62889-60-5Relevant academic research and scientific papers
Design and Structural Optimization of Dual FXR/PPARδActivators
Schierle, Simone,Neumann, Sebastian,Heitel, Pascal,Willems, Sabine,Kaiser, Astrid,Pollinger, Julius,Merk, Daniel
, p. 8369 - 8379 (2020)
Nonalcoholic steatohepatitis (NASH) is considered as severe hepatic manifestation of the metabolic syndrome and has alarming global prevalence. The ligand-activated transcription factors farnesoid X receptor (FXR) and peroxisome proliferator-activated receptor (PPAR) δhave been validated as molecular targets to counter NASH. To achieve robust therapeutic efficacy in this multifactorial pathology, combined peripheral PPAR?-mediated activity and hepatic effects of FXR activation appear as a promising multitarget approach. We have designed a minimal dual FXR/PPARδactivator scaffold by rational fusion of pharmacophores derived from selective agonists. Our dual agonist lead compound exhibited weak agonism on FXR and PPARδand was structurally refined to a potent and balanced FXR/PPARδactivator in a computer-aided fashion. The resulting dual FXR/PPARδmodulator comprises high selectivity over related nuclear receptors and activates the two target transcription factors in native cellular settings.
Dibenz[b,e]oxepinalkanoic acids as nonsteroidal antiinflammatory agents. 3. ω (6,11 Dihydro 11 oxodibenz[b,e]oxepin 2 yl)alkanoic acids
Aultz,McFadden,Lassman
, p. 1499 - 1501 (2007/10/13)
ω-(6,11-Dihydro-11-oxodibenz[b,e]oxepin-2-yl)butyric,-hexanoic, and -octanoic acids were evaluated in the carrageenan paw edema assay. The most active compound, the butyric acid analogue, was 1.80 times more potent than the hexanoic compound, 1.15 times m
