2-Alkoxydihydrocinnamates as PPAR agonists. Activity modulation by the incorporation of phenoxy substituents.

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Martin JA, Brooks DA, Prieto L, Gonzalez R, Torrado A, Rojo I, Lopez de Uralde B, Lamas C, Ferritto R, Dolores Martin-Ortega M, Agejas J, Parra F, Rizzo JR, Rhodes GA, Robey RL, Alt CA, Wendel SR, Zhang TY, Reifel-Miller A, Montrose-Rafizadeh C, Brozinick JT, Hawkins E, Misener EA, Briere DA, Ardecky R, Fraser JD, Warshawsky AM

2-Alkoxydihydrocinnamates as PPAR agonists. Activity modulation by the incorporation of phenoxy substituents.

Bioorg Med Chem Lett. 2005 Jan 3;15(1):51-5.

PubMed ID

15582409 [ View in PubMed

]

Abstract

Herein we describe a series of potent and selective PPARgamma agonists with moderate PPARalpha affinity and little to no affinity for other nuclear receptors. In vivo studies in a NIDDM animal model (ZDF rat) showed that these compounds are efficacious at low doses in glucose normalization and plasma triglyceride reduction. Compound 1b (LY519818) was selected from our SAR studies to be advanced to clinical evaluation for the treatment of type II diabetes.

DrugBank Data that Cites this Article

Drugs

Naveglitazar

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Rosiglitazone	Peroxisome proliferator-activated receptor alpha	IC 50 (nM)	>10000	N/A	N/A	Details
Rosiglitazone	Peroxisome proliferator-activated receptor gamma	IC 50 (nM)	70	N/A	N/A	Details
Rosiglitazone	Peroxisome proliferator-activated receptor gamma	EC 50 (nM)	268	N/A	N/A	Details