Month: November 2022

Moderhack, Dietrich published the artcilePhenylcarbamoylation of N-acetyl-1,2,4-triazolium-4-aminides revisited, Recommanded Product: 4-Amino-1-methyl-4H-1,2,4-triazol-1-ium iodide, the main research area is phenylcarbamoylation acetyltriazolium aminide.

The reaction of N-acetyl-1,2,4-triazolium-4-aminides with PhSCN affords ring functionalized products rather than linear adducts. Analogous compounds are obtained from 1-acetamido-4-methyl-4H-1,2,4-triazolium iodide and its imidazolium congener. Twofold carbamoylation occurs on reaction of aminotriazolium salts in the presence of base. Azoliums having Me at C(5)/(2) are inert throughout.

Heterocycles published new progress about Carbamoylation. 39602-93-2 belongs to class triazoles, name is 4-Amino-1-methyl-4H-1,2,4-triazol-1-ium iodide, and the molecular formula is C3H7IN4, Recommanded Product: 4-Amino-1-methyl-4H-1,2,4-triazol-1-ium iodide.

Referemce:
1,2,3-Triazole – Wikipedia,
Triazoles – an overview | ScienceDirect Topics

Savateev, Aleksandr published the artcileHalogen free 1,2,3- and 1,2,4-triazolide based ionic liquids: synthesis and properties, Category: triazoles, the main research area is azolium triazolide ionic liquid preparation thermal stability dynamic viscosity.

Triazoles were successfully used as building blocks to create “”fully organic”” ILs featuring on both sides organic ions, i.e., 1,2,3- or 1,2,4-triazolide anions and 1,2,4-triazolium or imidazolium cations. Glass transition temperatures, densities and viscosities of these ILs were determined Their electrochem. and thermal stability and also conductivity, were higher than those for known ILs.

Chemical Communications (Cambridge, United Kingdom) published new progress about Current density. 39602-93-2 belongs to class triazoles, name is 4-Amino-1-methyl-4H-1,2,4-triazol-1-ium iodide, and the molecular formula is C3H7IN4, Category: triazoles.

Referemce:
1,2,3-Triazole – Wikipedia,
Triazoles – an overview | ScienceDirect Topics

Kawaguchi, Mitsuyasu published the artcileDevelopment of an ENPP1 Fluorescence Probe for Inhibitor Screening, Cellular Imaging, and Prognostic Assessment of Malignant Breast Cancer, Name: 7-Chloro-5-methyl-[1,2,4]triazolo[1,5-a]pyrimidine, the main research area is ENPP1 fluorescence probe inhibitor screening imaging prognostic breast cancer.

Ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) is a type II transmembrane glycoprotein that is involved in bone metabolism and insulin resistance, hydrolyzes 2′,3′-cGAMP (a STING ligand that promotes innate immunity), and is associated with cancer stemness in breast cancers and glioblastoma. Therefore, ENPP1 is considered a candidate therapeutic target and/or biomarker for early diagnosis of malignant tumors. In this study, we designed and synthesized a sensitive ENPP1 fluorescence probe, Tokyo Green (TG) mAMP. We used it to screen a chem. library for non-phosphate ENPP1 inhibitors. Structural optimization of a selected hit afforded a potent and specific ENPP1 inhibitor. We further found that ENPP1 mRNA expression in tissue samples from patients with triple-neg. breast cancer was significantly inversely related to recurrence-free survival (RFS) and overall survival (OS), and TG-mAMP assay revealed a significant difference in ENPP1 activity between ENPP1 high-expressing and ENPP1 low-expressing samples. Our results suggest that TG-mAMP assay might be a rapid and inexpensive tool for predicting the prognosis of patients with malignant breast cancers.

Journal of Medicinal Chemistry published new progress about Cancer diagnosis. 24415-66-5 belongs to class triazoles, name is 7-Chloro-5-methyl-[1,2,4]triazolo[1,5-a]pyrimidine, and the molecular formula is C6H5ClN4, Name: 7-Chloro-5-methyl-[1,2,4]triazolo[1,5-a]pyrimidine.

Referemce:
1,2,3-Triazole – Wikipedia,
Triazoles – an overview | ScienceDirect Topics

Maekawa, Kazuyuki published the artcileControl of seedling growth by pseudopurine and pyrimidine derivatives, Synthetic Route of 24415-66-5, the main research area is pseudopurine pyrimidine seedling growth.

The effects of ∼60 pseudopurine and guanidinopyrimidine derivatives on rice, radish, barnyard grass, and Atriplex gmelinii seedling growth were reported. Thus, I [35186-71-1] and II [37140-02-6] strongly inhibited rice seedling root growth. Some thiadiazolo[3,2-a]pyrimidine derivatives repressed leaves and stalks. III [56347-19-4] and IV [51646-15-2] and alkanesulfinyl derivatives of thiadiazolo[3,2-a]pyrimidine markedly inhibited barnyard grass but not rice. On the other hand V [275-02-5] and VI [16018-49-8] inhibited only radish germination.

Journal of the Faculty of Agriculture, Kyushu University published new progress about Atriplex gmelini. 24415-66-5 belongs to class triazoles, name is 7-Chloro-5-methyl-[1,2,4]triazolo[1,5-a]pyrimidine, and the molecular formula is C6H5ClN4, Synthetic Route of 24415-66-5.

Referemce:
1,2,3-Triazole – Wikipedia,
Triazoles – an overview | ScienceDirect Topics

Zhang, Qian published the artcileDiscovery of Triazolo-pyridazine/-pyrimidine Derivatives Bearing Aromatic (Heterocycle)-Coupled Azole Units as Class II c-Met Inhibitors, SDS of cas: 24415-66-5, the main research area is triazolopyridazine triazolopyrimidine preparation cMet kinase inhibition SAR anticancer human.

Two series of novel triazolo-pyridazine/-pyrimidine derivatives were designed, synthesized, and evaluated for their inhibitory activity against c-Met kinase, as well as three c-Met overexpressed cancer cell lines (A549, MCF-7, and HeLa) and one normal human hepatocytes cell line LO2 in vitro. The most promising compound I exhibited significant cytotoxicity against A549, MCF-7, and HeLa cell lines with IC50 values of 1.06 +/- 0.16, 1.23 +/- 0.18, and 2.73 +/- 0.33μM, resp. Moreover, the inhibitory activity of compound I against c-Met kinase (IC50 = 0.090μM) was equal to that of Foretinib (IC50 = 0.019μM). The result of the acridine orange single staining test demonstrated that compound I could remarkably induce apoptosis of A549 cells. The results of apoptosis and cycle distribution of cells showed that compound I could induce late apoptosis of A549 cells and stimulate A549 cells arresting in the G0/G1 phase. Structure-activity relationships (SARs), pharmacol. results, and docking studies indicated that the introduction of 5-methylthiazole fragment to the five-atom moiety was beneficial for the activity. So far, the existing data indicated that I may become a potential class II c-Met inhibitor.

ACS Omega published new progress about Antitumor agents. 24415-66-5 belongs to class triazoles, name is 7-Chloro-5-methyl-[1,2,4]triazolo[1,5-a]pyrimidine, and the molecular formula is C6H5ClN4, SDS of cas: 24415-66-5.

Referemce:
1,2,3-Triazole – Wikipedia,
Triazoles – an overview | ScienceDirect Topics

Li, Zhong-Rui published the artcileExperience-based discovery (EBD) of aryl hydrazines as new scaffolds for the development of LSD1/KDM1A inhibitors, Category: triazoles, the main research area is LSD1 inhibitor experience discovery aryl hydrazine scaffolds; Aryl hydrazines; Epigenetic regulation; Experience-based discovery; LSD1 inhibitors; [1, 2, 4] triazolo[1, 5- a] pyrimidine.

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.

European Journal of Medicinal Chemistry published new progress about Antitumor agents. 24415-66-5 belongs to class triazoles, name is 7-Chloro-5-methyl-[1,2,4]triazolo[1,5-a]pyrimidine, and the molecular formula is C6H5ClN4, Category: triazoles.

Referemce:
1,2,3-Triazole – Wikipedia,
Triazoles – an overview | ScienceDirect Topics

Sanchez, Robert M. published the artcileSynthesis and structure-activity relationships of 1,2,4-triazolo[1,5-a]pyrimidin-7(3H)-ones as novel series of potent β isoform selective phosphatidylinositol 3-kinase inhibitors, Application In Synthesis of 502546-41-0, the main research area is triazolo pyrimidinone preparation phosphatidylinositol 3 kinase inhibitor anticancer SAR.

A series of 1,2,4-triazolo[1,5-a]pyrimidin-7(3H)-ones with excellent enzyme inhibition, improved isoform selectivity, and excellent inhibition of downstream phosphorylation of AKT has been identified. Several compounds in the series demonstrated potent (∼ 0.100 μM IC50) growth inhibition in a PTEN deficient cancer cell line.

Bioorganic & Medicinal Chemistry Letters published new progress about Antitumor agents. 502546-41-0 belongs to class triazoles, name is 5-Cyclopropyl-4H-1,2,4-triazol-3-amine, and the molecular formula is C5H8N4, Application In Synthesis of 502546-41-0.

Referemce:
1,2,3-Triazole – Wikipedia,
Triazoles – an overview | ScienceDirect Topics

Wang, Shuai published the artcileDevelopment of Highly Potent, Selective, and Cellular Active Triazolo[1,5-a]pyrimidine-Based Inhibitors Targeting the DCN1-UBC12 Protein-Protein Interaction, Synthetic Route of 24415-66-5, the main research area is triazolo pyrimidine derivative preparation DCN1 UBC12 protein interaction cancer.

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 inhouse 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.

Journal of Medicinal Chemistry published new progress about Antitumor agents. 24415-66-5 belongs to class triazoles, name is 7-Chloro-5-methyl-[1,2,4]triazolo[1,5-a]pyrimidine, and the molecular formula is C6H5ClN4, Synthetic Route of 24415-66-5.

Referemce:
1,2,3-Triazole – Wikipedia,
Triazoles – an overview | ScienceDirect Topics

Wang, Shuai published the artcileSynthesis, structure-activity relationship studies and biological characterization of new [1,2,4]triazolo[1,5-a]pyrimidine-based LSD1/KDM1A inhibitors, SDS of cas: 24415-66-5, the main research area is triazolopyrimidine preparation SAR LSD1 KDM1A inhibitor anticancer activity; Antiproliferative activity; LSD1 inhibitors; Migration inhibition; [1,2,4]triazolo[1,5-a]pyrimidines.

The design, synthesis and biochem. characterization of [1,2,4]triazolo[1,5-a]pyrimidine derivatives I [R1 = H, [(2-bromophenyl)methyl]sulfanyl, prop-2-en-1-ylsulfanyl, [(1H-1,3-benzodiazol-2-ylmethyl)sulfanyl], etc.; R2 = H, Me, (CH2)4CH3; R3 = Me, Et, C6H5; R2, R3 = -(CH2)3-; R4 = H, C6H5, [4-(4-methylpiperazin-1-yl)phenyl], etc.] as new LSD1 inhibitors have been reported. Of these compounds, compound I [R1 = (1H-1,3-benzodiazol-2-ylsulfanyl)methyl; R2 = H; R3 = Me; R4 = [4-(4-methylpiperazin-1-yl)phenyl]] (II) inhibited LSD1 in a reversible manner (IC50 = 1.72 μM) and showed selectivity to LSD1 over MAO-A/B. Besides, compound II displayed FAD-competitive binding to LSD1. Interestingly, compound II did not inhibit horseradish peroxidase (HRP) and quench H2O2, thus excluding the possibility that LSD1 inhibition by compound II was due to the HRP inhibition and consumption of H2O2. In LSD1 overexpressed A549 cells, compound II concentration-dependently induced accumulation of H3K4me1/me2 and H3K9me2 and showed cellular target engagement to LSD1. Addnl., compound II significantly inhibited migration of A549 cells in a concentration-dependent manner, further western blot anal. showed that compound II 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 compound II toward LSD1. To conclude, the [1,2,4]triazolo[1,5-a]pyrimidine I could serve as a promising scaffold for the development of new LSD1 inhibitors.

European Journal of Medicinal Chemistry published new progress about Antitumor agents. 24415-66-5 belongs to class triazoles, name is 7-Chloro-5-methyl-[1,2,4]triazolo[1,5-a]pyrimidine, and the molecular formula is C6H5ClN4, SDS of cas: 24415-66-5.

Referemce:
1,2,3-Triazole – Wikipedia,
Triazoles – an overview | ScienceDirect Topics

Wang, Shuai published the artcileDiscovery of new [1,2,4] Triazolo[1,5-a]Pyrimidine derivatives that Kill gastric cancer cells via the mitochondria pathway, Synthetic Route of 24415-66-5, the main research area is triazolopyrimidinylamino diarylpropenone preparation antitumor activity SAR; 1,2,4]triazolo[1,5-a]pyrimidines; Apoptosis; Autophagy; Gastric cancer; Mitochondrial pathway.

A novel series of [1,2,4]triazolo[1,5-a]pyrimidine-based compoundsI [R1 = benzyl, 4-fluorobenzyl, 4-chlorobenzyl, etc.; R2 = Me, Et, Ph; R3 = H, Me] and II [R4 = Ph, (4-(3-(6-bromo-2-pyridyl)prop-2-enoyl)phenyl), (4-(3-(5-bromo-2-pyridyl)prop-2-enoyl)phenyl), etc.] were synthesized and tested their anti-proliferation efficacy against gastric cancer cell line MGC-803. Among them, compounds II [R4 = (4-(3-(6-bromo-2-pyridyl)prop-2-enoyl)phenyl), (4-(3-(5-bromo-2-pyridyl)prop-2-enoyl)phenyl)] inhibited gastric cancer cells at micromolar level. Compound II [R4 = (4-(3-(6-bromo-2-pyridyl)prop-2-enoyl)phenyl)] 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 II [R4 = (4-(3-(6-bromo-2-pyridyl)prop-2-enoyl)phenyl)] against gastric cancer cell. To our surprising, ROS level was increased by compound II [R4 = (4-(3-(6-bromo-2-pyridyl)prop-2-enoyl)phenyl)] 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 II [R4 = (4-(3-(6-bromo-2-pyridyl)prop-2-enoyl)phenyl)] in MGC-803 cells. Taken together, compound II [R4 = (4-(3-(6-bromo-2-pyridyl)prop-2-enoyl)phenyl)] exhibited its anti-proliferative activity via increasing ROS level and inducing autophagy, thus leading to apoptosis of gastric cancer cells. Therefore, compound II [R4 = (4-(3-(6-bromo-2-pyridyl)prop-2-enoyl)phenyl)] may support further development of lead compounds for gastric cancer therapy via mitochondria pathway.

European Journal of Medicinal Chemistry published new progress about Antitumor agents. 24415-66-5 belongs to class triazoles, name is 7-Chloro-5-methyl-[1,2,4]triazolo[1,5-a]pyrimidine, and the molecular formula is C6H5ClN4, Synthetic Route of 24415-66-5.

Referemce:
1,2,3-Triazole – Wikipedia,
Triazoles – an overview | ScienceDirect Topics