Synthesis and SAR of selective benzothiophene, benzofuran, and indole-based peroxisome proliferator-activated receptor delta agonists.

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Filzen GF, Bratton L, Cheng XM, Erasga N, Geyer A, Lee C, Lu G, Pulaski J, Sorenson RJ, Unangst PC, Trivedi BK, Xu X

Synthesis and SAR of selective benzothiophene, benzofuran, and indole-based peroxisome proliferator-activated receptor delta agonists.

Bioorg Med Chem Lett. 2007 Jul 1;17(13):3630-5. Epub 2007 Apr 24.

PubMed ID

17512197 [ View in PubMed

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Abstract

Recent literature has suggested the benefit of selective PPARdelta agonists for the treatment of atherosclerosis and other disease states associated with the metabolic syndrome. Herein we report the synthesis and structure-activity relationships of a series of novel and selective PPARdelta agonists. Our search began with identification of a novel benzothiophene template which was modified by the addition of various thiazolyl, isoxazolyl, and benzyloxy-benzyl moieties. Further elucidation of the SAR led to the identification of benzofuran and indole based templates. During the course of our research, we discovered three new chemical templates with varying degrees of affinity and potency for PPARdelta versus the PPARalpha and PPARgamma subtypes.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Cardarine	Peroxisome proliferator-activated receptor alpha	IC 50 (nM)	463	N/A	N/A	Details
Cardarine	Peroxisome proliferator-activated receptor delta	IC 50 (nM)	2.6	N/A	N/A	Details
Cardarine	Peroxisome proliferator-activated receptor delta	EC 50 (nM)	4	N/A	N/A	Details