Nonacidic Farnesoid X Receptor Modulators

被引：69

作者：

Flesch, Daniel ^{[1
]}

Cheung, Sun-Yee ^{[1
]}

Schmidt, Jurema ^{[1
]}

Gabler, Matthias ^{[1
]}

Heitel, Pascal ^{[1
]}

Kramer, Jan ^{[1
]}

Kaiser, Astrid ^{[1
]}

Hartmann, Markus ^{[1
]}

Lindner, Mara ^{[3
]}

Lueddens-Daemgen, Kerstin ^{[2
]}

Heering, Jan ^{[3
]}

Lamers, Christina ^{[1
]}

Lueddens, Hartmut ^{[2
]}

Wurglics, Mario ^{[1
]}

Proschak, Ewgenij ^{[1
]}

Schubert-Zsilavecz, Manfred ^{[1
]}

Merk, Daniel ^{[1
]}

机构：

[1] Goethe Univ Frankfurt, Inst Pharmaceut Chem, Max von Laue Str 9, D-60438 Frankfurt, Germany

[2] Univ Med Ctr Mainz, Dept Psychiat & Psychotherapy, D-55131 Mainz, Germany

[3] Fraunhofer Inst Mol Biol & Appl Ecology IME, Project Grp Translat Med & Pharmacol TMP, Theodor Stern Kai 7, D-60596 Frankfurt, Germany

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2017年 / 60卷 / 16期

关键词：

MEDICINAL CHEMISTRY; OBETICHOLIC ACID; FXR; AGONIST; POTENT; DISCOVERY; INSIGHTS; LIGANDS; IDENTIFICATION; DERIVATIVES;

D O I：

10.1021/acs.jmedchem.7b00903

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

As a cellular bile acid sensor, farnesoid X receptor (FXR) participates in regulation of bile acid, lipid and glucose homeostasis, and liver protection. Clinical results have validated FXR as therapeutic target in hepatic and metabolic diseases. To date, potent FXR agonists share a negatively ionizable function that might compromise their pharmacokinetic distribution and behavior. Here we report the development and characterization of a high-affinity FXR modulator not comprising an acidic residue.

引用

页码：7199 / 7205

页数：7

共 34 条

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