89060-39-9

Upstream product

• 89060-23-1 <3-Phenyl-1-(p-tolyl)-1,2,4-triazol-5-yl>methanol 
• 539-44-6 N-4-methylphenylhydrazine 
• 100-52-7 benzaldehyde 
• 1858-99-7 benzaldehyde p-tolylhydrazone 
• 30216-01-4 2-phenyl-2-oxazolin-4-one 

Downstream Products

• 89060-52-6 3-Phenyl-1-(p-tolyl)-1,2,4-triazol-5-carbonsaeure<<3-phenyl-1-(p-tolyl)-1,2,4-triazol-5-yl>methyl>ester 
• 89060-54-8 Kalium-<3-phenyl-1-(p-tolyl)-1,2,4-triazol-5-carboxylat> 

Relevant academic research and scientific papers

Identification of novel 1,3-diaryl-1,2,4-triazole-capped histone deacetylase 6 inhibitors with potential anti-gastric cancer activity

Histone deacetylase 6 (HDAC6) has emerged as a critical regulator of many cellular pathways in tumors due to its unique structure basis and abundant substrate types. Over the past few decades, the role played by HDAC6 inhibitors as anticancer agents has sparked great interest of biochemists worldwide. However, they were less reported for gastric cancer therapy. In this paper, with the help of bioisosteric replacement, in-house library screening, and lead optimization strategies, we designed, synthesized and verified a series of 1,3-diaryl-1,2,4-triazole-capped HDAC6 inhibitors with promising anti-gastric cancer activities. Amongst, compound 9r displayed the best inhibitory activity towards HDAC6 (IC50 = 30.6 nM), with 128-fold selectivity over HDAC1. Further BLI and CETSA assay proved the high affinity of 9r to HDAC6. In addition, 9r could dose-dependently upregulate the levels of acetylated α-tubulin, without significant effect on acetylated histone H3 in MGC803 cells. Besides, 9r exhibited potent antiproliferative effect on MGC803 cells, and promoted apoptosis and suppressed the metastasis without obvious toxicity, suggesting 9r would serve as a potential lead compound for the development of novel therapeutic agents of gastric cancer.

Discovery of pyrazole derivatives as cellular active inhibitors of histone lysine specific demethylase 5B (KDM5B/JARID1B)

KDM5B (also known as PLU-1 and JARID1B) is 2-oxoglutarate and Fe2+ dependent oxygenase that acts as a histone H3K4 demethylase, which is a key participant in inhibiting the expression of tumor suppressors as a drug target. Here, we present the discovery of pyrazole derivatives compound 5 by structure-based virtual screening and biochemical screening with IC50 of 9.320 μM against KDM5B, and its subsequent optimization to give 1-(4-methoxyphenyl)-N-(2-methyl-2-morpholinopropyl)-3-phenyl-1H-pyrazole-4-carboxamide (27 ab), a potent KDM5B inhibitor with IC50 of 0.0244 μM. In MKN45 cells, compound 27 ab can bind and stabilize KDM5B and induce the accumulation of H3K4me2/3, bona fide substrates of KDM5B, while keep the amount of H3K4me1, H3K9me2/3 and H3K27me2 without change. Further biological study also indicated that compound 27 ab is a potent cellular active KDM5B inhibitor that can inhibit MKN45 cell proliferation, wound healing and migration. In sum, our finding gives a novel structure for the discovery of KDM5B inhibitor and targeting KDM5B may be a new therapeutic strategy for gastric cancer treatment.

3-Phenyl-1,2,4-triazole-5-carbaldehydes Substituted in Position 1

The aldehydes 7 - first examples of the yet unknown class of 1,2,4-triazole-5-carbaldehydes substituted in position 1 - can be obtained in excellent yield by lead tetraacetate oxidation of 2; the Kroehnke reaction with 5 provides an alternative route.Due