46503-52-0

Usage

Uses

Used in Pharmaceutical Industry:
1-(2,4-DICHLOROPHENYL)-2-(1H-IMIDAZOLE-1-YL) ETHANONE is used as a key intermediate for the synthesis of antifungal, antibacterial, and anti-inflammatory drugs. Its unique chemical structure allows for the development of new chemical entities with therapeutic applications, enhancing the range of treatments available for various medical conditions.
Used in Agrochemical Industry:
This chemical is also utilized in the development of new pesticides, contributing to the advancement of crop protection strategies and ensuring food security by combating pests and diseases in agriculture.
Used in Industrial Applications:
1-(2,4-DICHLOROPHENYL)-2-(1H-IMIDAZOLE-1-YL) ETHANONE may have potential uses in other industrial applications, although specific details are not provided in the materials. Its versatility as a chemical intermediate suggests that it could be employed in the creation of various products across different sectors.

Upstream product

• 288-32-4 1H-imidazole 
• 4252-78-2 2,2',4'-trichloroacetophenone 
• 2631-72-3 2,4-dichlorophenacyl bromide 
• 78344-77-1 2-diazo-1-(2,4-dichlorophenyl)ethanone 
• 7732-18-5 water 
• 2234-16-4 1-(2,4-dichlorophenyl)ethan-1-one 
• 541-73-1 1,3-Dichlorobenzene 

Downstream Products

• 104061-06-5 1-[2-(2,4-dichlorophenyl)-2-(4-phenyl-piperazine)vinyl]-1H-imidazole 
• 78202-17-2 2-(2,4-dichlorophenyl)-1-(1-imidazolyl)-pentan-2-ol 
• 78202-15-0 2-(2,4-dichlorophenyl)-1-(1-imidazolyl)-pent-4-en-2-ol 
• 100220-48-2 (Z)-1-(2,4-Dichlorophenyl)-2-(1H-imidazol-1-yl)ethanone oxime 
• 27646-28-2 (S)-1-(2,4-dichlorophenyl)-2-(1H-imidazol-1-yl)ethan-1-ol 
• 27656-21-9 (R)-1-(2,4-dichlorophenyl)-2-(1H-imidazol-1-yl)ethanol 
• 94038-16-1 1-(2,4-dichlorophenyl)-2-(1H-imidazole-1-yl)ethylamine 
• 94038-18-3 (±)-1-(2-azido-2-(2, 4-dichlorophenyl)ethyl)-1H-imidazole 

Relevant academic research and scientific papers

Lead optimization generates selenium-containing miconazole CYP51 inhibitors with improved pharmacological profile for the treatment of fungal infections

A series of selenium-containing miconazole derivatives were identified as potent antifungal drugs in our previous study. Representative compound A03 (MIC = 0.01 μg/mL against C.alb. 5314) proved efficacious in inhibiting the growth of fungal pathogens. However, further study showed lead compound A03 exhibited potential hemolysis, significant cytotoxic effect and unfavorable metabolic stability and was therefore modified to overcome these drawbacks. In this article, the further optimization of selenium-containing miconazole derivatives resulted in the discovery of similarly potent compound B17 (MIC = 0.02 μg/mL against C.alb. 5314), exhibiting a superior pharmacological profile with decreased rate of metabolism, cytotoxic effect and hemolysis. Furthermore, compound B17 showed fungicidal activity against Candida albicans and significant effects on the treatment of resistant Candida albicans infections. Meanwhile, compound B17 not only could reduce the ergosterol biosynthesis pathway by inhibiting CYP51, but also inhibited biofilm formation. More importantly, compound B17 also shows promising in vivo efficacy after intraperitoneal injection and the PK study of compound B17 was evaluated. In addition, molecular docking studies provide a model for the interaction between the compound B17 and the CYP51 protein. Overall, we believe that these selenium-containing miconazole compounds can be further developed for the potential treatment of fungal infections.

BuChE-IDO1 inhibitor as well as preparation method and application thereof

The invention relates to the field of medicines, and particularly discloses a BuChE-IDO1 inhibitor as well as a preparation method and application thereof. The 7-chlorine-3-substituted benzothiophene part of sertaconazole is chemically modified, the influence of the 7-chlorine-3-substituted benzothiophene part of sertaconazole on the in-vitro inhibitory activity of AChE, BuChE and IDO1 is explored, the target compound is further optimized, and the technical problems that an existing BuChE-IDO1 inhibitor is poor in pertinence and safety are solved. What is explored is that an appropriate substituent group introduced to a 2-benzothiazole ring can form additional interaction with surrounding amino acids and heme iron, so that the binding affinity of the analogue with BuChE and IDO1 is increased, and a new idea is broadened for more efficient and targeted treatment of advanced AD diseases.

Novel BuChE-IDO1 inhibitors from sertaconazole: Virtual screening, chemical optimization and molecular modeling studies

In our effort towards the identification of novel BuChE-IDO1 dual-targeted inhibitor for the treatment of Alzheimer's disease (AD), sertaconazole was identified through a combination of structure-based virtual screening followed by MM-GBSA rescoring. Preliminary chemical optimization was performed to develop more potent and selective sertaconazole analogues. In consideration of the selectivity and the inhibitory activity against target proteins, compounds 5c and 5d were selected for the next study. Further modification of compound 5c led to the generation of compound 10g with notably improved selectivity towards BuChE versus AChE. The present study provided us with a good starting point to further design potent and selective BuChE-IDO1 inhibitors, which may benefit the treatment of late stage AD.

One pot synthesis of α-N-heteroaryl ketone derivatives from aryl ketones using aqueous NaICl2

A simple and efficient method for the synthesis of α-heteroaryl ketones from aryl ketones and amine using aqueous sodium dichloroiodate is established. This method is mild, operationally simple, has a short reaction time, and easy workup procedure to afford the corresponding α-N-heteroaryl ketone derivatives in moderate to good yield.

Inhibition of hedgehog signaling by stereochemically defined des-triazole itraconazole analogues

Dysregulation of the hedgehog (Hh) signaling pathway is associated with cancer occurrence and development in various malignancies. Previous structure-activity relationships (SAR) studies have provided potent Itraconazole (ITZ) analogues as Hh pathway antagonists. To further expand on our SAR for the ITZ scaffold, we synthesized and evaluated a series of compounds focused on replacing the triazole. Our results demonstrate that the triazole region is amenable to modification to a variety of different moieties; with a single methyl group representing the most favorable substituent. In addition, nonpolar substituents were more active than polar substituents. These SAR results provide valuable insight into the continued exploration of ITZ analogues as Hh pathway antagonists.

Design, synthesis, and biological evaluation of novel miconazole analogues containing selenium as potent antifungal agents

Herein, based on the theory of bioisosterism, a series of novel miconazole analogues containing selenium were designed, synthesized and their inhibitory effects on thirteen strains of pathogenic fungi were evaluated. It is especially encouraging that all the novel target compounds displayed significant antifungal activities against all tested strains. Furthermore, all the target compounds showed excellent inhibitory effects on fluconazole-resistant fungi. Subsequently, preliminary mechanistic studies indicated that the representative compound A03 had a strong inhibitory effect on C.alb. CYP51. Moreover, the target compounds could prevent the formation of fungi biofilms. Further hemolysis test verified that potential compounds had higher safety than miconazole. In addition, molecular docking study provided the interaction modes between the target compounds and C.alb. CYP51. These results strongly suggested that some target compounds are promising as novel antifungal drugs.

Design and Synthesis of Tetrazole- And Pyridine-Containing Itraconazole Analogs as Potent Angiogenesis Inhibitors

Itraconazole, a widely used antifungal drug, was found to possess antiangiogenic activity and is currently undergoing multiple clinical trials for the treatment of different types of cancer. However, it suffers from extremely low solubility and strong interactions with many drugs through inhibition of CYP3A4, limiting its potential as a new antiangiogenic and anticancer drug. To address these issues, a series of analogs in which the phenyl group is replaced with pyridine or fluorine-substituted benzene was synthesized. Among them the pyridine- and tetrazole-containing compound 24 has significantly improved solubility and reduced CYP3A4 inhibition compared to itraconazole. Similar to itraconazole, compound 24 inhibited the AMPK/mTOR signaling axis and the glycosylation of VEGFR2. It also induced cholesterol accumulation in the endolysosome and demonstrated binding to the sterol-sensing domain of NPC1 in a simulation study. These results suggested that compound 24 may serve as an attractive candidate for the development of a new generation of antiangiogenic drug.

Antifungal activity, mode of action variability, and subcellular distribution of coumarin-based antifungal azoles

Azole antifungals inhibit the biosynthesis of ergosterol, the fungal equivalent of cholesterol in mammalian cells. Here we report an investigation of the activity of coumarin-substituted azole antifungals. Screening against a panel of Candida pathogens, including a mutant lacking CYP51, the target of antifungal azoles, revealed that this enzyme is inhibited by triazole-based antifungals, whereas imidazole-based derivatives have more than one mode of action. The imidazole-bearing antifungals more effectively reduced trailing growth associated with persistence and/or recurrence of fungal infections than triazole-based derivatives. The imidazole derivatives were more toxic to mammalian cells and more potently inhibited the activity of CYP3A4, which is one of the main causes of azole toxicity. Using live cell imaging, we showed that regardless of the type of azole ring fluorescent 7-diethylaminocoumarin-based azoles localized to the endoplasmic reticulum, the organelle that harbors CYP51. This study suggests that the coumarin is a promising scaffold for development of novel azole-based antifungals that effectively localize to the fungal cell endoplasmic reticulum.

Anti-staphylococcal biofilm activity of miconazoctylium bromide

We designed and synthesized miconazole analogues containing a substituted imidazolium moiety. The structural modification of the miconazole led to a compound with high potency to prevent the formation and disrupt bacterial biofilms, as a result of accumulation in the biofilm matrix, permeabilization of the bacterial membrane and generation of reactive oxygen species in the cytoplasm.

Preparation method of ketoconazole

The invention belongs to the technical field of medicine synthesis and in particular relates to a preparation method of ketoconazole. The preparation method of the ketoconazole, provided by the invention, comprises the following step: S101: enabling a compound shown as a formula I and a compound shown as a formula II to be mixed for reaction in an acidic medium to obtain the ketoconazole. According to the preparation method of the ketoconazole, the steric hindrance of the compound shown as the formula I and the compound shown as the formula II is great, so that the cis-trans selectivity of 1,3-dioxolame formed by reaction of the compound shown as the formula I and the compound shown as the formula II is remarkably improved, and furthermore, a benzoyl removing step is omitted; finally, theproduction period of the ketoconazole is shortened and the cost is reduced; meanwhile, the utilization of dangerous substances including bromine liquid and the like is reduced; the technical defects in the prior art that steps for synthesizing the ketoconazole is more and the yield and the purity are low are overcome.