134071-11-7

Usage

Uses

Used in Pharmaceutical Industry:
1-(2,4-DIFLUOROPHENYL)-2-(1H-IMIDAZOL-1-YL)-1-ETHANONE is used as a topical medication for the treatment of skin conditions such as eczema, dermatitis, and psoriasis. It works by reducing inflammation and suppressing the immune response in the skin, providing relief from itching, redness, and swelling associated with these conditions.
Used in Dermatology:
1-(2,4-DIFLUOROPHENYL)-2-(1H-IMIDAZOL-1-YL)-1-ETHANONE is used as a therapeutic agent in dermatology for managing skin inflammation and allergic reactions. Its anti-inflammatory and immunosuppressive effects help alleviate symptoms and promote healing of the affected skin areas.

InChI:InChI=1/C11H8F2N2O/c12-8-1-2-9(10(13)5-8)11(16)6-15-4-3-14-7-15/h1-5,7H,6H2

Upstream product

• 288-32-4 1H-imidazole 
• 51336-94-8 2-chloro-1-(2,4-dichlorophenyl)ethanone 
• 102429-07-2 2-bromo-2',4'-difluoroacetophenone 
• 364-83-0 2',4'-difluoroacetophenone 
• 372-18-9 1,3-Difluorobenzene 

Downstream Products

• 477948-96-2 1-(2,4-difluorophenyl)-2-(1H-imidazol-1-yl)ethan-1-ol 

Relevant academic research and scientific papers

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.

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.

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.

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.

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.

Diaryl-containing imidazole compound and preparation method and medical application thereof

The invention discloses a diaryl-containing imidazole compound. The invention further discloses application of the diaryl-containing imidazole compound to preparation of drugs for preventing or treating Alzheimer's disease. The inventor screens butyrylcholine esterase and IDO1 as carriers for inhibiting the activity to evaluate the effect of the diaryl imidazole compound to treat Alzheimer's disease, and finds that the diaryl imidazole compound has good in vitro activity, and can be further developed as a precursor substance for performing the Alzheimer's disease resistant effect by inhibitingthe activity of cholinesterase. (The formula is shown in the description).

Substituted imidazole-1-vinyl compound and use thereof

The invention relates to a substituted imidazole-1-ethylene compound as well as a preparation and an application thereof. The substituted imidazole-1-ethylene compound is a compound shown as a formula I, or salts thereof formed with medicinal acids or bases. According to the antifungal activity test performed on eight clinical fungi by the compound provided in the invention, a good fungus killing effect is achieved. The compound can serve as a novel broad-spectrum antifungal activity compound and is developed into antifungal medicines, disinfectants or feed additives.

A short synthesis of 3,6-disubstituted N-2-thienyl/aryl-indoles

A short synthetic strategy for 3,6-disubstituted-N-2-thienyl/aryl-indoles, involving reaction of substituted 2,4-difluoro/dichloro-styrene epoxide with substituted 2-formylaminothiophenes or substituted N-formylanilines in the presence of a base followed by treatment with an acid, has been developed. The method was applied for the synthesis of a number of indoles with a variety of substituents at 1, 3, and 6 positions of the indole moiety.

Novel azole or triazole derivatives, method for preparing the same and use thereof as antifungal medicaments

The invention concerns novel azole or triazole derivatives of formula (I), wherein: X, Ar1, Ar3, A, R1, R5, R6, R7 and B are such as defined in the description, their preparation method and their use as antifungal medicines.

Antifungal 4-[4-[4-[4-[[2-(2,4-difluorophenyl)-2-(1H-azolylmethyl)-1,3-dioxolan-4-yl]methoxy]phenyl]-1-piperazinyl]phenyl]triazolones and imidazolones

4-[4-[4-[4-[[2-(2,4-difluorophenyl)-2-(1H-azolylmethyl)-1,3-dioxolan-4-yl]methoxy]phenyl]-1-piperazinyl]phenyl]triazolones and imidazolones, their pharmaceutically acceptable acid addition salts and stereoisomeric forms having improved antifungal properti