(2R)-2-ethylchromane-2-carboxylic acids: discovery of novel PPARalpha/gamma dual agonists as antihyperglycemic and hypolipidemic agents.

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Koyama H, Miller DJ, Boueres JK, Desai RC, Jones AB, Berger JP, MacNaul KL, Kelly LJ, Doebber TW, Wu MS, Zhou G, Wang PR, Ippolito MC, Chao YS, Agrawal AK, Franklin R, Heck JV, Wright SD, Moller DE, Sahoo SP

(2R)-2-ethylchromane-2-carboxylic acids: discovery of novel PPARalpha/gamma dual agonists as antihyperglycemic and hypolipidemic agents.

J Med Chem. 2004 Jun 3;47(12):3255-63.

PubMed ID

15163205 [ View in PubMed

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Abstract

A series of chromane-2-carboxylic acid derivatives was synthesized and evaluated for PPAR agonist activities. A structure-activity relationship was developed toward PPARalpha/gamma dual agonism. As a result, (2R)-7-(3-[2-chloro-4-(4-fluorophenoxy)phenoxy]propoxy)-2-ethylchromane-2-carboxy lic acid (48) was identified as a potent, structurally novel, selective PPARalpha/gamma dual agonist. Compound 48 exhibited substantial antihyperglycemic and hypolipidemic activities when orally administered in three different animal models: the db/db mouse type 2 diabetes model, a Syrian hamster lipid model, and a dog lipid model.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Rosiglitazone	Peroxisome proliferator-activated receptor alpha	IC 50 (nM)	15000	N/A	N/A	Details
Rosiglitazone	Peroxisome proliferator-activated receptor gamma	EC 50 (nM)	20	N/A	N/A	Details
Rosiglitazone	Peroxisome proliferator-activated receptor gamma	IC 50 (nM)	200	N/A	N/A	Details