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General Description

N-Chloroacetyl-2,4-difluoroaniline is a chemical compound with the molecular formula C8H6ClF2N. It is used as an intermediate in the synthesis of pharmaceuticals and agrochemicals. N-CHLOROACETYL-2,4-DIFLUOROANILINE is a chlorinated derivative of 2,4-difluoroaniline, making it useful in the production of various fluorinated organic compounds. It is important to handle this chemical with caution, as it is a potential irritant to the skin, eyes, and respiratory system. Additionally, it should be stored and used in a well-ventilated area with proper personal protective equipment to minimize exposure.

InChI:InChI=1/C8H6ClF2NO/c9-4-8(13)12-7-2-1-5(10)3-6(7)11/h1-3H,4H2,(H,12,13)

Upstream product

• 367-25-9 2,4-difluorophenylamine 
• 79-04-9 chloroacetyl chloride 
• 105-39-5 chloroacetic acid ethyl ester 

Downstream Products

• 183988-42-3 N-(2,4-Difluoro-phenyl)-2-(2-oxo-2-phenyl-ethylsulfanyl)-acetamide 
• 477320-15-3 N-(2,4-difluorophenyl)-2-[4-(2-pyridinyl)-1-piperazinyl]acetamide 
• 249933-10-6 N-(2,4-Difluorophenyl)-2-[5-methoxy-1-(toluene-4-sulphonyl)-1H-indazol-3-yloxy]acetamide 
• 454458-56-1 N-(2,4-difluorophenyl)-2-(5H-[1,2,4]triazino[5,6-b]indol-3-ylsulfanyl)acetamide 

Relevant academic research and scientific papers

Synthesis and Biological Evaluation of Dithiobisacetamides as Novel Urease Inhibitors

Thirty-eight disulfides containing N-arylacetamide were designed and synthesized in an effort to develop novel urease inhibitors. Biological evaluation revealed that some of the synthetic compounds exhibited strong inhibitory potency against both cell-free urease and urease in intact cell with low cytotoxicity to mammalian cells even at concentration up to 250 μM. Of note, 2,2′-dithiobis(N-(2-fluorophenyl)acetamide) (d7), 2,2′-dithiobis(N-(3,5-difluorophenyl)acetamide) (d24), and 2,2′-dithiobis(N-(3-fluorophenyl)acetamide) (d8) were here identified as the most active inhibitors with IC50 of 0.074, 0.44, and 0.81 μM, showing 32- to 355-fold higher potency than the positive control acetohydroxamic acid. These disulfides were confirmed to bind urease without covalent modification of the cysteine residue and to inhibit urease reversibly with a mixed inhibition mechanism. They also showed very good anti-Helicobacter pylori activities with d8 showing a comparable potency to the clinical used drug amoxicillin. The impressive in vitro biological profile indicated their immense potential as therapeutic agents to tackle H. pylori caused infections.

Synthesis, and in vitro biological evaluations of novel naphthoquinone conjugated to aryl triazole acetamide derivatives as potential anti-Alzheimer agents

Alzheimer's disease is a neurodegenerative disorder that deteriorates mental ability. Two main cholinesterases named, acetylcholinesterase and butyrylcholinesterase are potential targets against Alzheimer's disease. Cholinesterase inhibitors have benefici

Novel (thio)barbituric-phenoxy-N-phenylacetamide derivatives as potent urease inhibitors: synthesis, in vitro urease inhibition, and in silico evaluations

A novel series of (thio)barbituric-phenoxy-N-phenylacetamide derivatives 7a-l was synthesized and evaluated against Helicobacter pylori urease. The latter assay revealed that all the synthesized compounds 7a-l (IC50 = 0.69 ± 0.33–2.47 ± 0.23?μM

Thiazolidinedione "magic Bullets" Simultaneously Targeting PPARγand HDACs: Design, Synthesis, and Investigations of their in Vitro and in Vivo Antitumor Effects

Monotargeting anticancer agents suffer from resistance and target nonspecificity concerns, which can be tackled with a multitargeting approach. The combined treatment with HDAC inhibitors and PPARγagonists has displayed potential antitumor effects. Based on these observations, this work involves design and synthesis of molecules that can simultaneously target PPARγand HDAC. Several out of 25 compounds inhibited HDAC4, and six compounds acted as dual-targeting agents. Compound 7i was the most potent, with activity toward PPARγEC50 = 0.245 μM and HDAC4 IC50 = 1.1 μM. Additionally, compounds 7c and 7i were cytotoxic to CCRF-CEM cells (CC50 = 2.8 and 9.6 μM, respectively), induced apoptosis, and caused DNA fragmentation. Furthermore, compound 7c modulated the expression of c-Myc, cleaved caspase-3, and caused in vivo tumor regression in CCRF-CEM tumor xenografts. Thus, this study provides a basis for the rational design of dual/multitargeting agents that could be developed further as anticancer therapeutics.

Naproxen based 1,3,4-oxadiazole derivatives as EGFR inhibitors: Design, synthesis, anticancer, and computational studies

A library of novel naproxen based 1,3,4-oxadiazole derivatives (8–16 and 19–26) has been synthesized and screened for cytotoxicity as EGFR inhibitors. Among the synthesized hy-brids, compound2-(4-((5-((S)-1-(2-methoxynaphthalen-6-yl)ethyl)-1,3,4-oxadiazol-2-ylthio)methyl)-1H-1,2,3-triazol-1-yl)phenol(15) was the most potent compound against MCF-7 and HepG2cancer cells with IC50 of 2.13 and 1.63 μg/mL, respectively, and was equipotent to doxorubicin (IC50 1.62 μg/mL) towards HepG2. Furthermore, compound 15 inhibited EGFR kinase with IC50 0.41 μM compared to standard drug Erlotinib (IC50 0.30 μM). The active compound induces a high percentage of necrosis towards MCF-7, HePG2 and HCT 116 cells. The docking studies, DFT and MEP also supported the biological data. These results demonstrated that these synthesized naproxen hybrids have EGFR inhibition effects and can be used as leads for cancer therapy.

Discovery of 5-naphthylidene-2,4-thiazolidinedione derivatives as selective HDAC8 inhibitors and evaluation of their cytotoxic effects in leukemic cell lines

Histone deacetylases (HDACs) are being explored as a therapeutic target for interventions in different types of cancer. HDAC8 is a class I HDAC that is implicated as a therapeutic target in various indication areas, including different types of cancer and particularly childhood neuroblastoma. Most previously described HDAC8-selective inhibitors contain a hydroxamate function as zinc binding group (ZBG) to confer potency. However, hydroxamate class HDAC inhibitors have raised increasing concerns about their mutagenic character. Therefore, non-hydroxamate based inhibitors could prove to be safer than hydroxamates. In the present work, a series of novel 5-naphthylidene-2,4-thiazolidinedione was designed and evaluated as potential antiproliferative agents targeting selectively HDAC8 enzyme. Eleven novel derivatives were synthesized, purified and characterized by spectroscopic techniques. Compounds 3k and 3h was found to be most potent selective inhibitors of HDAC8 with IC50 values of 2.7 μM and 6.3 μM respectively. 3a to 3i was found to be most cytotoxic in leukemic cell lines. 3a and 3 h both were found to induce apoptosis and cause cell cycle arrest in G2/M phase.

Discovery of novel N-substituted thiazolidinediones (TZDs) as HDAC8 inhibitors: in-silico studies, synthesis, and biological evaluation

Epigenetics plays a fundamental role in cancer progression, and developing agents that regulate epigenetics is crucial for cancer management. Among Class I and Class II HDACs, HDAC8 is one of the essential epigenetic players in cancer progression. Therefore, we designed, synthesized, purified, and structurally characterized novel compounds containing N-substituted TZD (P1-P25). Cell viability assay of all compounds on leukemic cell lines (CEM, K562, and KCL22) showed the cytotoxic potential of P8, P9, P10, P12, P19, and P25. In-vitro screening of different HDACs isoforms revealed that P19 was the most potent and selective inhibitor for HDAC8 (IC50 – 9.3 μM). Thermal shift analysis (TSA) confirmed the binding of P19 to HDAC8. In-vitro screening of all compounds on the transport activity of GLUT1, GLUT4, and GLUT5 indicated that P19 inhibited GLUT1 (IC50 – 28.2 μM). P10 and P19 induced apoptotic cell death in CEM cells (55.19% and 60.97% respectively) and P19 was less cytotoxic on normal WBCs (CC50 – 104.2 μM) and human fibroblasts (HS27) (CC50 – 105.0 μM). Thus, among this novel series of TZD derivatives, compound P19 was most promising HDAC8 inhibitor and cytotoxic on leukemic cells. Thus, P19 could serve as a lead for further development of optimized molecules with enhanced selectivity and potency.

Synthesis, characterization, molecular docking, and biological activities of coumarin–1,2,3-triazole-acetamide hybrid derivatives

Coumarins and their derivatives are receiving increasing attention due to numerous biochemical and pharmacological applications. In this study, a series of novel coumarin–1,2,3-triazole-acetamide hybrids was tested against some metabolic enzymes including α-glycosidase (α-Gly), α-amylase (α-Amy), acetylcholinesterase (AChE), butyrylcholinesterase (BChE), human carbonic anhydrase I (hCA I), and hCA II. The new coumarin–1,2,3-triazole-acetamide hybrids showed Ki values in the range of 483.50–1,243.04 nM against hCA I, 508.55–1,284.36 nM against hCA II, 24.85–132.85 nM against AChE, 27.17–1,104.36 nM against BChE,?590.42–1,104.36 nM against α-Gly,?and 55.38–128.63 nM against α-Amy. The novel coumarin–1,2,3-triazole-acetamide hybrids had effective inhibition profiles against all tested metabolic enzymes. Also, due to the enzyme inhibitory effects of the new hybrids, they are potential drug candidates to treat diseases such as epilepsy, glaucoma, type-2 diabetes mellitus (T2DM), Alzheimer's disease (AD), and leukemia. Additionally, these inhibition effects were compared with standard enzyme inhibitors like acetazolamide (for hCA I and II), tacrine (for AChE and BChE), and acarbose (for α-Gly and α-Amy). Also, those coumarin–1,2,3-triazole-acetamide hybrids with the best inhibition score were docked into the active site of the indicated metabolic enzymes.

Structure guided design and synthesis of furyl thiazolidinedione derivatives as inhibitors of GLUT 1 and GLUT 4, and evaluation of their anti-leukemic potential

Cancer cells increase their glucose uptake and glycolytic activity to meet the high energy requirements of proliferation. Glucose transporters (GLUTs), which facilitate the transport of glucose and related hexoses across the cell membrane, play a vital ro

Permuted 2,4-thiazolidinedione (TZD) analogs as GLUT inhibitors and their in-vitro evaluation in leukemic cells

Cancer is a heterogeneous disease, and its treatment requires the identification of new ways to thwart tumor cells. Amongst such emerging targets are glucose transporters (GLUTs, SLC2 family), which are overexpressed by almost all types of cancer cells; t