6579-27-7

Basic information

• Product Name: 2,6-DICHLORO-N-HYDROXYBENZENECARBOXIMIDOYL CHLORIDE
• Synonyms: 2,6-DICHLORO-N-HYDROXYBENZENECARBOXIMIDOYL CHLORIDE;ALPHA,2,6-TRICHLOROBENZALDOXIME, TECH.;2,6-DICHLORO-N-HYDROXYBENZENECARBOXIMIDOYL CHLOR;2,6-Dichloro-n-hydroxybenzenecarboximidoyl chlorid;2,6-Dichloro-N-hydroxybenzenecarboximidoyl chloride , Tech.;alpha-Chloro-2,6-dichlorobenzaldoxime;2,6-Dichlorobenzenehydroximic acid chloride;2,6-Dichlorobenzohydroxamoyl chloride
• CAS NO: 6579-27-7
• Molecular Formula: C₇H₄Cl₃NO
• Molecular Weight: 224.47
• Mol File: 6579-27-7.mol

Chemical Properties

• Melting Point: 85 °C
• Boiling Point: 349.187 °C at 760 mmHg
• Flash Point: 164.983 °C
• Appearance: /
• Density: 1.53
• Vapor Pressure: 1.79E-05mmHg at 25°C
• Refractive Index: 1.597
• PKA: 9.77±0.70(Predicted)
• CAS DataBase Reference: 2,6-DICHLORO-N-HYDROXYBENZENECARBOXIMIDOYL CHLORIDE(CAS DataBase Reference)
• NIST Chemistry Reference: 2,6-DICHLORO-N-HYDROXYBENZENECARBOXIMIDOYL CHLORIDE(6579-27-7)
• EPA Substance Registry System: 2,6-DICHLORO-N-HYDROXYBENZENECARBOXIMIDOYL CHLORIDE(6579-27-7)

Safety Data

• Hazard Codes: C
• Hazardous Substances Data: 6579-27-7(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
2,6-Dichloro-n-hydroxybenzenecarboximidoyl chloride is used as a chemical intermediate for the synthesis of various pharmaceuticals. Its unique structure allows it to be a key component in the development of new drugs and medications.
Used in Dye and Pigment Industry:
2,6-Dichloro-n-hydroxybenzenecarboximidoyl chloride is used as an intermediate in the production of dyes and pigments. Its chemical properties contribute to the color and stability of these products, making it an essential component in this industry.
Used in Specialty Chemicals Manufacturing:
2,6-Dichloro-n-hydroxybenzenecarboximidoyl chloride is also used in the manufacture of some specialty chemicals. Its versatility and reactivity make it a valuable building block for creating unique and specialized chemical products.
Safety Precautions:
It is important to handle 2,6-Dichloro-n-hydroxybenzenecarboximidoyl chloride with caution, as it can be harmful if swallowed, inhaled, or absorbed through the skin. It may cause irritation to the respiratory system, skin, and eyes. Proper safety measures, such as wearing protective gear and working in a well-ventilated area, should be taken to minimize potential risks.

InChI:InChI=1/C7H4Cl3NO/c8-4-2-1-3-5(9)6(4)7(10)11-12/h1-3,12H

Upstream product

• 6575-28-6 (1E)-2,6-dichlorobenzaldehyde oxime 
• 3714-77-0 2,6-dichlorobenzaldoxime 
• 25185-95-9 2,6-dichlorobenzaldoxime 
• 83-38-5 2,6-dichlorobenzaldehyde 

Downstream Products

• 135073-84-6 3-(2,6-Dichloro-phenyl)-5,7-dimethyl-7,7a-dihydro-3aH-isoxazolo[5,4-d]pyrimidine-4,6-dione 
• 135073-83-5 1,3-Dimethyl-5-(2,6-dichlorobenzoyl)uracil oxime 
• 144104-79-0 1,3-dimethyl-5-(2,6-dichlorobenzoyl)-6-methyluracil oxime 
• 144104-80-3 3-(2,6-dichlorophenyl)-5,7,8-trimethyl-8,9-dihydroisoxazolo<5,4-d>pyrimidine-4,6(5H,7H)-dione 
• 144104-82-5 5-(2,6-Dichloro-phenyl)-1H-pyrimido[5,4-d][1,2]oxazine-2,4,8-trione 
• 135073-79-9 5-(2,6-Dichlorobenzoyl)-2'-deoxyuridine oxime 
• 135073-77-7 5-(2,6-Dichlorobenzoyl)-2',3',5'-tri-O-benzoyluridine oxime 
• 4402-83-9 SPB 06193 
• 933800-10-3 methyl 5-tert-butyl-3-(2,6-dichlorophenyl)isoxazole-4-carboxylate 
• 933800-08-9 methyl 5-biphenyl-4-yl-3-(2,6-dichlorophenyl)isoxazole-4-carboxylate 
• 933800-01-2 methyl 3-(2,6-dichlorophenyl)-5-naphthalen-2-ylisoxazole-4-carboxylate 
• 1190283-72-7 C₁₅H₁₅Cl₂NO₄ 
• 1190283-77-2 C₁₆H₁₇Cl₂NO₄ 

Relevant articles and documents

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.

BENZISOXAZOLE COMPOUND

The present invention provides a compound, a salt thereof, or a prodrug thereof as a compound effective for preventing and/or treating fibrosis, the compound being represented by formula (1) (wherein A is an optionally substituted benzene ring; B is optionally substituted aryl or optionally substituted heteroaryl; X is an oxygen atom or a sulfur atom; Y is a nitrogen atom or a carbon atom; ------ of -----Y is a single or double bond when Y is a carbon atom, or ------ of -----Y is a single bond when Y is a nitrogen atom; each R1 independently represents lower alkyl, or two R1s may be bound to each other to form a spiro ring or a crosslinked structure, or two R1s may be bound to each other to form a saturated fused heterocycle together with nitrogen and carbon atoms constituting a ring containing Y; p is 0, 1, or 2; or (R1)p is oxo) .

PPARs-FXR multi-target micromolecular agonist as well as preparation method and application thereof

The invention discloses a PPARs-FXR multi-target micromolecule agonist and a preparation method and application thereof, the structure is shown in a general formula I, and the definition of each substituent group is shown in the description and claims. Th

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.

Discovery of a novel and orally active Farnesoid X receptor agonist for the protection of acetaminophen-induced hepatotoxicity

Acetaminophen (APAP) overdose is a leading cause of acute hepatic failure and liver transplantation, while the existing treatments are poorly effective. Therefore, it is necessary to develop effective therapeutic drugs for APAP-induced hepatotoxicity. Farnesoid X receptor (FXR) is a potential target for the treatment of liver disease, and the activation of FXR protects mice against APAP-induced hepatotoxicity. Compound 5, a glycine-conjugated derivative of FXR agonist 4, was designed to extend the chemical space of existing FXR agonists. Molecular modeling study indicated that compound 5 formed hydrogen bond network with key residues of FXR. Moreover, compound 5 (10?mg/kg) revealed better protective effects against APAP-induced hepatotoxicity than parent compound 4 (30?mg/kg). Further mechanical research indicated that compound 5 regulated the expressions of genes related to FXR and oxidative stress. These findings suggest that compound 5 is a promising FXR agonist suitable for further research, and it is the first time to verify that the glycine-conjugated derivative five exerted better protective effects than its parent compound.

Dual Farnesoid X Receptor/Soluble Epoxide Hydrolase Modulators Derived from Zafirlukast

The nuclear farnesoid X receptor (FXR) and the enzyme soluble epoxide hydrolase (sEH) are validated molecular targets to treat metabolic disorders such as non-alcoholic steatohepatitis (NASH). Their simultaneous modulation in vivo has demonstrated a triad of anti-NASH effects and thus may generate synergistic efficacy. Here we report dual FXR activators/sEH inhibitors derived from the anti-asthma drug Zafirlukast. Systematic structural optimization of the scaffold has produced favorable dual potency on FXR and sEH while depleting the original cysteinyl leukotriene receptor antagonism of the lead drug. The resulting polypharmacological activity profile holds promise in the treatment of liver-related metabolic diseases.

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.

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.

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).

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.