3922-47-2

Usage

Uses

Used in Pharmaceutical Industry:
3-(Benzylsulfanyl)-1H-1,2,4-triazol-5-ylamine is used as an anti-tubercular agent for its potential to combat tuberculosis, a significant global health concern. Its unique structure and properties make it a promising candidate for the development of new drugs to treat this disease.
Used in Chemical Synthesis:
In the field of organic chemistry, 3-(Benzylsulfanyl)-1H-1,2,4-triazol-5-ylamine serves as a building block for the synthesis of other biologically active compounds. Its versatile chemical structure allows for the creation of a variety of molecules with potential applications in medicine and other fields.
Used in Corrosion Inhibition:
3-(Benzylsulfanyl)-1H-1,2,4-triazol-5-ylamine is used as a corrosion inhibitor in acidic environments. Its ability to protect materials from corrosion makes it valuable in industries where equipment is exposed to corrosive conditions, such as the oil and gas industry, and in the manufacturing of various industrial components.

InChI:InChI=1/C9H10N4S/c10-8-11-9(13-12-8)14-6-7-4-2-1-3-5-7/h1-5H,6H2,(H3,10,11,12,13)

Upstream product

• 31350-31-9 bis(benzylmercapto)methylene cyanamide 
• 100-39-0 benzyl bromide 
• 118025-46-0 3-amino-1H-1,2,4-triazole-5-thiol 
• 100-44-7 benzyl chloride 
• 16691-43-3 5-amino-3-mercapto-4H-[1,2,4]triazole 
• 16691-43-3 3-amino-5-thioxo-1,2,4-triazole 
• 16691-43-3 5-Amino-3-mercapto-1,2,4-triazole 

Downstream Products

• 133011-02-6 2-benzylthio-7-cyclopropyl-1,2,4-triazolo[1,5-a]pyrimidine 
• 98165-61-8 2-benzylthio-5-methyl-1,2,4-triazolo<1,5-a>pyrimidine 
• 98968-18-4 2-benzylthio-7-methyl-1,2,4-triazolo<1,5-a>pyrimidine 
• 98968-26-4 2-benzylthio-5,7-dihydroxy-1,2,4-triazolo<1,5-a>pyrimidine 
• 98968-14-0 2-benzylthio-6-chloro-1,2,4-triazolo[1,5-a]pyrimidine 
• 98968-15-1 2-benzylthio-1,2,4-triazolo[1,5-a]pyrimidine 
• 98982-95-7 2-benzylthio-6-chloro-7-hydroxy-5-methyl-1,2,4-triazolo<1,5-a>pyrimidine 
• 98968-41-3 2-benzylthio-5,7-bis-(trifluoromethyl)-1,2,4-triazolo[1,5-a]pyrimidine 
• 98968-42-4 2-benzylthio-5-methyl-7-trifluoromethyl-1,2,4-triazolo[1,5-a]-pyrimidine 
• 56347-23-0 2-benzylthio-5-methyl-7-phenyl-1,2,4-triazolo[1,5-a]pyrimidine 
• 876668-27-8 1-(2-benzylthio-7-methyl[1,2,4]triazolo[2,3-a]pyrimidin-6-yl)ethanone 

Relevant academic research and scientific papers

Synthesis and fungicidal activity of phenazine-1-carboxylic triazole derivatives

A total of 15 novel-substituted 3-(benzylsulfanyl)-1H-1,2,4-triazol-5-ylamine and 10 novel-substituted 3-benzylmercapto-1,2,4-triazol derivatives were synthesized based on the natural product phenazine-1-carboxylic acid (PCA). Their structures were confirmed by 1H-NMR, 13C-NMR, HRMS, and X-ray. Most substituted 3-benzylmercapto-1,2,4-triazol derivatives displayed very strong fungicidal activity against one or multiple plant pathogens in?vitro and in?vivo. Compounds 8b, 8h, and 8i showed a broad spectrum of fungicidal activity. Further field experiments indicated that compounds 8b, 8c, and 8h displayed better efficacy against rice blast (Pyricularia oryzae) than PCA. These data demonstrate that compounds 8b, 8c, and 8h are promising fungicidal candidates, deserving further studies. (Figure presented.).

Synthesis and evaluation of 1,2,4-triazolo[1,5- a ]pyrimidines as antibacterial agents against Enterococcus faecium

Rapid emergence of antibiotic resistance is one of the most challenging global public health concerns. In particular, vancomycin-resistant Enterococcus faecium infections have been increasing in frequency, representing 25% of enterococci infections in intensive care units. A novel class of 1,2,4-triazolo[1,5-a]pyrimidines active against E. faecium is reported herein. We used a three-component Biginelli-like heterocyclization reaction for the synthesis of a series of these derivatives based on reactions of aldehydes, β-dicarbonyl compounds, and 3-alkylthio-5-amino-1,2,4-triazoles. The resulting compounds were assayed for antimicrobial activity against the ESKAPE panel of bacteria, followed by investigation of their in vitro activities. These analyses identified a subset of 1,2,4-triazolo[1,5-a]pyrimidines that had good narrow-spectrum antibacterial activity against E. faecium and exhibited metabolic stability with low intrinsic clearance. Macromolecular synthesis assays revealed cell-wall biosynthesis as the target of these antibiotics.

Discovery of the Triazolo[1,5- a]Pyrimidine-Based Derivative WS-898 as a Highly Efficacious and Orally Bioavailable ABCB1 Inhibitor Capable of Overcoming Multidrug Resistance

Targeting P-glycoprotein (ABCB1 or P-gp) has been recognized as a promising strategy to overcome multidrug resistance. Here, we reported our medicinal chemistry efforts that led to the discovery of the triazolo[1,5-a]pyrimidine derivative WS-898 as a highly effective ABCB1 inhibitor capable of reversing paclitaxel (PTX) resistance in drug-resistant SW620/Ad300, KB-C2, and HEK293/ABCB1 cells (IC50 = 5.0, 3.67, and 3.68 nM, respectively), more potent than verapamil and zosuquidar. WS-898 inhibited the efflux function of ABCB1, thus leading to decreased efflux and increased intracellular PTX concentration in SW620/Ad300 cells. The cellular thermal shift assay indicated direct engagement of WS-898 to ABCB1. Furthermore, WS-898 stimulated the ATPase activity of ABCB1 but had minimal effects on cytochrome P450 3A4 (CYP3A4). Importantly, WS-898 increased PTX sensitization in vivo without obvious toxicity. The results suggest that WS-898 is a highly effective triazolo[1,5-a]pyrimidine-based ABCB1 inhibitor and shows promise in reversing ABCB1-mediated PTX resistance.

Drug repurposing: Discovery of troxipide analogs as potent antitumor agents

Drug repurposing plays a vital role in the discovery of undescribed bioactivities in clinical drugs. Based on drug repurposing strategy, we for the first time reported a novel series of troxipide analogs and then evaluated their antiproliferative activity against MCF-7, PC3, MGC-803, and PC9 cancer cell lines and WPMY-1, most of which showed obvious selectivity toward PC-3 over the other three cancer cell lines and WPMY-1. Compound 5q, especially, could effectively inhibit PC3 with an IC50 value of 0.91 μM, which exhibited around 53-fold selectivity toward WPMY-1. Data indicated that 5q effectively inhibited the colony formation, suppressed the cell migration, and induced G1/S phase arrest in PC3 cells. Also, compound 5q induced cell apoptosis by activating the two apoptotic signaling pathways in PC3 cells: death receptor-mediated extrinsic pathway and mitochondria-mediated intrinsic pathway. Compound 5q up-regulated the expression of both pro-apoptotic Bax and P53, while down-regulated anti-apoptotic Bcl-2 expression. Besides, compound 5q significantly increased the expression of cleaved caspase 3/9 and cleaved PARP. Therefore, the successful discovery of compound 5q may further validate the feasibility of this theory, which will encourage researchers to reveal undescribed bioactivities in traditional drugs.

Discovery of new [1,2,4] Triazolo[1,5-a]Pyrimidine derivatives that Kill gastric cancer cells via the mitochondria pathway

Mitochondria are known as “powerhouse of cells” and play the role of a bridge in redox balance, cell apoptosis, and autophagy. ROS accumulation can cause mitochondria damage, while the injured mitochondria will further enhance ROS levels reciprocally. Herein, we synthesized a novel series of [1,2,4]triazolo[1,5-a]pyrimidine-based compounds 4a-4v and tested their anti-proliferation efficacy against gastric cancer cell line MGC-803. Among them, compounds 4o and 4p inhibited gastric cancer cells at micromolar level. Compound 4o caused G2/M arrest and induced mitochondria-dependent apoptosis in MGC-803 and SGC-7901. However, inhibiting apoptosis pathway cannot prevent the inhibitory activity of compound 4o against gastric cancer cell. To our surprising, ROS level was increased by compound 4o and elevation of ROS could be rescued by NAC. In accordance with that, NAC absolutely prevented the anti-proliferation efficacy of compound 4o. We further found that autophagy inhibitor CQ rather than 3-MA partially reversed inhibitory activity of compound 4o in MGC-803 cells. Taken together, compound 4o exhibited its anti-proliferative activity via increasing ROS level and inducing autophagy, thus leading to apoptosis of gastric cancer cells. Therefore, compound 4o may support further development of lead compounds for gastric cancer therapy via mitochondria pathway.

Discovery of tofacitinib derivatives as orally active antitumor agents based on the scaffold hybridization strategy

In this work, a novel series of tofacitinib analogs were designed and synthesized based on the scaffold hybridization strategy and then evaluated for their antiproliferative activity toward three gastric cancer cell lines, leading to the identification of compound C18 which exhibited potent inhibitory activity against MGC-803 cell lines with an IC50 value of 2.68 μM. Compound C18 could effectively inhibit the colony formation, suppress the cell migration and induce apoptosis of MGC-803 cells through activating the p38 and JNK signaling pathways, while C18 showed no obvious effect on the cell cycle distribution in MGC-803 cells. In addition, C18 could initiate mitochondrial dysfunction of MGC-803 cells. Besides, in vivo antitumor studies indicated that C18 could inhibit gastric cancer tumor growth in vivo without obvious global toxicity.

Structure-Based Design, Synthesis, and Biological Evaluation of New Triazolo[1,5- a]Pyrimidine Derivatives as Highly Potent and Orally Active ABCB1 Modulators

ABCB1 is a promising therapeutic target for overcoming multidrug resistance (MDR). In this work, we reported the structure-based design of triazolo[1,5-a]pyrimidines as new ABCB1 modulators, of which WS-691 significantly increased sensitization of ABCB1-overexpressed SW620/Ad300 cells to paclitaxel (PTX) (IC50 = 22.02 nM). Mechanistic studies indicated that WS-691 significantly increased the intracellular concentration of PTX and [3H]-PTX while decreasing the efflux of [3H]-PTX in SW620/Ad300 cells by inhibiting the efflux function of ABCB1. The cellular thermal shift assay suggested that WS-691 could stabilize ABCB1 by directly binding to ABCB1. WS-691 could stimulate the activity of ABCB1 ATPase but had almost no inhibitory activity against CYP3A4. Importantly, WS-691 increased the sensitivity of SW620/Ad300 cells to PTX in vivo without observed toxicity. Collectively, WS-691 is a highly potent and orally active ABCB1 modulator capable of overcoming MDR. The triazolo[1,5-a]pyrimidine may be a promising scaffold for developing more potent ABCB1 modulators.

Experience-based discovery (EBD) of aryl hydrazines as new scaffolds for the development of LSD1/KDM1A inhibitors

Phenelzine was first employed to design new aryl hydrazine-based LSD1 inhibitors based on the experience-based discovery (EBD) strategy. Among these compounds, D8 potently inhibited LSD1 (IC50 = 882.30 nM) in a reversible manner. Compound D8 was selective to LSD1 over MAO-A/B and showed H3K4me2 competitive binding to LSD1. The interaction between H3K4me2 and LSD1 was also confirmed by the Co-IP assay. In LSD1 overexpressed A549 cells, compound D8 dose-dependently induced accumulation of LSD1 substrates H3K4me1/2 and H3K9me1/2, showed cellular target engagement to LSD1 and significantly inhibited cell migration of A549 cells. Docking studies suggested that compound D8 occupied the peptide binding region and therefore blocked the access of the peptide substrate to the FAD, finally leading to the demethylase activity inhibition of LSD1. The findings indicate that aryl hydrazines are new scaffolds for the design of LSD1 inhibitors, the identification of D8 provides further evidence for our previously proposed general principle that fused heterocycles with an amine group are potentially active toward LSD1 by competitive binding to LSD1 with H3 peptide substrates.

Synthesis, structure-activity relationship studies and biological characterization of new [1,2,4]triazolo[1,5-a]pyrimidine-based LSD1/KDM1A inhibitors

The histone lysine specific demethylase 1 (LSD1/KDM1A) is implicated in the development of cancers, targeting LSD1 has been recognized as a promising strategy for cancer therapy. To date, some small-molecule inhibitors are currently being investigated in clinical trials. Herein we report the design, synthesis and biochemical characterization of [1,2,4]triazolo[1,5-a]pyrimidine derivatives as new LSD1 inhibitors. Of these compounds, compound C26 inhibited LSD1 in a reversible manner (IC50 = 1.72 μM) and showed selectivity to LSD1 over MAO-A/B. Besides, compound C26 displayed FAD-competitive binding to LSD1. Interestingly, C26 did not inhibit horseradish peroxidase (HRP) and quench H2O2, thus excluding the possibility that LSD1 inhibition by C26 was due to the HRP inhibition and consumption of H2O2. In LSD1 overexpressed A549 cells, compound C26 concentration-dependently induced accumulation of H3K4me1/me2 and H3K9me2 and showed cellular target engagement to LSD1. Additionally, compound C26 significantly inhibited migration of A549 cells in a concentration-dependent manner, further western blot analysis showed that C26 increased expression levels of epithelial cell markers E-Cadherin and Claudin-1, down-regulated mesenchymal cell marker N-Cadherin and the upstream transcription factors Snail and Slug. Docking studies were also performed to rationalize the potency of C26 toward LSD1. To conclude, the [1,2,4]triazolo[1,5-a]pyrimidine could serve as a promising scaffold for the development of new LSD1 inhibitors.

Pyrimido-1,2,4-triazole compound and preparation method and application thereof

The present invention provides a pyrimido-1,2,4-triazole compound with a formula defined in the description, wherein a group R1 in the formula I represents an alkyl group or an aryl group, a group R2represents a hydrogen atom or a mercapto substituent group; a group R3 represents a hydrogen atom or alkyl. A preparation method and an application of the pyrimido-1,2,4-triazole compound are furtherprovided. The pyrimido-1,2,4-triazole compound has a structural unit of pyrimido-1,2,4-triazole. The compound can be used for LSD1-targeted anti-tumor drugs and opens up a new way for searching for novel LSD1-targeted anti-tumor drugs. In addition, the preparation method of the pyrimido-1,2,4-triazole compound provided is feasible, and the yield is high.