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Usage

Uses

Used in Pharmaceutical Industry:
2-AMINO-5-(4-CHLOROBENZYLTHIO)1,3,4-THIADIAZOLE is used as an inhibitor for the virulence regulator, RegA, for the development of novel therapeutics targeting bacterial infections. Its ability to reduce the binding affinity of RegA for its DNA targets makes it a promising candidate for treating infections caused by bacteria that utilize RegA for virulence regulation.
Used in Research and Development:
In the field of microbiology and molecular biology, 2-AMINO-5-(4-CHLOROBENZYLTHIO)1,3,4-THIADIAZOLE is used as a research tool to study the role of RegA and its homologs in bacterial pathogenesis. 2-AMINO-5-(4-CHLOROBENZYLTHIO)1,3,4-THIADIAZOLE can help researchers understand the mechanisms of virulence regulation and develop strategies to combat bacterial infections.
Used in Veterinary Medicine:
2-AMINO-5-(4-CHLOROBENZYLTHIO)1,3,4-THIADIAZOLE is used as an antimicrobial agent in veterinary medicine, particularly for the treatment of Citrobacter rodentium infections in mice. Its effectiveness in reducing bacterial colonization when administered perorally makes it a potential candidate for the development of veterinary drugs targeting bacterial infections in animals.
Used in Drug Design and Development:
2-AMINO-5-(4-CHLOROBENZYLTHIO)1,3,4-THIADIAZOLE's interaction with the double helix-turn-helix (HTH) domain of RegA and its homologs can be utilized in the design and development of new drugs targeting bacterial infections. By understanding the molecular interactions between 2-AMINO-5-(4-CHLOROBENZYLTHIO)1,3,4-THIADIAZOLE and its target, researchers can develop more effective and specific inhibitors for bacterial virulence regulation.

Biochem/physiol Actions

Cell permeable: yes

InChI:InChI=1/C9H8ClN3S2/c10-7-3-1-6(2-4-7)5-14-9-13-12-8(11)15-9/h1-4H,5H2,(H2,11,12)

Upstream product

• 104-83-6 1-Chloro-4-(chloromethyl)benzene 
• 2349-67-9 2-Amino-5-mercapto-1,3,4-thiadiazole 
• 622-95-7 4-chlorobenzyl bromide 

Downstream Products

• 1408325-32-5 C₃₁H₃₆ClN₃OS₃ 
• 1431555-06-4 N-deacetyl-N-({5-[(4-chlorobenzyl)sulfanyl]-1,3,4-thiadiazol-2-yl}carbamoyl propionyl) N-methyl colchiceinamide 

Relevant academic research and scientific papers

Synthesis, characterization and biological evaluation of thiadiazole amide derivatives as nucleoside triphosphate diphosphohydrolases (NTPDases) inhibitors

Importance of extracellular nucleotides is widely understood. These nucleotides act as ligand for P2X and P2Y receptors and modulate a variety of biological functions. However, their extracellular concentration is maintained by a chain of enzymes termed as ecto-nucleotidases. Amongst them, nucleoside triphosphate diphosphohydrolases (NTPDases) is an important enzyme family responsible for the dephosphorylation of these nucleotides. Overexpression of NTPDases leads to many pathological conditions such as cancer and thrombosis. So far, only a few NTPDase inhibitors have been reported. Considering this scarcity of (NTPDase) inhibitors, a number of thiadiazole amide derivatives were synthesized and screened against human (h)-NTPDases. Several compounds showed promising inhibitory activity; compound 5a (IC50 (μM); 0.05 ± 0.008) and 5g (IC50 (μM); 0.04 ± 0.006) appeared to be the most distinguished molecules corresponding to h-NTPDase1 and -2. However, h-NTPDase3 was the least susceptible isozyme and only three compounds (5d, 5e, 5j) strongly inhibited h-NTPDase3. Interestingly, compound 5e was recognized as the most active compound that showed dual inhibition against h-NTPDase3 as well as against h-NTPDase8. For better comprehension of binding mode of these inhibitors, most potent inhibitors were docked with their respective isozyme.

Synthesis, carbonic anhydrase enzyme inhibition evaluations, and anticancer studies of sulfonamide based thiadiazole derivatives

The sulfonamide-based thiadiazole derivatives (STDs) with different hydrophobic/hydrophilic substitutions were synthesized to investigate their potentials in carbonic anhydrase inhibition (CAI). The CAI activity of the STDs (4a-4h) and the mechanism of the inhibition kinetics were determined. STD 4f contained both methoxy and Cl groups at benzene ring in STD 4f showed the lowest IC50 value. The molecular docking study confirmed that STDs bind strongly with the active sites of the target protein PDBID 1V9E. With the help of Lineweaver-Burk plots, inhibition kinetics of PDBIR 1V9E protein with STDs were determined. Cytotoxicity was checked against human keratinocyte cell lines and the anticancer properties were determined against MCF-7 cell lines. The electrochemical method was used to investigate the binding study with DNA and CA enzymes. Anticancer studies showed that STDs have weak bonding ability to DNA and strong binding ability with CA. It is concluded that anticancer activity is through CAI rather than by DNA binding.

COMPOUNDS HAVING PDE9A INHIBITORY ACTIVITY, AND PHARMACEUTICAL USES THEREOF

The present invention provides a compound having a specific chemical structure and having PDE9A inhibitory activity, or a pharmaceutically acceptable salt thereof. The present invention provides a composition containing the compound or a pharmaceutically acceptable salt thereof. The present invention provides a pharmaceutical use, for treating or preventing PDE9A-related diseases, of the compound according to the present invention, a salt thereof, and a composition containing the compound or salt. The present invention also provides a method for treating or preventing PDE9A-related diseases, the method comprising administering an effective amount of the compound according to the present invention, a salt thereof, or a composition containing the compound or salt to a subject in need of treatment.

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.

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.

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.

Containing 1, 3, 4 - thiadiazole thioether (sulfone) of 2 - (trifluoromethyl) benzamide derivatives, their preparation and use

The invention discloses a containing 1, 3, 4 - thiadiazole thioether (sulfone) of 2 - (trifluoromethyl) benzamide derivatives, their preparation and application, its general formula as follows, wherein: R1 Is methyl, ethyl, 2 - chloroethyl, 2 - fluoro ethyl, 2 - bromo ethyl, propyl, butyl, pentyl, 4 - cyano-benzyl, 4 - benzylic, 2 - fluorobenzyl, cyanomethyl, 2 - cyanoethyl, 3 - cyano-propyl, ; X is S or - S (O)2 -. The invention can control the south-knot nematode and rice [...], tobacco bacterial wilt and citrus canker composite infection.

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.

Identification of novel thiadiazoloacrylamide analogues as inhibitors of dengue-2 virus NS2B/NS3 protease

Dengue virus is endemic throughout tropical and subtropical regions, and cause severe epidemic diseases. The NS2B/NS3 protease is a promising drug target for dengue virus. Herein, we report the discovery and modification of a novel class of thiadiazoloacrylamide derivatives with potent inhibitory activity against the NS2B/NS3 protease. Thiadiazolopyrimidinone 1 was firstly determined as a new chemical structure against NS2B/NS3 from a commercial compound library. Then, we sought to identify similar compounds with the thiadiazoloacrylamide core that would exhibit better activity. A series of analogues were synthesized and fourteen of them were identified with strong inhibitory activities, in which the nitrile group in the linker part was discovered as an essential group for the inhibitory activity. The best of these (8b) demonstrated an IC50 at 2.24 μM based on in vitro DENV2 NS2B-NS3pro assays.