Synthesis and pharmacological validation of a novel series of non-steroidal FXR agonists

Bioorganic & Medicinal Chemistry Letters
Ulrich AbelClaus Kremoser

Abstract

To overcome the known liabilities of GW4064 a series of analogs were synthesized where the stilbene double bond is replaced by an oxymethylene or amino-methylene linker connecting a terminal benzoic acid with a substituted heteroaryl in the middle ring position. As a result we discovered compounds with increased potency in vitro that cause dose-dependent reduction of plasma triglycerides and cholesterol in db/db mice down to 2 x 1 mg/kg/day upon oral administration.

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Citations

Oct 16, 2013·Nature Reviews. Gastroenterology & Hepatology·Vlad Ratziu
May 3, 2012·Journal of Lipid Research·Geoffrey PorezBart Staels
Aug 29, 2013·Nature Reviews. Gastroenterology & Hepatology·Frank G SchaapPeter L M Jansen
Jun 2, 2012·Future Medicinal Chemistry·Daniel MerkManfred Schubert-Zsilavecz
Nov 23, 2013·Expert Opinion on Drug Discovery·Daniel MerkManfred Schubert-Zsilavecz
Jun 2, 2012·Drug Discovery Today·Luciano AdoriniDavid Shapiro
Nov 5, 2014·International Journal of Cancer. Journal International Du Cancer·Ulrich DeuschleClaus Kremoser
Feb 22, 2011·Journal of Hepatology·Zhipeng MengWendong Huang
Dec 18, 2013·Molecular Aspects of Medicine·Anna BaghdasaryanMichael Trauner
Sep 28, 2018·Expert Opinion on Therapeutic Patents·Hong WangHaiping Hao
Dec 11, 2014·World Journal of Gastroenterology : WJG·Alessandro FedericoCarmela Loguercio
Jan 10, 2017·Gastroenterology·Jan Freark de BoerAlbert K Groen

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