227290-22-4Relevant academic research and scientific papers
Design, Synthesis, and Structure-Activity Relationship Studies of Dual Inhibitors of Soluble Epoxide Hydrolase and 5-Lipoxygenase
Hiesinger, Kerstin,Kramer, Jan S.,Beyer, Sandra,Eckes, Timon,Brunst, Steffen,Flauaus, Cathrin,Wittmann, Sandra K.,Weizel, Lilia,Kaiser, Astrid,Kretschmer, Simon B. M.,George, Sven,Angioni, Carlo,Heering, Jan,Geisslinger, Gerd,Schubert-Zsilavecz, Manfred,Schmidtko, Achim,Pogoryelov, Denys,Pfeilschifter, Josef,Hofmann, Bettina,Steinhilber, Dieter,Schwalm, Stephanie,Proschak, Ewgenij
, p. 11498 - 11521 (2020)
Inhibition of multiple enzymes of the arachidonic acid cascade leads to synergistic anti-inflammatory effects. Merging of 5-lipoxygenase (5-LOX) and soluble epoxide hydrolase (sEH) pharmacophores led to the discovery of a dual 5-LOX/sEH inhibitor, which was subsequently optimized in terms of potency toward both targets and metabolic stability. The optimized lead structure displayed cellular activity in human polymorphonuclear leukocytes, oral bioavailability, and target engagement in vivo and demonstrated profound anti-inflammatory and anti-fibrotic efficiency in a kidney injury model caused by unilateral ureteral obstruction in mice. These results pave the way for investigating the therapeutic potential of dual 5-LOX/sEH inhibitors in other inflammation- and fibrosis-related disease models.
DUAL INHIBITORS OF SOLUBLE EPOXIDE HYDROLASE AND 5-LIPOXYGENASE
-
Paragraph 107-108; 236-237; 247, (2021/10/30)
The invention pertains to a novel structure (I) that provides an activity as a dual inhibitor of the enzymes soluble epoxide hydrolase (sEH) and 5-lipoxygenase (5-LOX). The invention pertains to multiple derivatives of the new class of dual inhibitors, their application in medicine, pharmaceutical compositions comprising them as well as to methods for synthesizing the new compounds.
Anticonvulsant and central nervous system-depressing bis(fluorophenyl)alkylamides and their uses
-
, (2008/06/13)
Bis(Fluorophenyl)alkylamides have been chemically synthesized which possess beneficial pharmacological properties (e.g., anticonvulsant activity) useful for the treatment of neurological diseases or disorders, such as, for example, epilepsy, convulsions, and seizure disorders. The preferred compounds of the invention also cause little sedation and have high therapeutic and protective indices in animal models of epilepsy. These compounds further possess long pharmacological half-lives, which, in practical clinical therapeutic application, should translate into once-a-day dosing, of great benefit to patients suffering from these diseases and/or disorders. These compounds may also be of further clinical utility in the treatment of other diseases and disorders of the central and peripheral nervous systems, or diseases or disorders affected by them, including, but not limited to, spasticity, skeletal muscle spasms and pain, restless leg syndrome, anxiety and stress, and bipolar disorder.
