543713-03-7

Basic information

• Product Name: N-hydroxy-2-(trifluoromethoxy)benzimidonyl chloride
• Synonyms: N-hydroxy-2-(trifluoromethoxy)benzimidonyl chloride
• CAS NO: 543713-03-7
• Molecular Weight: 239.581
• Mol File: 543713-03-7.mol
• Article Data: 14

Chemical Properties

• CAS DataBase Reference: N-hydroxy-2-(trifluoromethoxy)benzimidonyl chloride(CAS DataBase Reference)
• NIST Chemistry Reference: N-hydroxy-2-(trifluoromethoxy)benzimidonyl chloride(543713-03-7)
• EPA Substance Registry System: N-hydroxy-2-(trifluoromethoxy)benzimidonyl chloride(543713-03-7)

Safety Data

• Hazardous Substances Data: 543713-03-7(Hazardous Substances Data)

Upstream product

• 255820-47-4 2-(trifluoromethoxy)benzoaldehyde oxime 
• 94651-33-9 2-(trifluoromethoxy)benzaldehyde 
• 1383740-00-8 (E)-2-(trifluoromethoxy)benzaldehyde oxime 

Downstream Products

• 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 
• 1383740-02-0 tert-butyl 4-((5-cyclopropyl-3-(2-(trifluoromethoxy)phenyl)isoxazol-4-yl)methoxy)piperidine-1-carboxylate 
• 1383739-48-7 ethyl 2-(4-((5-cyclopropyl-3-(2-(trifluoromethoxy)phenyl)isoxazol-4-yl)methoxy)piperidin-1-yl)benzo[d]thiazole-6-carboxylate 
• 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 
• 1103500-51-1 tert-butyl 4-((5-cyclopropyl-3-(2-(trifluoromethoxy)phenyl)isoxazol-4-yl)methoxy)azepane-1-carboxylate 
• 1383739-76-1 C₃₀H₃₀F₃N₃O₅S 
• 1383816-29-2 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 
• 1383739-49-8 2-(4-((5-cyclopropyl-3-(2-(trifluoromethoxy)phenyl)isoxazol-4-yl)methoxy)piperidin-1-yl)benzo[d]thiazole-6-carboxylic acid 
• 1383739-77-2 2-(4-((5-cyclopropyl-3-(2-(trifluoromethoxy)phenyl)isoxazol-4-yl)methoxy)azepan-1-yl)benzo[d]thiazole-6-carboxylic acid 
• 1383818-47-0 methyl 2-(3-((5-cyclopropyl-3-(2-(trifluoromethoxy)phenyl)isoxazol-4-yl)methoxy)-8-azabicyclo[3.2.1]octan-8-yl)-4-methylbenzo[d]thiazole-6-carboxylate 
• 1383818-48-1 2-(3-((5-cyclopropyl-3-(2-(trifluoromethoxy)phenyl)isoxazol-4-yl)methoxy)-8-azabicyclo[3.2.1]octan-8-yl)-4-methylbenzo[d]thiazole-6-carboxylic acid 
• 1383816-32-7 methyl 2-(3-((5-cyclopropyl-3-(2-(trifluoromethoxy)phenyl)isoxazol-4-yl)methoxy)-8-azabicyclo[3.2.1]octan-8-yl)-4-methoxybenzo[d]thiazole-6-carboxylate 
• 1383816-33-8 2-(3-((5-cyclopropyl-3-(2-(trifluoromethoxy)phenyl)isoxazol-4-yl)methoxy)-8-azabicyclo[3.2.1]octan-8-yl)-4-methoxybenzo[d]thiazole-6-carboxylic acid 
• 946427-86-7 4-(bromomethyl)-5-cyclopropyl-3-(2-(trifluoromethoxy)phenyl)isoxazole 

Relevant articles and documents

Isoxazole FXR receptor agonist as well as preparation method and medical application thereof

The invention belongs to the field of medicinal chemistry, and particularly relates to an isoxazole FXR receptor agonist and a preparation method and medical application thereof. The invention relates to a compound as shown in a formula (I), and pharmaceutically acceptable salts and isotope markers thereof. The compound as shown in the formula (I), the pharmaceutically acceptable salts and the isotope markers thereof have FXR receptor agonist activity and can be applied to preparation of drugs for treating or preventing hyperlipidemia, atherosclerosis, non-alcoholic steatohepatitis and type II diabetes mellitus.

Structure-guided modification of isoxazole-type FXR agonists: Identification of a potent and orally bioavailable FXR modulator

Farnesoid X receptor (FXR) agonists are emerging as potential therapeutics for the treatment of various metabolic diseases, as they display multiple effects on bile acid, lipid, and glucose homeostasis. Although the steroidal obeticholic acid, a full FXR agonist, was recently approved, several side effects probably due to insufficient pharmacological selectivity impede its further clinical application. Activating FXR in a partial manner is therefore crucial in the development of novel FXR modulators. Our efforts focusing on isoxazole-type FXR agonists, common nonsteroidal agonists for FXR, led to the discovery a series of novel FXR agonists bearing aryl urea moieties through structural simplification of LJN452 (phase 2). Encouragingly, compound 11k was discovered as a potent FXR agonist which exhibited similar FXR agonism potency but lower maximum efficacy compared to full agonists GW4064 and LJN452 in cell-based FXR transactivation assay. Extensive in vitro evaluation further confirmed partial efficacy of 11k in cellular FXR-dependent gene modulation, and revealed its lipid-reducing activity. More importantly, orally administration of 11k in mice exhibited desirable pharmacokinetic characters resulting in promising in vivo FXR agonistic activity.

Discovery and Optimization of Non-bile Acid FXR Agonists as Preclinical Candidates for the Treatment of Nonalcoholic Steatohepatitis

Farnesoid X receptor (FXR) plays a key role in bile acid homeostasis, inflammation, fibrosis, and metabolism of lipid and glucose and becomes a promising therapeutic target for nonalcoholic steatohepatitis (NASH) or other FXR-dependent diseases. The phase III trial results of obeticholic acid demonstrate that the FXR agonists emerge as a promising intervention in patients with NASH and fibrosis, but this bile acid-derived FXR agonist brings severe pruritus and an elevated risk of cardiovascular disease for patients. Herein, we reported our efforts in the discovery of a series of non-bile acid FXR agonists, and 36 compounds were designed and synthesized based on the structure-based drug design and structural optimization strategies. Particularly, compound 42 is a highly potent and selective FXR agonist, along with good pharmacokinetic profiles, high liver distribution, and preferable in vivo efficacy, indicating that it is a potential candidate for the treatment of NASH or other FXR-dependent diseases.