104437-17-4Relevant articles and documents
Dual Farnesoid X Receptor/Soluble Epoxide Hydrolase Modulators Derived from Zafirlukast
Schierle, Simone,Helmst?dter, Moritz,Schmidt, Jurema,Hartmann, Markus,Horz, Maximiliane,Kaiser, Astrid,Weizel, Lilia,Heitel, Pascal,Proschak, Anna,Hernandez-Olmos, Victor,Proschak, Ewgenij,Merk, Daniel
, p. 50 - 67 (2020)
The nuclear farnesoid X receptor (FXR) and the enzyme soluble epoxide hydrolase (sEH) are validated molecular targets to treat metabolic disorders such as non-alcoholic steatohepatitis (NASH). Their simultaneous modulation in vivo has demonstrated a triad of anti-NASH effects and thus may generate synergistic efficacy. Here we report dual FXR activators/sEH inhibitors derived from the anti-asthma drug Zafirlukast. Systematic structural optimization of the scaffold has produced favorable dual potency on FXR and sEH while depleting the original cysteinyl leukotriene receptor antagonism of the lead drug. The resulting polypharmacological activity profile holds promise in the treatment of liver-related metabolic diseases.
Indole and indazole keto sulphones as leukotriene antagonists
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, (2008/06/13)
This invention provides a series of novel keto sulfones of formula I STR1 in which the group =A-- is selected from =C(Ra)-- and =N-- and the other radicals have the meanings defined in the following specification. The compounds of formula I are leukotriene antagonists. The invention also provides pharmaceutically acceptable salts of the formula I compounds; pharmaceutical compositions containing the formula I compound, or their salts, for use in the treatment of, for example, allergic or inflammatory diseases, or endotoxic or traumatic shock conditions; and processes for the manufacture of the formula I compounds, as well as intermediates for use in such manufacture.