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Upstream product

• 278597-32-3 3-(2,6-dichlorophenyl)-4-(3'-chloro-4'-formylphenoxy)-methyl-5-isopropyl-isoxazole 
• 56069-35-3 ethyl 2-chloro-4-hydroxybenzoate 
• 56363-84-9 2-chloro-4-hydroxybenzoic acid 
• 278597-30-1 [3-(2,6-dichlorophenyl)-5-(propan-2-yl)-1,2-oxazol-4-yl]methanol 
• 278597-28-7 methyl 3-(2,6-dichlorophenyl)-5-(propan-2-yl)-1,2-oxazole-4-carboxylate 
• 6579-27-7 2,6-dichlorobenzohydroximoyl chloride 
• 25185-95-9 2,6-dichlorobenzaldoxime 
• 83-38-5 2,6-dichlorobenzaldehyde 

Relevant academic research and scientific papers

Design and Structural Optimization of Dual FXR/PPARδActivators

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.

FARNESOID X RECEPTOR AGONISTS

The invention relates to a compound of formula (I) useful as an agonist for FXR: wherein all variables are as defined herein and to pharmaceutical compositions, methods of using, and processes for preparing the same.