1383816-29-2

Basic information

• Product Name: Tropifexor
• Synonyms: Tropifexor;Tropifexor (LJN452);LJN452;LJN452,Tropifexor;2-[(1R,3r,5S)-3-({5-cyclopropyl-3-[2-(trifluoromethoxy)phenyl]-1,2-oxazol-4-yl}methoxy)-8-azabicyclo[3.2.1]octan-8-yl]-4-fluoro-1,3-benzothiazole-6-carboxylic acid;1383816-29-2
• CAS NO: 1383816-29-2
• Molecular Formula: C₂₉H₂₅F₄N₃O₅S
• Molecular Weight: 603.5845128
• EINECS: -0
• Product Categories: API
• Mol File: 1383816-29-2.mol

Chemical Properties

• Boiling Point: 700.0±65.0 °C(Predicted)
• Appearance: /
• Density: 1.55±0.1 g/cm3(Predicted)
• PKA: 3.84±0.10(Predicted)
• CAS DataBase Reference: Tropifexor(CAS DataBase Reference)
• NIST Chemistry Reference: Tropifexor(1383816-29-2)
• EPA Substance Registry System: Tropifexor(1383816-29-2)

Safety Data

• Hazardous Substances Data: 1383816-29-2(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
Tropifexor is used as a therapeutic agent for the treatment of cholestatic liver diseases, which are conditions characterized by impaired bile flow and accumulation of bile acids in the liver. It helps in reducing bile acid synthesis, promoting bile secretion, and mitigating liver injury.
Tropifexor is also used as a treatment for nonalcoholic steatohepatitis (NASH), a severe form of nonalcoholic fatty liver disease (NAFLD) that can lead to liver inflammation, fibrosis, and potentially liver failure. By targeting the FXR pathway, Tropifexor modulates various metabolic and inflammatory processes, which can help in reducing liver fat, inflammation, and fibrosis associated with NASH.

Upstream product

• 543713-03-7 N-hydroxy-2-(trifluoromethoxy)benzimidonyl chloride 
• 924287-65-0 methyl 2-bromo-4-fluoro-1,3-benzothiazole-6-carboxylate 
• 1383822-31-8 (1R,3S,5S)-3-({5-cyclopropyl-3-[2-(trifluoromethoxy)phenyl]-1,2-oxazol-4-yl}methoxy)-8-azabicyclo[3.2.1]octane 
• 1383816-28-1 methyl-2-(3-((5-cyclopropyl-3-(2-(trifluoromethoxy)phenyl)isoxazol-4-yl)methoxy)-8-azabicyclo[3.2.1]octan-8-yl)-4-fluorobenzo[d]thiazole-6-carboxylate 
• 403-21-4 3-fluoro-4-nitrobenzoic acid 
• 1383740-01-9 (Z)-N-hydroxy-2-(trifluoromethoxy)benzimidoyl chloride 
• 1383740-00-8 (E)-2-(trifluoromethoxy)benzaldehyde oxime 
• 1103500-32-8 methyl 5-cyclopropyl-3-(2-(trifluoromethoxy)phenyl)isoxazole-4-carboxylate 
• 946427-86-7 4-(bromomethyl)-5-cyclopropyl-3-(2-(trifluoromethoxy)phenyl)isoxazole 
• 924287-64-9 methyl 2-amino-4-fluoro-1,3-benzothiazole-6-carboxylate 
• 185629-32-7 methyl 4-amino-3-fluorobenzene carboxylate 
• 185629-31-6 methyl 3-fluoro-4-nitrobenzoate 
• 94651-33-9 2-(trifluoromethoxy)benzaldehyde 

Downstream Products

• 1383816-38-3 C₂₉H₂₆F₄N₄O₄S 

Relevant articles and documents

COMBINATIONS COMPRISING BENZODIOXOL AS GLP-1R AGONISTS FOR USE IN THE TREATMENT OF NASH/NAFLD AND RELATED DISEASES

In part, the invention provides a new combination comprising (1) a GLP-1R agonist and (2) an ACC inhibitor or a DGAT2 inhibitor, or a KHK inhibitor or FXR agonist. The invention further provides new methods for treating diseases and disorders, for example, fatty liver, nonalcoholic fatty liver disease, nonalcoholic steatohepatitis, nonalcoholic steatohepatitis with liver fibrosis, nonalcoholic steatohepotitis with cirrhosis, and nonalcoholic steatohepatitis with cirrhosis and with hepatocellular carcinoma or with a metabolic-related disease, obesity, and type 2 diabetes, for example, using the new combination described herein.

Discovery of Tropifexor (LJN452), a Highly Potent Non-bile Acid FXR Agonist for the Treatment of Cholestatic Liver Diseases and Nonalcoholic Steatohepatitis (NASH)

The farnesoid X receptor (FXR) is a nuclear receptor that acts as a master regulator of bile acid metabolism and signaling. Activation of FXR inhibits bile acid synthesis and increases bile acid conjugation, transport, and excretion, thereby protecting the liver from the harmful effects of bile accumulation, leading to considerable interest in FXR as a therapeutic target for the treatment of cholestasis and nonalcoholic steatohepatitis. We identified a novel series of highly potent non-bile acid FXR agonists that introduce a bicyclic nortropine-substituted benzothiazole carboxylic acid moiety onto a trisubstituted isoxazole scaffold. Herein, we report the discovery of 1 (tropifexor, LJN452), a novel and highly potent agonist of FXR. Potent in vivo activity was demonstrated in rodent PD models by measuring the induction of FXR target genes in various tissues. Tropifexor has advanced into phase 2 human clinical trials in patients with NASH and PBC.

COMPOSITIONS AND METHODS FOR MODULATING FXR

The present invention relates to compounds of Formula (I), a stereoisomer, enantiomer, a pharmaceutically acceptable salt or an amino acid conjugate thereof; wherein variables are as defined herein; and their pharmaceutical compositions, which are useful as modulators of the activity of Farnesiod X receptors (FXR).