7420-37-3

Upstream product

• 79-19-6 thiosemicarbazide 
• 100-83-4 meta-hydroxybenzaldehyde 

Downstream Products

• 128192-80-3 Cu⁽¹⁺⁾*C₈H₈N₃OS^(1-)={Cu(C₆H₄(OH)CHNNCSNH₂)} 
• 333776-51-5 2-(2-(3-hydroxybenzylidene)hydrazinyl)thiazol-4(5H)-one 

Relevant academic research and scientific papers

Synthesis, antimicrobial and antioxidant evaluation with in silico studies of new thiazole Schiff base derivatives

A series of nineteen thiazole Schiff base derivatives 2a-2s were synthesized (Scheme 1) and elucidated by spectral analyses (IR, 1H NMR and HRMS). The evaluation of their antimicrobial activities against two gram-positive, two gram-negative, an

Thiazole derivatives and preparation method and application thereof

The invention discloses thiazole derivatives and a preparation method and application thereof. The structural formula of the thiazole derivatives is shown as a formula (IV). A series of thiazole derivatives with brand-new structures are designed and synthesized by introducing a lipophilic side chain to the C2 position of a thiazole ring and introducing a hydrophilic guanidyl to the C5 position of the thiazole ring. The preparation method comprises the following steps: by taking an aldehyde compound (I) and thiosemicarbazide as raw materials, carrying out condensation reaction to obtain a first-step product (II), and reacting the first-step product (II) with 3-chloroacetylacetone to obtain a second-step product (III); and reacting the second-step product (III) with aminoguanidine hydrochloride to prepare a final product (IV). The heterozygote shows antibacterial activity, particularly has good antibacterial activity on staphylococcus aureus, escherichia coli and pseudomonas aeruginosa, and can be used as an antibacterial candidate compound.

Synthesis, characterization, alkaline phosphatase inhibition assay and molecular modeling studies of 1-benzylidene-2-(4-tert- butylthiazol-2-yl) hydrazines

Alkaline phosphatases are homodimeric protein enzymes which removes phosphates from several types of molecules. These catalyze the hydrolysis of monoesters in phosphoric acid which in turn catalyze a transphosphorylation reaction. Thiazoles are a privileged class of heterocyclic compounds which may potentially serve as effective phosphatase inhibitors. In this regard, the present research paper reports the facile synthesis and characterization of substituted 1-benzylidene-2-(4-tert-butylthiazol-2-yl) hydrazines with excellent yields. The synthesized compounds were tested for inhibitory potential against alkaline phosphatases. The compound 1-(4-Hydroxy, 3-methoxybenzylidene)-2-(4-tert-butylthiazol-2-yl) hydrazine (5e) was found to be the most potent inhibitor of human tissue non-alkaline phosphatase in this group of molecules with an IC50 value of 1.09 ± 0.18 μM. The compound 1-(3,4-dimethoxybenzylidene)-2-(4-tert-butylthiazol-2-yl) hydrazine (5d) exhibited selectivity and potency for human intestinal alkaline phosphatase with an IC50 value of 0.71 ± 0.02 μM. In addition, structure activity relationship and molecular docking studies were performed to evaluate their binding modes with the target site of alkaline phosphatase. The docking analysis revealed that the most active inhibitors showed the important interactions within the binding pockets of human intestinal alkaline phosphatase and human tissue non-alkaline phosphatase and may be responsible for the inhibitory activity of the compound towards the enzymes. Therefore, the screened thiazole derivatives provided an outstanding platform for further development of alkaline phosphatase inhibitors.

Design, synthesis and biological assessment of new selective COX-2 inhibitors including methyl sulfonyl moiety

Nonsteroidal anti-inflammatory drugs (NSAIDs) cause peptic lesions in the gastrointestinal mucosa by inhibiting the cyclooxygenase-1 (COX-1) enzyme. Selective COX-2 inhibition causes decreased side effects over current NSAIDs. Therefore, the studies about selective inhibition of COX-2 enzyme are very important for new drug development. The design, synthesis and biological activity evaluation of novel derivatives bearing thiazolylhydrazine-methyl sulfonyl moiety as selective COX-2 inhibitors were aimed in this paper. The structures of synthesized compounds were assigned using different spectroscopic techniques such as 1H NMR, 13C NMR and HRMS. In addition, the estimation of ADME parameters for all compounds was carried out using in silico process. The evaluation of in vitro COX-1/COX-2 enzyme inhibition was applied according to the fluorometric method. According to the enzyme inhibition results, synthesized compounds showed the selectivity against COX-2 enzyme inhibition as expected. Compounds 3a, 3e, 3f, 3g, 3i and 3j demonstrated significant COX-2 inhibition potencies. Among them, compound 3a was found to be the most effective derivative with an IC50 value of 0.140 ± 0.006 μM. Moreover, it was seen that compound 3a displayed a more potent inhibition profile at least 12-fold than nimesulide (IC50 = 1.684 ± 0.079 μM), while it showed inhibitory activity at a similar rate of celecoxib (IC50 = 0.132 ± 0.005 μM). Molecular modelling studies aided in the understanding of the interaction modes between this compound and COX-2 enzyme. It was found that compound 3a had a significant binding property. In addition, the selectivity of obtained derivatives on COX-2 enzyme could be explained and discussed by molecular docking studies.

Thiosemicarbazones exhibit inhibitory efficacy against New Delhi metallo-β-lactamase-1 (NDM-1)

The superbug infection caused by metallo-β-lactamases (MβLs) carrying drug-resistant bacteria, specifically, New Delhi metallo-β-lactamase (NDM-1) has become an emerging threat. In an effort to develop novel inhibitors of NDM-1, thirteen thiosemicarbazones (1a-1m) were synthesized and assayed. The obtained molecules specifically inhibited NDM-1, with an IC50 in the range of 0.88–20.2 μM, and 1a and 1f were found to be the potent inhibitors (IC50 = 1.79 and 0.88 μM) using cefazolin as substrate. ITC and kinetic assays indicated that 1a irreversibly and non-competitively inhibited NDM-1 in vitro. Importantly, MIC assays revealed that these molecules by themselves can sterilize NDM-producing clinical isolates EC01 and EC08, exhibited 78-312-fold stronger activities than the cefazolin. MIC assays suggest that 1a (16 μg ml?1) has synergistic antimicrobial effect with ampicillin, cefazolin and meropenem on E. coli producing NDM-1, resulting in MICs of 4-32-, 4-32-, and 4-8-fold decrease, respectively. These studies indicate that the thiosemicarbazide is a valuable scaffold for the development of inhibitors of NDM-1 and NDM-1 carrying drug-resistant bacteria.

Design, synthesis, and structure–Activity relationships of thiazole analogs as anticholinesterase agents for alzheimer’s disease

Dementia is a neurological condition commonly correlated with Alzheimer’s disease (AD), and it is seen with many other central nervous system (CNS) disorders. The restricted number of medications is not appropriate to offer enough relief to enhance the quality of life of patients suffering from this symptom; thus, all therapeutic choices should be carefully assessed. In this study, new thiazolylhydrazone derivatives (2a–2l) were designed and synthesized based on the cholinergic hypothesis. Their chemical structures were confirmed by 1H NMR, 13C NMR, and HRMS spectrometric techniques. The ADME (absorption, distribution, metabolism, elimination) parameters of the synthesized compounds were predicted by using QikProp 4.8 software. It was concluded that all compounds presented satisfactory drug-like characteristics. Furthermore, their inhibitory activities against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) in vitro were also tested by modified the Ellman spectrophotometric method. According to the results, all compounds showed a weak inhibitory effect on BChE. On the other hand, most of the compounds (2a, 2b, 2d, 2e, 2g, 2i, and 2j) had a certain AChE inhibitory activity, and the IC50 values of them were calculated as 0.063 ± 0.003, 0.056 ± 0.002, 0.147 ± 0.006, 0.040 ± 0.001, 0.031 ± 0.001, 0.028 ± 0.001, and 0.138 ± 0.005 μM, respectively. Among these derivatives, compound 2i was found to be the most active agent in the series with an IC50 value of 0.028 ± 0.001 μM, which indicated an inhibition profile at a similar rate as the reference drug, donepezil. The potential binding modes of compounds 2a, 2b, 2e, 2g, and 2i with AChE were investigated and compared with each other by the molecular docking studies. The results showed that these compounds were strongly bound up with the AChE enzyme active site with the optimal conformations.

Microwave Assisted Synthesis and Biological Activity of Novel Bis{2-[2-(substituted benzylidene)hydrazinyl]thiazole} Derivatives

Abstract—New 4,4'-(4,6-dimethoxy-1,3-phenylene)bis{2-[2-(substituted benzylidene)hydrazinyl]thiazole} derivatives (5a–5j) have been synthesized from the corresponding 1,1'-(4,6-dimethoxy-1,3-phenylene)bis(2,2- dibromoethanone) and substituted thiosemicarbazones by the conventional method and under microwave irradiation. Structures of the synthesized compounds were characterized by FT-IR, 1H, and 13C NMR and Mass spectra. The products were evaluated for their in vitro antibacterial activity against Gram-positive and Gramnegative stains. Some of the compounds 5b, 5f, 5h demonstrated high activity against B. subtilis (+ve), compound 5c exhibited high activity against E. coli (–ve) and P. aeruginosa (–ve) stains. Among the titled compounds also evaluated for their in vitro antimycobacterial activity, the product 5b demonstrated pronounced antimycobacterial activity against M. bovis stain.

2 - (2 - Animal pen asia jingjing base) -5 - acyl thiazole and its medical use (by machine translation)

The invention formula I shown by 2 - (2 - animal pen asia jingjing base) - 5 - acyl thiazole and its pharmaceutically acceptable salt, pharmaceutical composition and thereof in the preparation of influenza virus neuraminidase inhibitors in the application. Wherein R is selected from: methyl, ethyl, C3 - C4 Straight-chain or C3 - C4 Branched alkyl; R1 Is selected from: hydrogen, C1 - C2 Alkyl, C3 - C4 Straight-chain or C3 - C4 Branched alkyl, fluoromethyl, difluoromethyl, trifluoromethyl, bromomethyl, [...], three bromine methyl, chloromethyl, dichloro methyl or trichloromethyl; X1 , X5 Is selected from: hydrogen, deuterium, C1 - C2 Alkyl, hydroxy, methoxy, ethoxy, fluoro, chloro, bromo, iodo, nitro, amino, methylamino, dimethylamino, acetyl, carboxy, methoxycarbonyl or ethoxycarbonyl; X2 , X4 Is selected from: hydrogen, deuterium, C1 - C2 Alkyl, C3 - C4 Straight or branched chain alkyl, hydroxy, methoxy, ethoxy, fluoro, chloro, bromo, iodo, nitro, amino, methylamino, dimethylamino, acetyl, carboxy, methoxycarbonyl or ethoxycarbonyl; X3 Is selected from: hydrogen, deuterium, C1 - C2 Alkyl, hydroxy, methoxy, ethoxy, fluoro, chloro, bromo, iodo, nitro, amino, methylamino, dimethylamino, acetyl, carboxy, methoxycarbonyl or ethoxycarbonyl. (by machine translation)

One PotTwo Step Synthesis of 2-Arylidenehydrazinyl-4-arylthiazole

An efficient, simple one pot, two step procedure has been developed for the synthesis of 2-arylidenehydrazinyl-4-arylthiazole. The reaction of aromatic aldehyde, thiosemicarbazide and phenacyl bromide gave the desired products in good yield. The first reaction product thiosemicarbazone was obtained on reaction with aromatic aldehyde and thiosemicarbazide; without isolating this directly treated with phenacyl bromide in presence of acidic buffer at room temperature desired product was obtained with simple workup procedure.

In vitro and in silico antimalarial activity of 2-(2-hydrazinyl)thiazole derivatives

A series of 2-(2-hydrazinyl)thiazole derivatives with a wide range of substitutions at 2-, 4- and 5-positions were synthesized, characterized and evaluated their inhibitory potentials against plasmodium falciparum, NF54, by in vitro blood stage assay. The compounds, ethyl-4-methyl-2-[(E)-2-[1-(pyridin-2- yl)ethylidene]hydrazin-1-yl]-1,3-thiazole-5-carboxylate, 4d, and 1-{4-methyl-2-[(E)-2-[1-(pyridin-2-yl)ethylidene]hydrazin-1-yl]-1, 3-thiazol-5-yl}ethan-1-one, 5d showed significant antimalarial activity with IC50 values of 0.725 μM and 0.648 μM respectively. To understand the mechanism, the binding interactions between 2-(2-hydrazinyl) thiazole derivatives and trans-2-enoyl acyl carrier protein reductase of P. falciparum were studied through docking studies. The half maximal inhibitory concentration (IC50) through docking studies for the compounds, 4d and 5d were found to be 22.88 μM and 631.84 μM respectively.