1383740-01-9

Upstream product

• 94651-33-9 2-(trifluoromethoxy)benzaldehyde 
• 1383740-00-8 (E)-2-(trifluoromethoxy)benzaldehyde oxime 

Downstream Products

• 1103500-32-8 methyl 5-cyclopropyl-3-(2-(trifluoromethoxy)phenyl)isoxazole-4-carboxylate 
• 1383740-02-0 tert-butyl 4-((5-cyclopropyl-3-(2-(trifluoromethoxy)phenyl)isoxazol-4-yl)methoxy)piperidine-1-carboxylate 
• 1383740-03-1 5-cyclopropyl-4-((piperidin-4-yloxy)methyl)-3-(2-(trifluoromethoxy)phenyl)isoxazole 
• 1383743-96-1 4-((5-cyclopropyl-3-(2-(trifluoromethoxy)phenyl)isoxazol-4-yl)methoxy)piperidine-1-carbonitrile 
• 1383783-23-0 (E)-4-((5-cyclopropyl-3-(2-(trifluoromethoxy)phenyl)isoxazol-4-yl)methoxy)-N'-hydroxypiperidine-1-carboximidamide 
• 1383783-24-1 methyl 4-((((amino(4-((5-cyclopropyl-3-(2-(trifluoromethoxy)phenyl)isoxazol-4-yl)methoxy)piperidin-1-yl)methylene)amino)oxy)carbonyl)benzoate 
• 1383743-66-5 methyl 4-(3-(4-((5-cyclopropyl-3-(2-(trifluoromethoxy)phenyl)isoxazol-4-yl)methoxy)piperidin-1-yl)-1,2,4-oxadiazol-5-yl)benzoate 
• 1383743-67-6 4-(3-(4-((5-cyclopropyl-3-(2-(trifluoromethoxy)phenyl)isoxazol-4-yl)methoxy)piperidin-1-yl)-1,2,4-oxadiazol-5-yl)benzoic acid 
• 1383739-48-7 ethyl 2-(4-((5-cyclopropyl-3-(2-(trifluoromethoxy)phenyl)isoxazol-4-yl)methoxy)piperidin-1-yl)benzo[d]thiazole-6-carboxylate 
• 1383817-89-7 6-(3-((5-cyclopropyl-3-(2-(trifluoromethoxy)phenyl)isoxazol-4-yl)methoxy)-8-azabicyclo[3.2.1]octan-8-yl)benzo[d]isothiazole-3-carboxylic acid 
• 1383824-64-3 methyl 6-(3-((5-cyclopropyl-3-(2-(trifluoromethoxy)phenyl)isoxazol-4-yl)methoxy)-8-azabicyclo[3.2.1]octan-8-yl)benzo[d]isothiazole-3-carboxylate 
• 1383817-71-7 4-(3-((5-cyclopropyl-3-(2-(trifluoromethoxy)phenyl)isoxazol-4-yl)methoxy)-8-azabicyclo[3.2.1]octan-8-yl)-3-fluorobenzoic acid 
• 1383817-70-6 methyl 4-(3-((5-cyclopropyl-3-(2-(trifluoromethoxy)phenyl)isoxazol-4-yl)methoxy)-8-azabicyclo[3.2.1]octan-8-yl)-3-fluorobenzoate 
• 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 

Relevant academic research and scientific papers

Discovery of novel ketoxime ether derivatives with potent FXR agonistic activity, oral effectiveness and high liver/blood ratio

The farnesoid X receptor (FXR) is a promising therapeutic target for nonalcoholic steatohepatitis (NASH) and other bile acid related diseases because it plays a critical role in fibrosis, inflammation and bile acid homeostasis. Obeticholic acid (OCA), a FXR agonist which was synthesized from chenodeoxycholic acid, showed desirable curative effects in clinical trials. However, the pruritus which was the main side effect of OCA limited its further applications in NASH. Although pruritus was also observed in the clinical trials of non-steroidal FXR agonists, the proportion of patients with pruritus was much smaller than that of OCA. Thus, we decided to develop non-steroidal FXR agonists and discovered a series of novel FXR agonists which were synthesized from GW4064 by replacing the stilbene group with ketoxime ether. Encouragingly, in the following biological tests, our target compounds 13j and 13z not only showed potent FXR agonistic activities in vitro, but also effectively promoted the expression of target genes in vivo. More importantly, in the pharmacokinetic experiments, compounds 13j and 13z displayed high liver/blood ratio characteristics which were helpful to reduce the potential side effects which were caused by prolonged systemic activation of FXR. In summary, our compounds were good choices for the development of non-steroidal FXR agonists and were deserved further investigation.

FARNESOID X RECEPTOR MODULATING COMPOUNDS AND METHODS OF USING THE SAME

Provided are compounds that can act as a modulator of a farnesoid X receptor (FXR) and that can be useful in the treatment of diseases and/or disorders associated with the FXR. Compositions including such compounds are also provided along with methods for preparing compounds of the present invention and their use.

Isoxazole derivative, pharmaceutical composition containing isoxazole derivative, and preparation method and application thereof

The present invention belongs to the field of pharmaceutical chemistry, and generally relates to an isoxazole derivative, and stereoisomers, tautomers, polymorphs, solvates (such as hydrates), esters, metabolites, N-oxides and chemically protected forms and prodrugs thereof, or pharmaceutically acceptable salts thereof. The invention also relates to a preparation method of the compound, a pharmaceutical composition containing the compound and application of the compound and the pharmaceutical composition in treating diseases or conditions mediated by farnesoid X receptor (FXR).

COMPOUNDS USEFUL IN MODULATING THE FARNESOID X RECEPTOR AND METHODS OF MAKING AND USING THE SAME

Provided are compounds that can act as a modulator of a farnesoid X receptor (FXR) and that can be useful in the treatment of diseases and/or disorders associated with the FXR. Compositions including such compounds are also provided along with methods for preparing compounds of the present invention and their use.

ISOXAZOLE DERIVATIVE, PREPARATION METHOD THEREFOR, AND USE THEREOF

The present invention generally relates to an isoxazole derivative, a preparation therefor, and a use thereof. In particular, the present invention provides a farnesoid X receptor (FXR) agonist compound, and a stereoisomer, a tautomer, a polymorph, a solvate (e.g., a hydrate), a pharmaceutically acceptable salt, an ester, a metabolite, and an N-oxide, and the chemically protected forms and prodrugs thereof. The present invention further provides a preparation method for the compound, an intermediate thereof, and a pharmaceutical composition and kit containing the same and used thereof for treating FXR-mediated diseases or conditions.

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.

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).

COMPOSITIONS AND METHODS FOR MODULATING FARNESOID X RECEPTORS

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).

COMPOSITIONS AND METHODS FOR MODULATING FARNESOID X RECEPTORS

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

FARNESOID X RECEPTOR AGONISTS

The present invention relates to famesoid X receptors (FXR, NR1H4) FXR is a member of the nuclear receptor class of ligand-activate transcription factors More particularly, the present invention relates to compounds useful as agonists for FXR, pharmaceutical formulations comprising such compounds, and therapeutic use of the same Novel isoxazole compounds are disclosed as part of pharmaceutical compositions for the treatment of a condition mediated by decreased FXR activity, such as obesity, diabetes, cholestatic liver disease, liver fibrosis, and metabolic syndrome