74467-04-2

Basic information

• Product Name: N-HYDROXY-2-(TRIFLUOROMETHYL)BENZENECARBOXIMIDOYL CHLORIDE
• Synonyms: N-HYDROXY-2-(TRIFLUOROMETHYL)BENZENECARBOXIMIDOYL CHLORIDE;N-hydroxy-2-(trifluoroMethoxy)benzene carboxiMidoyl chloride;N-Hydroxy-2-(trifluoromethyl)benzimidoyl chloride
• CAS NO: 74467-04-2
• Molecular Formula: C₈H₅ClF₃NO
• Molecular Weight: 223.5796096
• Mol File: 74467-04-2.mol

Chemical Properties

• Melting Point: 80-82
• Boiling Point: 286.8°C at 760 mmHg
• Flash Point: 127.3°C
• Appearance: /
• Density: 1.41g/cm³
• Vapor Pressure: 0.0012mmHg at 25°C
• Refractive Index: 1.487
• CAS DataBase Reference: N-HYDROXY-2-(TRIFLUOROMETHYL)BENZENECARBOXIMIDOYL CHLORIDE(CAS DataBase Reference)
• NIST Chemistry Reference: N-HYDROXY-2-(TRIFLUOROMETHYL)BENZENECARBOXIMIDOYL CHLORIDE(74467-04-2)
• EPA Substance Registry System: N-HYDROXY-2-(TRIFLUOROMETHYL)BENZENECARBOXIMIDOYL CHLORIDE(74467-04-2)

Safety Data

• Hazard Codes: Xi
• HazardClass: IRRITANT
• Hazardous Substances Data: 74467-04-2(Hazardous Substances Data)

Usage

InChI:InChI=1/C8H5ClF3NO/c9-7(13-14)5-3-1-2-4-6(5)8(10,11)12/h1-4,14H/b13-7-

Upstream product

• 74467-00-8 N-[[2-(trifluoromethyl)phenyl]methylidene]hydroxylamine 
• 447-61-0 2-Trifluoromethylbenzaldehyde 

Downstream Products

• 76272-14-5 3'-<2''-(trifluoromethyl)phenyl>spiro-3-one 
• 1325731-29-0 3-(2-(trifluoromethyl)phenyl)-1-oxa-2,7,11-triazaspiro[4.11]hexadec-2-ene-6,12,16-trione 
• 1352191-60-6 5-((2,6-difluorobenzyloxy)methyl)-5-methyl-3-(2-(trifluoromethyl)phenyl)-4,5-dihydroisoxazole 
• 1402881-77-9 methyl 5-methyl-3-(2-(trifluoromethyl)phenyl)isoxazole-4-carboxylate 
• 1353749-31-1 C₂₀H₂₁F₃N₂O₃ 
• 1353749-30-0 C₂₂H₁₉F₃N₂O₃ 
• 1353749-29-7 C₁₇H₁₆F₃N₃O₄ 
• 1353749-28-6 C₁₇H₁₇F₃N₂O₄ 
• 1350470-11-9 4-(3-(2-(trifluoromethyl)phenyl)isoxazol-5-yl)benzonitrile 
• 1312713-63-5 1-(8-(4-chlorophenyl)-3-(2-(trifluoromethyl)phenyl)-1-oxa-2,7,8-triazaspiro[4.4]non-2-en-7-yl)ethanone 
• 1312713-55-5 (4-(tert-butyl)phenyl)(8-isopropyl-3-(2-(trifluoromethyl)-phenyl)-1-oxa-2,7,8-triazaspiro[4.4]non-2-en-7-yl)methanone 
• 1312713-59-9 furan-2-yl(8-isopropyl-3-(2-(trifluoromethyl)phenyl)-1-oxa-2,7,8-triazaspiro[4.4]non-2-en-7-yl)methanone 
• 901926-66-7 3-[2-(trifluoromethyl)phenyl]isoxazole-5-carboxylic acid 
• 377063-78-0 ethyl 3-[2-(trifluoromethyl)phenyl]isoxazole-5-carboxylate 

Relevant articles and documents

Design and synthesis of sinomenine isoxazole derivatives via 1,3-dipolar cycloaddition reaction

A novel structure of sinomenine isoxazole derivatives is synthesised from sinomenine hydrochloride and aromatic aldehydes and requires six steps. 19 target compounds have been obtained in good yields. The sinomenine hydrochloride transforms to 4-alkynyl sinomenine, which is a key intermediate product to synthesise the target sinomenine isoxazole compounds, after a neutralisation reaction with ammonia and substitution reaction with 3-chloropropyne. Another key intermediate product is 1,3-dipole, which can be obtained from aromatic aldehyde. After treatment with hydroxylamine hydrochloride and then sodium carbonate solution, aromatic aldehyde is converted to aldehyde oxime, which reacts with N-chlorosuccinimide (NCS) to afford aryl hydroximino chloride. 1,3-Dipole is eventually formed in situ while triethylamine (TEA) in DMF is added dropwise. Then 4-alkynyl sinomenine is added to provide the sinomenine isoxazole derivative via 1,3-dipolar cycloaddition reaction as the key step. All the target compounds are characterised by melting point, 1H NMR, 13C NMR, HRMS and FT-IR spectroscopy.

Discovery of BMS-986318, a Potent Nonbile Acid FXR Agonist for the Treatment of Nonalcoholic Steatohepatitis

Herein we report the discovery and preclinical biological evaluation of 6-(2-(5-cyclopropyl-3-(3,5-dichloropyridin-4-yl)isoxazol-4-yl)-7-azaspiro[3.5]non-1-en-7-yl)-4-(trifluoromethyl)quinoline-2-carboxylic acid, compound 1 (BMS-986318), a nonbile acid farnesoid X receptor (FXR) agonist. Compound 1 exhibits potent in vitro and in vivo activation of FXR, has a suitable ADME profile, and demonstrates efficacy in the mouse bile duct ligation model of liver cholestasis and fibrosis. The overall profile of compound 1 supports its continued evaluation.

ISOXAZOLE DERIVATIVES AND PREPARATION PROCESS THEREOF

The present invention relates to an isoxazole derivative compound of Formula (1) useful as a substance for treating respiratory viral infectious disease caused by coronavirus, in particular, Middle East respiratory syndrome-coronavirus (MERS-CoV); a pharm

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.

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.

Identification of morpholine based hydroxylamine analogues: Selective inhibitors of MARK4/Par-1d causing cancer cell death through apoptosis

Microtubule affinity-regulating kinase 4 (MARK4) is a serine/threonine kinase involved in the phosphorylation of MAP proteins that regulates microtubule dynamics and abets tumor progression by participating in oncogenic signaling pathways. It is overexpressed in multiple human malignancies and no drug is available for this potential therapeutic target at present. Therefore, using the structure based drug design strategy, a library of hydroxylamine derivatives of morpholine were designed and synthesized as small molecule inhibitors of MARK4. Compound 32 having the CF3 group at the ortho position of the phenyl ring tethered with the >CNOH core and the hinge binder morpholine component was found to be a potent and selective inhibitor of MARK4 over thirty other serine-threonine kinases. Study of cell viability and compound induced morphological changes in MCF-7 cancer cells discovered that molecule 32 caused death of cancerous cells through the mechanism of apoptosis. Compound 32 may be transported and delivered to the target site through the blood stream, and has promising antioxidant potential. Such bio-active molecules could serve as optimized lead candidates in drug discovery for cancer treatment through MARK4 inhibition.

COMPOUNDS FOR MODULATING FXR

Provided herein are compounds of Formula (I), a stereoisomer, enantiomer or a pharmaceutically acceptable salt thereof; wherein variables are as defined herein; and their pharmaceutical compositions, which are useful as modulators of the activity of Farnesoid X receptors (FXR).

MULTICYCLIC COMPOUNDS AS FARNESOID X RECEPTOR MODULATORS

The present invention provides compounds of Formula (I), or stereoisomers, tautomers, or pharmaceutically acceptable salts or solvates thereof, wherein all the variables are as defined herein. These compounds modulate the activity of farnesoid X receptor (FXR), for example, as agonists. This invention also relates to pharmaceutical compositions comprising these compounds and methods of treating a disease, disorder, or condition associated with FXR dysregulation, such as pathological fibrosis, transplant rejection, cancer, osteoporosis, and inflammatory disorders, by using the compounds and pharmaceutical compositions.

HORMONE RECEPTOR MODULATORS FOR TREATING METABOLIC CONDITIONS AND DISORDERS

The invention relates to activators of FXR useful in the treatment of autoimmune disorders, liver disease, intestinal disease, kidney disease, cancer, and other diseases in which FXR plays a role, having the Formula (I): (I), wherein L1, A, X1, X2, R1, R2, and R3 are described herein.

AN ISOXAZOLE DERIVATIVES AS NUCLEAR RECEPTOR AGONISTS AND USED THEREOF

The present invention relates to isoxazole derivatives, including pharmaceutical compositions and for the preparation of isoxazole derivatives. And more particularly the present invention provided a pharmaceutical composition of isoxazole derivatives for activation of Farnesoid X receptor(FXR, NR1H4).