3268-74-4

Usage

Uses

Used in Pharmaceutical Industry:
2-CHLORO-N-(6-ETHOXY-BENZOTHIAZOL-2-YL)-ACETAMIDE is used as a pharmaceutical intermediate for the synthesis of various drugs and bioactive compounds. Its structural properties make it a valuable component in the development of new pharmaceuticals, potentially leading to innovative treatments and therapies.
Used in Agrochemical Development:
In the agrochemical industry, 2-CHLORO-N-(6-ETHOXY-BENZOTHIAZOL-2-YL)-ACETAMIDE may be utilized as a precursor in the creation of new agrochemicals. Its potential applications in this field could contribute to the development of more effective and targeted pest control solutions, enhancing agricultural productivity and sustainability.
Used in Organic Synthesis:
2-CHLORO-N-(6-ETHOXY-BENZOTHIAZOL-2-YL)-ACETAMIDE serves as a building block in organic synthesis, allowing chemists to construct complex molecules with specific properties and functions. Its unique structure and reactivity make it a useful component in the synthesis of a wide range of organic compounds for various applications, including materials science, pharmaceuticals, and agrochemicals.

InChI:InChI=1/C11H11ClN2O2S/c1-2-16-7-3-4-8-9(5-7)17-11(13-8)14-10(15)6-12/h3-5H,2,6H2,1H3,(H,13,14,15)

Upstream product

• 94-45-1 2-Amino-6-ethoxybenzothiazole 
• 79-04-9 chloroacetyl chloride 
• 90180-69-1 C₉H₁₀N₂OS*BrH 
• 156-43-4 4-Ethoxyaniline 
• 880-29-5 1-(4-ethoxyphenyl)thiourea 
• 541-88-8 Chloroacetic anhydride 

Downstream Products

• 1355611-88-9 N-(6-ethoxybenzothiazol-2-yl)-2-[[5-(2-cyclohexylethyl)-1,3,4-oxadiazol-2-yl]sulfanyl]acetamide 
• 1373946-43-0 2-((4-(4,6-bis(3,5-dimethylpiperidin-1-yl)-1,3,5-triazin-2-yl)phenyl)amino)-N-(6-ethoxybenzo[d]thiazol-2-yl)acetamide 
• 540513-50-6 C₁₈H₁₆N₆O₂S₂ 
• 665024-59-9 2-(5-amino-1,3,4-thiadiazol-2-yl)thio-N-(6-ethoxybenzothiazol-2-yl)acetamide 
• 1355611-83-4 N-(6-ethoxybenzothiazol-2-yl)-2-[[5-(4-methoxyphenoxymethyl)-1,3,4-oxadiazol-2-yl]sulfanyl]acetamide 
• 1276539-06-0 4-(6-ethoxy-1,3-benzothiazol-2-yl)amino-2-(4-chlorophenyl)amino-1,3-thiazole 
• 1276539-05-9 4-(6-ethoxy-1,3-benzothiazol-2-yl)amino-2-phenylamino-1,3-thiazole 
• 1276539-08-2 4-(6-ethoxy-1,3-benzothiazol-2-yl)amino-2-(4-methoxyphenyl)amino-1,3-thiazole 
• 1276539-07-1 4-(6-ethoxy-1,3-benzothiazol-2-yl)amino-2-(4-hydroxyphenyl)amino-1,3-thiazole 
• 872057-69-7 C₂₁H₂₄N₄O₂S 
• 3320-61-4 6-Ethoxy-2--benzothiazole 
• 3320-78-3 6-Ethoxy-2-(N-benzimidazolyl-acetylamino)-benzothiazole 

Relevant academic research and scientific papers

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.

Mechanistic insights into binding of ligands with thiazolidinedione warhead to human histone deacetylase 4

Recently, we have reported that non-hydroxamate thiazolidinedione (TZD) analogs are capable of inhibiting human deacetylase 4 (HDAC4). This study aims at the dissection of the molecular determinants and kinetics of the molecular recognition of TZD ligands by HDAC4. For this purpose, a structure activity relationship analysis of 225 analogs was combined with a comprehensive study of the enzyme and binding kinetics of a variety of HDAC4 mutant variants. The experimental data were rationalized by docking to the two major conformations of HDAC4. TZD ligands are competitive inhibitors and bind via a two-step mechanism involving principal molecular recognition and induced fit. The residence time of 24 g is (34 ± 3) min and thus much larger than that of the canonical pan-HDAC inhibitor SAHA ((5 ± 2) min). Importantly, the binding kinetics can be tuned by varying the structure of the CAP group.

Biological evaluation of a series of benzothiazole derivatives as mosquitocidal agents

Aedes aegypti is associated with the transmission of numerous human and animal diseases, such as yellow fever, dengue fever, chikungunya, and more recently Zika virus. Emerging insecticide resistance has created a need to develop new mosquitocidal agents for effective control operations. A series of benzothiazole-piperidine derivatives (1-24) were investigated for their larvicidal and adulticidal effects on Ae. aegypti It was observed that compounds 2, 4, 6, 7, 8, 11 and 13 showed notable larvicidal activity. Furthermore, compounds 6 and 10 showed promising adulticidal activity. Based on the mosquitocidal properties of these compounds, docking studies were also carried out in the active site of the AeSCP2 enzyme to explore any insights into further in vitro enzyme studies. Docking results indicated that all these active compounds showed reasonable interactions with critical residues in the active site of this enzyme. This outcome suggested that these compounds might show their larvicidal and adulticidal effects via the inhibition of AeSCP2. According to in vitro and in silico studies, compounds 2, 4, 6, 7, 8, 10, 11 and 13 stand out as candidates for further studies.

Design, synthesis, and biological evaluation of novel 1,3,4-thiadiazole derivatives as potential antitumor agents against chronic myelogenous leukemia: Striking effect of nitrothiazole moiety

In an attempt to develop potent antitumor agents, new 1,3,4-thiadiazole derivatives were synthesized and evaluated for their cytotoxic effects on multiple human cancer cell lines, including the K562 chronic myelogenous leukemia cell line that expresses the Bcr-Abl tyrosine kinase. N-(5-Nitrothiazol-2-yl)-2-((5-((4-(trifluoromethyl)phenyl)amino)-1,3,4-thiadiazol-2-yl)thio)acetamide (2) inhibited the Abl protein kinase with an IC50 value of 7.4 μM and showed selective activity against the Bcr-Abl positive K562 cell line. Furthermore, a Bcr-Abl-compound 2 molecular modelling simulation highlighted the anchoring role of the nitrothiazole moiety in bonding and hydrophobic interaction with the key amino acid residues. These results provide promising starting points for further development of novel kinase inhibitors.

Fighting against alzheimer’s disease: Synthesis of new pyrazoline and benzothiazole derivatives as new acetylcholinesterase and MAO inhibitors

Background: Alzheimer’s Disease (AD) is a complicated neurodegenerative disorder with a multifaceted pathogenesis.AD, characterized by gradual memory loss, falling in language ability and other cognitive deterioration, and has been a prominent risk to ageing population. This means that there is an urgent need to find new lead compounds for controlling and fighting against (AD). In this way, a new thiophene-2-pyrazoline derivatives (A1-A5) and benzothiazole derivatives (A6-A13) have been synthesized to give beneficial compounds to controlling and battling against (AD). Results: Compounds A5 and A13 showed the most remarkable activity with an 18.53 μM and 15.26 μM IC50 values against AChE enzyme. In like manner, compound A4 was active with a 20.34 μM IC50 value against MAO-A. These active compounds are in fact non-toxic making them very attractive for additional future studies. Enzyme kinetic was analyzed and the Lineweaver-Burk plot reveals that compound A13 was typically mixed AChE inhibitors, which showed significant similarity to donepezil. In addition, the best docking pose was done by analyzing the docking pattern of the most active compound A13 which was very compatible with the gorge and in interaction with both CAS and PAS. Conclusion: The synthesis of new thiophene-2-pyrazoline and benzothiazole derivatives targeting AChE/(MAO-A)/(MAO-B) enzymes was described. The selection of enzyme-kinetic analysis, molecular docking and toxicity test was led to good understanding to the therapeutic potential for the active derivatives. Therefore, these compounds may be accepted as promising leads for future research efforts in fighting against AD.

Design, synthesis, in vitro and in silico evaluation of a new series of oxadiazole-based anticancer agents as potential Akt and FAK inhibitors

In the current work, new 1,3,4-oxadiazole derivatives were synthesized and investigated for their cytotoxic effects on A549 human lung adenocarcinoma, C6 rat glioma and NIH/3T3 mouse embryonic fibroblast cell lines. Compounds 2, 6 and 9 were found to be the most potent anticancer agents against A549 and C6 cell lines and therefore their effects on apoptosis, caspase-3 activation, Akt, FAK, mitochondrial membrane potential and ultrastructural morphological changes were evaluated. N-(5-Nitrothiazol-2-yl)-2-[[5-[((5,6,7,8-tetrahydronaphthalen-2-yl)oxy)methyl]-1,3,4-oxadiazol-2-yl]thio]acetamide (9) increased early and late apoptotic cell population in A549 and C6 cells more than cisplatin and caused more mitochondrial membrane depolarization in both cell lines than cisplatin. On the other hand, N-(6-methoxybenzothiazol-2-yl)-2-[[5-[((5,6,7,8-tetrahydronaphthalen-2-yl)oxy)methyl]-1,3,4-oxadiazol-2-yl]thio]acetamide (6) caused higher caspase-3 activation than cisplatin in both cell lines. Compound 6 showed significant Akt inhibitory activity in both cell lines. Moreover, compound 6 significantly inhibited FAK (Phospho-Tyr397) activity in C6 cell line. Molecular docking simulations demonstrated that compound 6 fitted into the active sites of Akt and FAK with high affinity and substrate-specific interactions. Furthermore, compounds 2, 6 and 9 caused apoptotic morphological changes in both cell lines obtained from micrographs by transmission electron microscopy. A computational study for the prediction of ADME properties of all compounds was also performed. These compounds did not violate Lipinski's rule, making them potential orally bioavailable anticancer agents.

Aminothiazoles as Potent and Selective Sirt2 Inhibitors: A Structure-Activity Relationship Study

Sirtuins are NAD+-dependent protein deacylases that cleave off acetyl but also other acyl groups from the ε-amino group of lysines in histones and other substrate proteins. Dysregulation of human Sirt2 (hSirt2) activity has been associated with the pathogenesis of cancer, inflammation, and neurodegeneration, which makes the modulation of hSirt2 activity a promising strategy for pharmaceutical intervention. The sirtuin rearranging ligands (SirReals) have recently been discovered by us as highly potent and isotype-selective hSirt2 inhibitors. Here, we present a well-defined structure-activity relationship study, which rationalizes the unique features of the SirReals and probes the limits of modifications on this scaffold regarding inhibitor potency. Moreover, we present a crystal structure of hSirt2 in complex with an optimized SirReal derivative that exhibits an improved in vitro activity. Lastly, we show cellular hyperacetylation of the hSirt2 targeted tubulin caused by our improved lead structure.

Synthesis and antimicrobial activity evaluation of new dithiocarbamate derivatives bearing thiazole/benzothiazole rings

The synthesis of 2-(substituted phenyl)-2-oxoethyl 4-(pyrimidin-2-yl)piperazin-1-carbodithiodate (A1-A24) derivatives and 2-(4-substituted thiazol-2-ylamino)-2-oxoethyl 4-(pyrimidin-2-yl)piperazin-1-carbodithiodate (B1-B14) derivatives was undertaken starting from the potassium salt of 4-(2-pyrimidinyl)piperazine dithiocarbamate. The structures of the obtained compounds were elucidated by1H NMR,13C NMR, MS spectral data, and elemental analysis. The antimicrobial activity of the thirty eight newly synthesized compounds were tested against 12 microorganism strains using the microdilution technique. Compounds 2-(4-ethoxycarbonylthiazol-2-ylamino)-2-oxoethyl 4-(pyrimidin-2-yl)piperazin-1-carbodithiodate (B12), 2-(3-fluorophenyl)-2-oxoethyl 4-(pyrimidin-2-yl)piperazin-1-carbodithiodate (A18) and 2-(3,4-difluorophenyl)-2-oxoethyl 4-(pyrimidin-2-yl)piperazin-1-carbodithiodate (A21) were determined to possess high antimicrobial activity.

Catalytic N-formylation for synthesis of 6-substituted-2-benzothiazolylimino-5-piperazinyl-4-thiazolidinone antimicrobial agents

A new class of piperazine-based 2-benzothiazolylimino-4-thiazolidinones has been efficiently prepared via highly accelerated N-formylation of N-isopropylpiperazine by the use of a mild heterogeneous catalyst, sulfated tungstate. Heterocyclization of N-(benzo[d]thiazol-2-yl)-2-chloroacetamides (3a-j) by use of NH4SCN in ethanol under reflux efficiently furnished the intermediates 2-benzothiazolyliminothiazolidin-4-ones (4a-j). These were treated with 4-isopropylpiperazine-1-carbaldehyde (2) to prepare the final products 5a-j. The structures of the new derivatives were confirmed by elemental analysis and use of spectroscopic data (FTIR and 1H NMR). Their pharmacological potential as promising antimicrobial agents was determined in vitro against bacteria and a fungus; the lowest minimum inhibitory concentrations (MIC) observed were in the range 4-8 μg/mL.

Cytotoxic activities of some benzothiazole-piperazine derivatives

Synthesis, characterization and cytotoxic activities of ten benzothiazole-piperazine derivatives were reported. In vitro cytotoxic activities of compounds were screened against hepatocellular (HUH-7), breast (MCF-7) and colorectal (HCT-116) cancer cell li