically active α-alkylphenylpropanoic acid derivatives, which will be useful not only as pharmacological tools to investigate the physiology and pathophysiology of PPARα but also as candidate drugs for the treatment of altered metabolic homeostasis, such as dyslipidemia, obesi...