299933-96-3

Basic information

• Product Name: 5-{[(2,4-dichlorophenyl)methyl]sulfanyl}-1,3,4-thiadiazol-2-amine
• Synonyms: 5-{[(2,4-dichlorophenyl)methyl]sulfanyl}-1,3,4-thiadiazol-2-amine
• CAS NO: 299933-96-3
• Molecular Formula: C9H7Cl2N3S2
• Molecular Weight: 292.21
• Mol File: 299933-96-3.mol

Chemical Properties

• Appearance: /
• CAS DataBase Reference: 5-{[(2,4-dichlorophenyl)methyl]sulfanyl}-1,3,4-thiadiazol-2-amine(CAS DataBase Reference)
• NIST Chemistry Reference: 5-{[(2,4-dichlorophenyl)methyl]sulfanyl}-1,3,4-thiadiazol-2-amine(299933-96-3)
• EPA Substance Registry System: 5-{[(2,4-dichlorophenyl)methyl]sulfanyl}-1,3,4-thiadiazol-2-amine(299933-96-3)

Safety Data

• Hazardous Substances Data: 299933-96-3(Hazardous Substances Data)

Upstream product

• 2349-67-9 2-Amino-5-mercapto-1,3,4-thiadiazole 
• 20443-99-6 2,4-dichlorobenzyl bromide 
• 94-99-5 2,4-Dichlorobenzyl chloride 

Relevant articles and documents

Synthesis and biological assessment of ciprofloxacin-derived 1,3,4-thiadiazoles as anticancer agents

The quinolone-3-carboxylic acid scaffold is essential structure for antibacterial activity of fluoroquinolones such as ciprofloxacin. Modification of 3-carboxylic functionality in this structure can be used for switching its activity from antibacterial to anticancer. Accordingly, a series of C-3 modified ciprofloxacin derivatives containing N-(5-(benzylthio)-1,3,4-thiadiazol-2-yl)-carboxamide moiety was synthesized as novel anticancer agents. Most of compounds showed significant activity against MCF-7, A549 and SKOV-3 cancer cells in the MTT assay. In particular, compounds 13a-e and 13g were found to be as potent as standard drug doxorubicin against MCF-7 cell line (IC50s = 3.26–3.90 μM). Furthermore, the 4-fluorobenzyl derivatives 13h and 14b with IC50 values of 3.58 and 2.79 μM exhibited the highest activity against SKOV-3 and A549 cells, being as potent as doxorubicin. Two promising compounds 13e and 13g were further tested for their apoptosis inducing activity and cell cycle arrest. Both compounds could significantly induce apoptosis in MCF-7 cells, while compound 13e was more potent apoptosis inducer resulting in an 18-fold increase in the proportion of apoptotic cells at the IC50 concentration in MCF-7 cells. The cell cycle analysis revealed that compounds 13e and 13g could increase cell portions in the sub-G1 phase, inducing oligonucleosomal DNA fragmentation and apoptosis confirmed by comet assay.

Synthesis and radioligand-binding assay of 2,5-disubstituted thiadiazoles and evaluation of their anticonvulsant activities

In this study, a number of 2,5-disubstituted 1,3,4-thiadiazoles were synthesized using an appropriate synthetic route, and their anticonvulsant activity was determined by the maximal electroshock seizure (MES) test and their neurotoxicity was evaluated by the rotarod test. Additionally, their hypnotic activity was tested using the pentobarbital-induced sleep test. Compounds 7 (ED50 = 1.14 and 2.72 μmol/kg in the MES and sleep tests, respectively) and 11 (ED50 = 0.65 and 2.70 μmol/kg in the MES and sleep tests, respectively) were the most potent ones in the sleep test and anticonvulsant test, showing a comparable activity with diazepam as the reference drug. The results of in vivo studies, especially the antagonistic effects of flumazenil, and also the radioligand-binding assay confirmed the involvement of benzodiazepine (BZD) receptors in the anticonvulsant and hypnotic activity of compounds 7 and 11. Finally, the docking study of compound 11 in the BZD-binding site of the GABAA (gamma-aminobutyric acid) receptor confirmed the possible binding of the compound to the BZD receptors. We concluded that the novel 1,3,4-thiadiazole derivatives with appropriate substitution at positions 2 and 5 of the heterocyclic ring had a good affinity to BZD receptors and showed significant efficacy in the pharmacological tests.

Design, synthesis, and biological evaluation of 1-(5-(benzylthio)-1,3,4-thiadiazol-2-yl)-3-phenylurea derivatives as anticancer agents

A novel series of 1-(5-(benzylthio)-1,3,4-thiadiazol-2-yl)-3-phenylurea derivatives (5a–l) were designed and synthesized as sorafenib analogs. The in vitro cytotoxicity effects of synthesized compounds were evaluated against four different human cancer cells including MCF-7, HepG2, A549, and HeLa cell lines. The biological results showed that most of the compounds significantly prevented the proliferation of tested cancer cells. In particular, 2-F, 4-Cl, and 2,6-diF substituted derivatives (5d, 5g, and 5k) showed promising activities, especially against Hela cancer cells (IC50 = 0.37, 0.73 and 0.95 μM, respectively) which were significantly more potent than sorafenib as the reference drug (IC50 = 7.91 μM). Flow cytometry analysis revealed that the prototype compounds (5d, 5g, and 5k) significantly induced apoptotic cell death in HeLa cancer cells and blocked the cell cycle at the sub-G1 phase. Moreover, in silico docking study confirmed the binding of the prototype compound to the active site of VEGFR-2.

Ultrasound-assisted improved synthesis of 5-(benzylthio)-1,3,4-thiadiazol-2-amine derivatives: an experimental and computational study

The main objects of this study are: (1) to propose alternative efficient methods for the synthesis of 5-amino-1,3,4-thiadiazole-2-thiol and 5-(benzylthio)-1,3,4-thiadiazol-2-amine derivatives, (2) to investigate the reactions and the chemical species which take place in the investigated reactions computationally via density functional theory (DFT) calculations, (3) to make a comparison between experimental and computationally obtained data, and (4) to make a comparison between the computational methods to find out the best computational technique to simulate the investigated molecules and reactions. The study consists of two parts. In the first part, synthesis of 5-amino-1,3,4-thiadiazole-2-thiol and 5-(benzylthio)-1,3,4-thiadiazol-2-amine derivatives have been carried out. For both syntheses, it has been proposed that the reactions can be carried out effectively with the use of ultrasound. To the best of our knowledge, this is the first use of ultrasound for both reactions. The results showed that ultrasound can increase the efficiency of the investigated reactions and can be a good alternative to conventional methods. In the second part of the study, some DFT calculations have been performed on the chemical species which take place in the investigated reactions. In computational studies, seven different basis sets have been used. In this second part, comparisons have been made (1) between experimental and computationally obtained data, and (2) between the computational techniques to reveal the best method for the investigated molecules.

Design, synthesis and anti-bacterial evaluation of novel 1,3,4-thiadiazole derivatives bearing a semicarbazone moiety

Novel 1,3,4-thiadiazole derivatives bearing a semicarbazone moiety were prepared and evaluated for their anti-bacterial activities against Xanthomonas oryzae pv. oryzae (Xoo) and Xanthomonas axonopodis pv. citri (Xac) by performing a turbidimetre test. The products were structurally characterised by IR, 1H NMR, 13C NMR, 19F NMR and HRMS. Anti-bacterial testing showed that most of the evaluated compounds (6a-6s) exhibited excellent activity (≥74.19%) against Xoo at a concentration of 200?μg/mL, with 50% effective concentration (EC50) values ranging from 12.21 to 67.20?μg/mL, which were superior to the commercial antibacterial agent bismerthiazol (92.23?μg/mL). Among them, compound 2-((2-chloro-1H-indol-3-yl)methylene)-N-(5-((2-chlorobenzyl)thio)-1,3,4-thiadiazol-2-yl)hydrazine-1-carboxamide (6b) demonstrated good inhibitory activity against Xac (89.46% at 200?μg/mL) and Xoo (EC50 = 18.28?μg/mL); compound 2-((2-chloro-1H-indol-3-yl)methylene)-N-(5-((4-methoxybenzyl)thio)-1,3,4-thiadiazol-2-yl)hydrazine-1-carboxamide (6g) displayed excellent activity against Xoo with EC50 value of 12.21?μg/mL.

Design, synthesis, and biological activity of novel myricetin derivatives containing amide, thioether, and 1,3,4-thiadiazole moieties

A series of myricetin derivatives containing amide, thioether, and 1,3,4-thiadiazole moieties were designed and synthesized, and their antiviral and antibacterial activities were assessed. The bioassays showed that all the title compounds exhibited potent in vitro antibacterial activities against Xanthomonas citri (Xac), Ralstonia solanacearum (Rs), and Xanthomonas oryzae pv. Oryzae (Xoo). In particular, the compounds 5a, 5f, 5g, 5h, 5i, and 5l, with EC50 values of 11.5–27.3 μg/mL, showed potent antibacterial activity against Xac that was better than the commercial bactericides Bismerthiazol (34.7 μg/mL) and Thiodiazole copper (41.1% μg/mL). Moreover, the in vivo antiviral activities against tobacco mosaic virus (TMV) of the target compounds were also tested. Among these compounds, the curative, protection, and inactivation activities of 5g were 49.9, 52.9, and 73.3%, respectively, which were better than that of the commercial antiviral Ribavirin (40.6, 51.1, and 71.1%, respectively). This study demonstrates that myricetin derivatives bearing amide, thioether, and 1,3,4-thiadiazole moieties can serve as potential alternative templates for the development of novel, highly efficient inhibitors against plant pathogenic bacteria and viruses.

Containing substituted 1, 3, 4-thiadiazole sulfide pyrazole amide and pyrazole imine derivatives and preparation method and application

The invention discloses pyrazole amide and pyrazole imine derivatives containing substituted 1, 3, 4-thiadiazole thioether as well as a preparation method and an application of the derivatives. The compounds have the structures as shown in formulae (I) and (II). The preparation method comprises the following steps: by taking substituted hydrazine as an initial raw material, carrying out closed loop, chlorine formylation, oxidation and chloro reaction to obtain pyrazole acyl chloride; carrying out a reaction on 2-amino-5-mercapto-1, 3, 4-thiadiazole and substituted benzyl chloride to obtain 2-amino-5-substituted 1, 3, 4-thiadiazole thioether; and then, carrying out a substitution reaction on 2-amino-5-substituted 1, 3, 4-thiadiazole thioether and substituted pyrazole acyl chloride to obtain the pyrazole amide compound (I) containing substituted 1, 3, 4-thiadiazole thioether; by taking substituted hydrazine as an initial raw material, carrying out closed loop and chlorine formylation to obtain pyrazole aldehyde; carrying out an additive elimination reaction on pyrazole aldehyde and 2-amino-5-mercapto-1, 3, 4-thiadiazole under a backflow condition of anhydrous ethanol to obtain 2-substituted pyrazole imidogen-5-mercapto-1, 3, 4-thiadiazole; and then carrying out a reaction on 2-substituted pyrazole imidogen-5-mercapto-1, 3, 4-thiadiazole and substituted benzyl chloride to generate the pyrazole imine compound (II) containing substituted 1, 3, 4-thiadiazole thioether. The compounds disclosed by the invention have a good inhibiting effect on tobacco mosaic virus and can be used for preparing anti-plant virus drugs.

Nitrogen-containing heterocyclic 1, 3, 4-thiadiazole amide derivatives, and their preparation and use

The invention discloses xanthomonas oryzae or ralstonia solanacearum resistant compounds, namely 1, 3, 4-thiadiazole amide derivatives containing the nitrogen heterocyclic rings as well as a preparation method and biological activities of the 1, 3, 4-thiadiazole amide derivatives containing the nitrogen heterocyclic rings, wherein the compounds are shown in the following general formula (I) and (II). The preparation method comprises the following steps of with thiosemicarbazide, carbon disulfide, substituted chlorobenzyl (bromobenzyl), chloroacetyl chloride, piperazine anhydrous, N-methyl piperazine and morpholine as raw materials, closing loops, substituting and carrying out other reactions to synthesize a series of 1, 3, 4-thiadiazole amide compounds containing the nitrogen heterocyclic rings. The compounds synthesized by the invention have favorable activities on xanthomonas oryzae.