259269-55-1Relevant academic research and scientific papers
A New FXR Ligand Chemotype with Agonist/Antagonist Switch
Helmst?dter, Moritz,Vietor, Jan,Sommer, Jana,Schierle, Simone,Willems, Sabine,Kaiser, Astrid,Schmidt, Jurema,Merk, Daniel
, p. 267 - 274 (2021)
Therapeutic modulation of the bile acid-sensing transcription factor farnesoid X receptor (FXR) is an appealing strategy to counteract hepatic and metabolic diseases. Despite the availability of several highly potent FXR agonists structural diversity of FXR modulators is limited, and new ligand scaffolds are needed. Here we report structure-activity relationship elucidation of a new FXR modulator chemotype whose activity can be tuned between agonism and antagonism by two minor structural modifications. Starting from a weak FXR/PPAR agonist, we have developed selective FXR activators and antagonists with nanomolar to low-micromolar potencies and binding affinities. The new FXR ligand chemotype modulates the FXR activity in the native cellular setting, is endowed with favorable metabolic stability, and lacks cytotoxicity. It valuably expands the collection of FXR modulators as a new scaffold for FXR-targeted drug discovery.
PYRROLE DERIVATIVES
-
Page/Page column 28; 29, (2017/11/04)
Provided herein are compounds of the formula (I) : as well as pharmaceutically acceptable salts thereof, wherein the substituents are as those disclosed in the specification. These compounds, and the pharmaceutical compositions containing them, are useful
Synthesis of 1-(4-trifluoromethoxyphenyl)-2,5-dimethyl-3-(2-rthiazol-4-yl)- 1H-pyrroles via chain heterocyclization
Vovk, Mykhaylo V.,Pinchuk, Oleksandr M.,Tolmachov, Andrij O.,Gakh, Andrei A.
experimental part, p. 997 - 1006 (2010/04/29)
The title compounds, (4-trifluoromethoxyphenyl)-2,5-dimethyl-3-(2-R- thiazol- 4-yl)-1H-pyrroles, were prepared in four steps starting from commercially available 4- trifluoromethoxyaniline. The pyrrole (second ring) was added in one step using the Paal- K
