3024-72-4

Usage

Uses

Used in Pharmaceutical Industry:
3,4-Dichlorobenzoyl chloride is used as a key intermediate in the synthesis of 3,4-dichlorophenylacetic acid, which is an important compound in the production of various pharmaceuticals. Its role in the synthesis process is crucial for the development of drugs that target specific medical conditions.
Used in Chemical Synthesis:
3,4-Dichlorobenzoyl chloride is also used as a reagent in various chemical synthesis processes. Its unique chemical properties make it a valuable component in the creation of different chemical compounds, contributing to the advancement of the chemical industry.

InChI:InChI=1/C8H5Cl3O/c9-6-2-1-5(3-7(6)10)4-8(11)12/h1-3H,4H2

Upstream product

• 51-44-5 3,4-dichlorbenzoic acid 
• 13014-24-9 3,4-dichloro-1-trichloromethylbenzene 

Downstream Products

• 109554-80-5 3,4-dichloro-benzoic acid-(1-phenyl-2-pyrrolidino-ethyl ester); hydrochloride 
• 2448-04-6 3,4-dichloro-benzoic acid-(4-chloro-anilide) 
• 35455-59-5 5,3',4'-trichloro-2-hydroxy-benzophenone 
• 7506-97-0 3,4-dichloro-N,N-diethylbenzamide 
• 133231-79-5 3,4-dichloro-benzoic acid-(2-diethylamino-ethylamide); hydrochloride 
• 28394-59-4 3,4-dichloro-benzoic acid-(2,2,2-trichloro-ethyl ester) 
• 5452-18-6 3,4-dichloro-benzoic acid-(2-amino-4-oxo-3,4,5,6,7,8-hexahydro-quinazolin-6-ylamide) 
• 106522-45-6 N,N'-bis-(3,4-dichloro-benzoyl)-urea 
• 7501-10-2 3,4-dichloro-benzoic acid-(2-chloro-ethyl ester) 
• 2670-38-4 3,4-dichlorobenzamide 
• 25962-22-5 4-[(R)-2-(3,4-dichloro-benzoyloxy)-2-((1S)-3c,5t-dimethyl-2-oxo-cyclohex-r-yl)-ethyl]-piperidine-2,6-dione 
• 33764-00-0 (3,4-dichlorophenyl)(morpholin-4-yl)methanone 
• 34333-43-2 4-(3,4-dichloro-benzoyl)-2,6-dimethyl-morpholine 
• 50350-38-4 3,4-dichloro-N-thiazol-2-yl-benzamide 

Relevant academic research and scientific papers

Discovery and Mechanism of Action of Small Molecule Inhibitors of Ceramidases**

Sphingolipid metabolism is tightly controlled by enzymes to regulate essential processes in human physiology. The central metabolite is ceramide, a pro-apoptotic lipid catabolized by ceramidase enzymes to produce pro-proliferative sphingosine-1-phosphate. Alkaline ceramidases are transmembrane enzymes that recently attracted attention for drug development in fatty liver diseases. However, due to their hydrophobic nature, no specific small molecule inhibitors have been reported. We present the discovery and mechanism of action of the first drug-like inhibitors of alkaline ceramidase 3 (ACER3). In particular, we chemically engineered novel fluorescent ceramide substrates enabling screening of large compound libraries and characterized enzyme:inhibitor interactions using mass spectrometry and MD simulations. In addition to revealing a new paradigm for inhibition of lipid metabolising enzymes with non-lipidic small molecules, our data lay the ground for targeting ACER3 in drug discovery efforts.

Structure-Activity Study of Nitazoxanide Derivatives as Novel STAT3 Pathway Inhibitors

We identified nitazoxanide (NTZ) as a moderate STAT3 pathway inhibitor through immunoblot analysis and a cell-based IL-6/JAK/STAT3 pathway activation assay. A series of thiazolide derivatives were designed and synthesized to further validate the thiazolide scaffold as STAT3 inhibitors. Eight out of 25 derivatives displayed potencies greater than that of NTZ, and their STAT3 pathway inhibitory activities were found to be significantly correlated with their antiproliferative activities in HeLa cells. Derivatives 15 and 24 were observed to be more potent than the positive control WP1066, which is under phase I clinical trials. Compared with NTZ, 15 also exhibited much improved in vivo pharmacokinetic parameters in rats and efficacies against proliferations in multiple cancer cell lines, indicating a broad-spectrum effect of these thiazolides as antitumor agents targeted on STAT3.

Benzoyl-containing rupestonic acid methyl ester derivative as well as preparation method and application thereof

The invention relates to a benzoyl-containing rupestonic acid methyl ester derivative as well as a preparation method and application thereof. Rupestonic acid and dimethyl sulfate react to obtain rupestonic acid methyl ester, 2-hydroxyl rupestonic acid methyl ester is prepared under oxidation of camphor sulfonyl acridine, and then the 2-hydroxyl rupestonic acid methyl ester reacts with different substituted benzoyl chloride under the catalysis of DMAP to obtain the 1d-15d benzoyl-containing rupestonic acid methyl ester derivative. The method has the advantages of mild reaction conditions and simple experimental steps. The obtained benzoyl-containing rupestonic acid methyl ester derivative 1d-15d is subjected to an anti-H3N2 influenza A virus activity test in 1d-15d. Experimental results show that the compounds 1d, 2d, 4d, 5d, 7d, 8d, 12d, 13d and 15d can be applied to preparation of drugs for resisting influenza A H3N2 virus.

Synthesis and structure-activity relationship studies of n-monosubstituted aroylthioureas as urease inhibitors

Background: Thiourea is a classical urease inhibitor which is usually used as a positive control, and many N,N'-disubstituted thioureas have been determined as urease inhibitors. However, due to steric hindrance, N,N'-disubstituted thiourea motif could not bind urease as thiourea. On the contrary, N-monosubstituted thiourea with a tiny thiourea motif could theoretically bind into the active pocket as thiourea. Objective: A series of N-monosubstituted aroylthioureas were designed and synthesized for evaluation as urease inhibitors. Methods: Urease inhibition was determined by the indophenol method and IC50 values were calculated using computerized linear regression analysis of quantal log dose-probit functions. The kinetic parameters were estimated via surface plasmon resonance (SPR) and by nonlinear regression analysis based on the mixed type inhibition model derived from Michaelis-Menten kinetics. Results: Compounds b2, b11, and b19 reversibly inhibited urease with a mixed mechanism, and showed excellent potency against both cell-free urease and urease in the intact cell, with IC50 values being 90-to 450-fold and 5-to 50-fold lower than the positive control acetohydroxamic acid, respectively. The most potent compound b11 showed an IC50 value of 0.060 ± 0.004μM against cell-free urease, which bound to urea binding site with a very low KD value (0.420±0.003nM) and a very long residence time (6.7 min). Compound b11 was also demonstrated to have very low cytotoxicity to mammalian cells. Conclusion: The results revealed that N-monosubstituted aroylthioureas bound to the active site of urease as expected, and represent a new class of urease inhibitors for the development of potential therapeutics against infections caused by urease-containing pathogens.

Preparation method of benzoyl chloride compound

The invention provides a preparation method of a benzoyl chloride compound. The preparation method comprises the following step: with a trichloromethyl benzene compound and a benzoic acid compound as raw materials and ferric oxide as a catalyst, carrying out a catalytic reaction to prepare the benzoyl chloride compound. According to the method disclosed by the invention, the benzoyl chloride compound can be obtained under the condition of not using a solvent, yield is up to 95% or above, atom economy is good, cost is lower, operation is simpler, more convenient and safer, the treatment amount of three wastes is smaller, the three wastes is easier to treat, and the method is more suitable for industrial production.

Discovery of methoxy-naphthyl linked N-(1-benzylpiperidine) benzamide as a blood-brain permeable dual inhibitor of acetylcholinesterase and butyrylcholinesterase

The cholinesterase enzymes play a vital role in maintaining balanced levels of the neurotransmitter acetylcholine in the central nervous system. However, the overexpression of these enzymes results in hampered neurotransmission. Both the major forms of cholinesterase enzymes viz. acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) play a crucial role in blocking neurotransmission; therefore, in recent years, a strategy of dual cholinesterase inhibition is being explored. Herein, we developed an energy-optimized e-pharmacophore hypothesis AHHPRR from AChE-donepezil complex and screened a set of 15 scaffolds that were designed imaginarily. The ligand with N-(1-benzylpyridinium) benzamide framework has shown the highest fitness and volume score, which was chosen for synthesis and validation. A series of pyridinium benzamides were synthesized and screened for cholinesterase inhibition that led to the identification of 7b, a naphthalene containing N-(1-benzylpiperidine) benzamide as a potent dual AChE and BChE inhibitor with IC50 values of 0.176, and 0.47 μM, respectively. The kinetic study indicated that 7b inhibits AChE in a non-competitive manner with Ki value of 0.21 μM, and BChE in a mixed-fashion with Ki of 0.15 μM. The observed mode of inhibition was corroborated with molecular docking studies. The MD simulation studies pointed out that both AChE and BChE undergo low conformational changes in complex with 7b. The benzamide 7b displayed high BBB permeability in PAMPA assay, which indicates its potential for further exploration in preclinical studies for Alzheimer's disease.

GLYCOLATE OXIDASE INHIBITORS FOR THE TREATMENT OF DISEASE

Described herein are compounds, methods of making such compounds, pharmaceutical compositions and medicaments containing such compounds, and methods of using such compounds to treat or prevent diseases or disorders associated with a defect in glyoxylate metabolism, for example a disease or disorder associated with the enzyme glycolate oxidase (GO) or alterations in oxalate metabolism. Such diseases or disorders include, for example, disorders of glyoxylate metabolism, including primary hyperoxaluria, that are associated with production of excessive amounts of oxalate.

Light-Switchable Antagonists for the Histamine H1 Receptor at the Isolated Guinea Pig Ileum

The histamine H1 G protein-coupled receptor (GPCR) plays an important role in allergy and inflammation. Existing drugs that address the H1 receptor differ in their chemical structure, pharmacology, and side effects. Light-controllable spatial and temporal activity regulation of photochromic H1 ligands may contribute to a better mechanistic understanding and the development of improved correlations between ligand structure and pharmacologic effects. We report photochromic H1 receptor ligands, which were investigated in an organ-pharmacological assay. Initially, five photochromic azobenzene derivatives of reported dual H1–H4 receptor antagonists were designed, synthesized, photochemically characterized, and organ-pharmacologically tested on the isolated guinea pig ileum. Among them, one compound [trans-19: (Z)-1-(4-chlorophenyl)-1-(4-methylpiperazin-1-yl)-N-(4-((E)-phenyldiazenyl)phenyl)methanimine] retained the antagonistic activity of its non-photochromic lead, and trans–cis isomerization by irradiation induced a fourfold difference in the pharmacological response. Further structural optimization resulted in two bathochromically shifted derivatives of 19 [NO2-substituted 35 {(Z)-1-(4-chlorophenyl)-1-(4-methylpiperazin-1-yl)-N-(4-((E)-(4-nitrophenyl)diazenyl)phenyl)methanimine} and SO3?-substituted 41 {4-((E)-(4-(((Z)-(4-chlorophenyl)(4-methylpiperazin-1-yl)methylene)amino)phenyl)diazenyl)benzenesulfonate}], which do not require the use of UV light for photoisomerization and which also have improved solubility and show reduced tissue impairment. The trans isomers of both compounds showed a remarkable increase in antagonistic activity relative to their lead trans-19; furthermore, a 46-fold difference in activity on the isolated guinea pig ileum was observed between trans- and cis-35.

GLYCOLATE OXIDASE INHIBITORS FOR THE TREATMENT OF DISEASE

Described herein are compounds, methods of making such compounds, pharmaceutical compositions and medicaments containing such compounds, and methods of using such compounds to treat or prevent diseases or disorders associated with the enzyme glycolate oxidase (GO). Such diseases or disorders include, for example, disorders of glyoxylate metabolism, including primary hyperoxaluria, that are associated with production of excessive amounts of oxalate.

Design and synthesis of 3-aminophthalazine derivatives and structural analogues as PDE5 inhibitors: anti-allodynic effect against neuropathic pain in a mouse model

Neuropathic pain is a chronic pain caused by a lesion or disease affecting the somatosensory nervous system. To date, no specific treatment has been developed to cure this pain. Antidepressants and anticonvulsant drugs are used, but they do not demonstrate universal efficacy, and they often cause detrimental adverse effects. Some studies highlighted the efficacy of sildenafil, a well-known inhibitor of phosphodiesterase 5 (PDE5, (IC50 = 3.3 nM)), in models of pain. Based on these results, we focused our attention on MY 5445, another known PDE5 inhibitor. Homologues, isosteres and structural analogues of MY 5445 were designed and all synthesized compounds were evaluated for their inhibitory activity toward PDE5. Selectivity profiles towards other PDE1-4 isoenzymes, water solubility and stability in acidic medium of the most potent PDE5 inhibitors were determined and the aminophthalazine 16h and its mimetic 41n (3-aminoindazole)were evaluated in comparison to MY 5445 (4b)in vivo in a model of neuropathic pain induced by sciatic nerve cuffing in mice (3 and 0.5 mg/kg, ip twice a day). Both compounds showed the same efficacy on neuropathic allodynia as MY 5445, and thus produced a significant relief of mechanical hypersensitivity after 12 days of treatment.