107518-49-0

Basic information

• Product Name: 2-(benzylthio)-5-methyl-[1,2,4]triazolo[1,5-a]pyrimidin-7(4H)-one
• Synonyms: 2-(benzylthio)-5-methyl-[1,2,4]triazolo[1,5-a]pyrimidin-7(4H)-one
• CAS NO: 107518-49-0
• Molecular Weight: 272.33
• Mol File: 107518-49-0.mol

Chemical Properties

• CAS DataBase Reference: 2-(benzylthio)-5-methyl-[1,2,4]triazolo[1,5-a]pyrimidin-7(4H)-one(CAS DataBase Reference)
• NIST Chemistry Reference: 2-(benzylthio)-5-methyl-[1,2,4]triazolo[1,5-a]pyrimidin-7(4H)-one(107518-49-0)
• EPA Substance Registry System: 2-(benzylthio)-5-methyl-[1,2,4]triazolo[1,5-a]pyrimidin-7(4H)-one(107518-49-0)

Safety Data

• Hazardous Substances Data: 107518-49-0(Hazardous Substances Data)

Upstream product

• 141-97-9 ethyl acetoacetate 
• 3922-47-2 3-amino-5-benzylthio<1,2,4>triazole 
• 3922-47-2 3-(benzylthio)-1H-1,2,4-triazol-5-amine 
• 100-44-7 benzyl chloride 

Downstream Products

• 51646-34-5 2-(benzylthio)-7-chloro-5-methyl-[1,2,4]triazolo[1,5-a]pyrimidine 
• 1383456-80-1 C₁₃H₁₃N₅S 
• 51646-39-0 2-benzylsulfanyl-5-methyl-7-morpholin-4-yl-[1,2,4]triazolo[1,5-a]pyrimidine 

Relevant articles and documents

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.

Design, synthesis and biological evaluation of [1,2,4]triazolo[1,5-a]pyrimidines as potent lysine specific demethylase 1 (LSD1/KDM1A) inhibitors

A new series of [1,2,4]triazolo[1,5-a]pyrimidine-based LSD1 inhibitors were designed, synthesized, and further evaluated for their cytotoxicity against MGC-803, EC109, A549 and PC-9 cells as well as the ability of inhibiting LSD1. Some of these compounds showed potent inhibition toward LSD1 and selectively inhibited growth of A549 and PC-9 cells. Compound 6l potently inhibited growth of PC-9 cells (IC50= 0.59 μM), about 4-fold more potent than 5-FU. Further SARs studies led to the identification of compounds 6l-m, which had good growth inhibition against all the tested cancer cell lines and were much more potent than 5-FU and GSK2879552. Besides, compounds 5p, 5q and 6i inhibited LSD1 potently (IC50= 0.154, 1.19 and 0.557 μM, respectively). Docking studies revealed that compound 5p formed arene-H interactions with Val333 and hydrogen bonds with surrounding Ala331, Met332, and Ala539 residues. Compound 5p significantly inhibited migration of A549 and PC-9 cells in a concentration-dependent manner, but had different effect on the expression of E-cadherin and N-cadherin. The [1,2,4]triazolo[1,5-a]pyrimidine scaffold may serve as a starting point for developing potent LSD1 inhibitors for cancer therapy.

Development of Highly Potent, Selective, and Cellular Active Triazolo[1,5- a]pyrimidine-Based Inhibitors Targeting the DCN1-UBC12 Protein-Protein Interaction

The cullin-RING ubiquitin ligases (CRLs) are responsible for about 20% of cellular protein degradation and regulate diverse cellular processes, and the dysfunction of CRLs is implicated in human diseases. Targeting the CRLs has become an emerging strategy for the treatment of human diseases. Herein, we describe the discovery of a hit compound from our in-house library and further structure-based optimizations, which have enabled the identification of new triazolo[1,5-a]pyrimidine-based inhibitors targeting the DCN1-UBC12 interaction. Compound WS-383 blocks the DCN1-UBC12 interaction (IC50 = 11 nM) reversibly and shows selectivity over selected kinases. WS-383 exhibits cellular target engagement to DCN1 in MGC-803 cells. WS-383 inhibits Cul3/1 neddylation selectively over other cullins and also induces accumulation of p21, p27, and NRF2. Collectively, targeting the DCN1-UBC12 interaction would be a viable strategy for selective neddylation inhibition of Cul3/1 and may be of therapeutic potential for disease treatment in which Cul3/1 is dysregulated.

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.

Applications of alkaloid essramycin and derivative thereof in resisting of plant viruses

The invention relates to applications of alkaloid essramycin and a derivative thereof in resisting of plant viruses, wherein the chemical structural formula of the alkaloid essramycin is represented in the specification, specifically the alkaloid essramyc

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 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.

Discovery, Structural Optimization, and Mode of Action of Essramycin Alkaloid and Its Derivatives as Anti-Tobacco Mosaic Virus and Anti-Phytopathogenic Fungus Agents

Plant diseases seriously affect crop yield and quality and are difficult to control. Marine natural products (MNPs) have become an important source of drug candidates with new biological mechanisms. Marine natural product essramycin (1) was found to have

Br?nsted Acid-Catalyzed Direct C(sp2)?H Heteroarylation Enabling the Synthesis of Structurally Diverse Biaryl Derivatives

Biaryl scaffold is an important class of structural frameworks that exists in many natural products and drug molecules. The development of transition metal-catalyzed approaches for the efficient construction of biaryl scaffolds has long been pursued because of the interesting structural features and broad biological profiles of biaryl scaffolds. Herein, we describe the Br?nsted acid-catalyzed direct C(sp2)?H heteroarylation that enables the synthesis of biaryl fragments (70 examples) in moderate to excellent yields (up to 99% yield), which was also performed at a gram scale and successfully applied to the privileged quinazoline scaffolds of the first-generation epidermal growth factor receptor (EGFR) inhibitors Gefitinib and Erlotinib, offering rapid access to a series of quinazoline-based biaryl compounds. Additionally, the late-stage diversifications were performed based on the compound 3 b, generating a library of structurally diverse and complex biaryl compounds. (Figure presented.).