51336-94-8

Usage

Uses

Used in Pharmaceutical Applications:
2-Chloro-2',4'-difluoroacetophenone is used as an inhibitor for protein tyrosine phosphatases SHP-1 and PTP1B. These phosphatases play a crucial role in various cellular processes, and their inhibition can have significant implications in the development of therapeutic strategies for various diseases.
Used in Chemical Synthesis:
In the chemical industry, 2-Chloro-2',4'-difluoroacetophenone is utilized in the synthesis of allyl alcohol. This versatile compound serves as a building block for the creation of various organic compounds and materials, contributing to the development of new products and technologies.
Used in Research and Development:
Due to its unique chemical properties, 2-Chloro-2',4'-difluoroacetophenone is also employed in research and development settings. It is used to study the interactions and effects of α-haloacetophenone derivatives on protein tyrosine phosphatases, which can lead to a better understanding of their role in cellular processes and potential applications in medicine.

Upstream product

• 1440-61-5 N-chloroacetylmorpholine 
• 348-57-2 2,4-difluorobromobenzene 
• 79-11-8 chloroacetic acid 
• 106614-28-2 methyl 2,4-difluorobenzoate 
• 364-83-0 2',4'-difluoroacetophenone 
• 372-18-9 1,3-Difluorobenzene 
• 78-95-5 chloroacetone 
• 79-04-9 chloroacetyl chloride 

Downstream Products

• 122263-03-0 2-Acetyloxy-1-(2,4-difluorophenyl)ethanone 
• 129793-24-4 2-(2,4-Difluorophenyl)-2-(1-[pyridin-2-yl]ethyl)oxirane 
• 1026500-07-1 4-{5-[2-Chloro-1-(2,4-difluoro-phenyl)-1-hydroxy-ethyl]-thiazol-2-yl}-benzonitrile 
• 1025877-72-8 2-Chloro-1-(2,4-difluoro-phenyl)-1-[4-(2,4-difluoro-phenyl)-thiazol-2-yl]-ethanol 
• 308368-72-1 [2-(4-{4-[4-(2,4-difluoro-phenyl)-thiazol-2-yl]-benzenesulfonylamino}-phenyl)-ethyl]-(2-hydroxy-2-pyridin-3-yl-ethyl)-carbamic acid tert-butyl ester 
• 330156-49-5 (S)-2-chloro-1-(2’,4’-difluorophenyl)ethanol 
• 234759-78-5 2-(cyclopropylthio)-2',4'-difluoroacetophenone 
• 192862-10-5 2',4'-difluoro-α-(methylthio)acetophenone 
• 86404-63-9 1-(2,4-difluorophenyl)-2-(1H-1,2,4-triazolyl)ethanone 
• 185302-85-6 methyl 3-(2,4-difluorophenyl)-3-oxopropanoate 

Relevant academic research and scientific papers

Discovery of potential antifungal triazoles: Design, synthesis, biological evaluation, and preliminary antifungal mechanism exploration

A series of triazoles as miconazole analogues was designed, synthesized and characterized by IR, NMR, MS and HRMS. All the newly prepared compounds were screened for their antifungal activities against five kinds of fungi. The bioactive assay showed that most of the synthesized compounds exhibited good or even stronger antifungal activities in comparison with the reference drugs miconazole and fluconazole. In particular, the 3,4-dichlorobenzyl derivative 5b showed a comparable or superior activity against all the tested fungal strains to standard drugs, and formed a supramolecular complex with CYP51 via the hydrogen bond between the 4-nitrogen of the triazole nucleus and the histidine residue. Preliminary experiments revealed that both of the active molecules 5b and 9c could intercalate into calf thymus DNAs, which might block DNA replication to exhibit their powerful antifungal abilities. Further studies indicated that compound 5b might be stored and transported by human serum albumin through hydrophobic interactions, specific electrostatic interactions and hydrogen bonds. These results strongly suggested that compound 5b could serve as a promising antifungal candidate.

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.

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.

Antibacterial drug and preparation method thereof

The invention discloses an antibacterial drug. The antibacterial drug is 2-(2,4-difluorophenyl)-1-(1H-1,2,4-triazol-1-yl)-3-(1H-1,2,3,4-tetrazol-1-yl)-2-propanol, the compound is obtained by modifyingfluconazole and introducing a tetrazole ring. Compared with fluconazole, the compound has wider antimicrobial activity spectrum. The invention also discloses a preparation method of the antibacterialdrug. The method comprises the step of introducing the tetrazole ring to obtain 2-(2,4-difluorophenyl)-1-(1H-1,2,4-triazol-1-yl)-3-(1H-1,2,3,4-tetrazol-1-yl)-2-propanol on the basis of retaining moststructures with drug effects on fluconazole.

Continuous Flow Synthesis of Terminal Epoxides from Ketones Using in Situ Generated Bromomethyl Lithium

A scalable procedure for the direct preparation of epoxides from ketones has been developed. The method is based on the carefully controlled generation of (bromomethyl)lithium (LiCH2Br) from inexpensive CH2Br2 and MeLi in a continuous flow reactor. The reaction has shown excellent selectivity for a variety of substrates, including α-chloroketones, which typically fail under classic Corey-Chaykovsky conditions. This advantage has been used to develop a novel route toward the drug fluconazole.

A new exploration towards aminothiazolquinolone oximes as potentially multi-targeting antibacterial agents: Design, synthesis and evaluation acting on microbes, DNA, HSA and topoisomerase IV

This work did a new exploration towards aminothiazolquinolone oximes as potentially multi-targeting antimicrobial agents. A class of novel hybrids of quinolone, aminothiazole, piperazine and oxime fragments were designed for the first time, conveniently synthesized as well as characterized by 1H NMR, 13C NMR and HRMS spectra. Biological activity showed that some of the synthesized compounds exhibited good antimicrobial activities in comparison with the reference drugs. Especially, O-methyl oxime derivative 10b displayed excellent inhibitory efficacy against MRSA and S. aureus 25923 with MIC values of 0.009 and 0.017 mM, respectively. Further studies indicated that the highly active compound 10b showed low toxicity toward BEAS-2B and A549 cell lines and no obvious propensity to trigger the development of bacterial resistance. Quantum chemical studies have also been conducted and rationally explained the structural features essential for activity. The preliminarily mechanism exploration revealed that compound 10b could not only exert efficient membrane permeability by interfering with the integrity of cells, bind with topoisomerase IV–DNA complex through hydrogen bonds and π-π stacking, but also form a steady biosupramolecular complex by intercalating into DNA to exert the efficient antibacterial activity. The supramolecular interaction between compound 10b and human serum albumin (HSA) was a static quenching, and the binding process was spontaneous, where hydrogen bonds and van der Waals force played vital roles in the supramolecular transportation of the active compound 10b by HSA.

METALLOENZYME INHIBITOR COMPOUNDS

Provided are compounds having HDAC6 modulating activity, and methods of treating diseases, disorders or symptoms thereof mediated by HDAC6.

Novel carbazole-triazole conjugates as DNA-targeting membrane active potentiators against clinical isolated fungi

A series of carbazole-triazole conjugates were designed, synthesized and characterized by IR, NMR, and HRMS spectra. Biological assay showed that most of the synthesized compounds exhibited moderate and even strong antifungal activities, especially 3,6-dibromocarbazolyl triazole 5d displayed excellent inhibitory efficacy against most of the tested fungal strains (MIC = 2–32 μg/mL) and effectively fungicidal ability towards C. albicans, C. tropicals and C. parapsilosis ATCC 22019 (MFC = 4–8 μg/mL). Its combination use with fluconazole could enhance the antifungal efficacy, and compound 5d also did not obviously trigger the development of resistance in C. albicans even after 10 passages. Preliminary mechanism study revealed that the active molecule 5d could depolarize fungal membrane potential and intercalate into DNA to possibly block DNA replication, thus possibly exhibiting its powerful antifungal abilities. Conjugate 5d could interact with HSA, which was constructive for the further design, modification and screening of drug molecules. Docking investigation demonstrated a non-covalent binding of 5d with CYP51 through hydrogen bond and hydrophobicity. These results strongly suggested that compound 5d could act as a potential template for the development of promising antifungal drugs.

Mild Homologation of Esters through Continuous Flow Chloroacetate Claisen Reactions

The selective chloromethylenation of functionalized esters using chloroacetic acid (CA) and LiHMDS (HMDS=hexamethyldisilazide) in a continuous-flow setup is reported. This Claisen homologation is for the first time extended to bis-chloromethylenation using dichloroacetic acid (DCA), thus giving access to under-explored α,α′-bis-chloroketones. The use of flow conditions enables efficient generation and reaction of the unstable chloroacetate dianion intermediates, leading to unprecedented mild and scalable reaction conditions at an economical reagent stoichiometry (?10 °C, 1 min, 1.0–2.4 equiv dianion). The clean reaction profiles allow subsequent use of the unpurified crude products, which is demonstrated in the synthesis of various heterocycles of broad interest. Furthermore, we report a novel, catalyst-free substitution of the obtained monochloro ketone products with (hetero)aryl zinc enolates to give valuable 1,4-diketones.

Iridium-Catalyzed Asymmetric Hydrogenation of Halogenated Ketones for the Efficient Construction of Chiral Halohydrins

Iridium-catalyzed asymmetric hydrogenation of prochiral halogenated ketones was successfully developed to prepare various chiral halohydrins with high reactivities and excellent enantioselectivities under basic reaction condition (up to >99% conversion, 99% yield, >99% ee). Moreover, gram-scale experiment was performed well in the presence of just 0.005 mol% (S/C=20 000) Ir/f-amphox catalyst with 99% yield and >99% ee. (Figure presented.).