107754-54-1Relevant academic research and scientific papers
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 (2019/11/29)
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.
Synthesis and in vitro LTD4 antagonist activity of bicyclic and monocyclic cyclopentylurethane and cyclopentylacetamide N-arylsulfonyl amides
Matassa,Brown,Bernstein,Shapiro,Maduskuie Jr.,Cronk,Vacek,Yee,Snyder,Krell,Lerman,Maloney
, p. 2621 - 2629 (2007/10/02)
The dissociation constants (K(B)) at the LTD4 receptor on guinea pig trachea of a series of monocyclic and bicyclic cyclopentylurathane and cyclopentylacetamide N-arylsulfonyl amides have been measured. The K(B) was found to be remarkably toler
