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, obesity, and diabetes.
| Original language | English |
|---|---|
| Pages (from-to) | 3581-3599 |
| Number of pages | 19 |
| Journal | Journal of Medicinal Chemistry |
| Volume | 46 |
| Issue number | 17 |
| DOIs | |
| Publication status | Published - Aug 14 2003 |
| Externally published | Yes |
Fingerprint
ASJC Scopus subject areas
- Organic Chemistry
Cite this
Design, synthesis, and evaluation of substituted phenylpropanoic acid derivatives as human peroxisome proliferator activated receptor activators. Discovery of potent and human peroxisome proliferator activated receptor α subtype-selective activators. / Nomura, Masahiro; Tanase, Takahiro; Ide, Tomohiro; Tsunoda, Masaki; Suzuki, Masahiro; Uchiki, Hideharu; Murakami, Koji; Miyachi, Hiroyuki.
In: Journal of Medicinal Chemistry, Vol. 46, No. 17, 14.08.2003, p. 3581-3599.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Design, synthesis, and evaluation of substituted phenylpropanoic acid derivatives as human peroxisome proliferator activated receptor activators. Discovery of potent and human peroxisome proliferator activated receptor α subtype-selective activators
AU - Nomura, Masahiro
AU - Tanase, Takahiro
AU - Ide, Tomohiro
AU - Tsunoda, Masaki
AU - Suzuki, Masahiro
AU - Uchiki, Hideharu
AU - Murakami, Koji
AU - Miyachi, Hiroyuki
PY - 2003/8/14
Y1 - 2003/8/14
N2 - 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, obesity, and diabetes.
AB - 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, obesity, and diabetes.
UR - http://www.scopus.com/inward/record.url?scp=0042732947&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0042732947&partnerID=8YFLogxK
U2 - 10.1021/jm0205144
DO - 10.1021/jm0205144
M3 - Article
C2 - 12904063
AN - SCOPUS:0042732947
VL - 46
SP - 3581
EP - 3599
JO - Journal of Medicinal Chemistry
JF - Journal of Medicinal Chemistry
SN - 0022-2623
IS - 17
ER -