109925-12-4

Upstream product

• 2749-59-9 1,3-dimethyl-5-pyrazolone 
• 5203-77-0 1,3-dimethyl-1H-pyrazol-5-ol 
• 108-43-0 3-monochlorophenol 
• 27006-76-4 5-chloro-4-formyl-1,3-dimethylpyrazole 

Downstream Products

• 1424329-89-4 C₂₂H₂₃ClN₄O₂ 
• 446276-24-0 C₁₂H₁₁ClN₂O₃ 

Relevant academic research and scientific papers

Excellent antitumor and antimetastatic activities based on novel coumarin/pyrazole oxime hybrids

A series of hybrids 10a-v based on coumarin/pyrazole oxime have been synthesized, and exhibit good to excellent antitumor activities. Compound 10n has shown remarkable anticancer effect on SMMC-7721 cells (IC50 = 2.08 μM), which is considerably lower than 5-FU (IC50 = 37.8 μM) and similar to ADM (IC50 = 2.67 μM), with little effect on normal hepatic cells LO2. Notably, the suppression experiments of metastatic activities reveal that 10n also displays significant anti-metastasis effects through inhibiting cell migration and invasion in highly metastatic SMMC-7721 cell line, and dose-dependently reverses TGF-β1-induced epithelial-mesenchymal transition (EMT) procedure better than ADM. Finally, 10n also possesses low acute toxicity and potent tumor growth inhibitory property against SMMC-7721 cell lines in vivo. Our findings suggest that novel coumarin/pyrazole oxime hybrids are promising therapeutic agent candidates for further research.

Development of novel bis-pyrazole derivatives as antitumor agents with potent apoptosis induction effects and DNA damage

A series of bis-pyrazole derivatives were designed and synthesized, and their antitumor effects in vitro and in vivo were investigated. Several compounds displayed good antiproliferative activity with IC50 values in low-micromolar range against three human cancer cell lines in vitro, superior to 5-FU. The most potent compound 10M selectively inhibited human hepatocellular carcinoma cells but not non-tumor liver cell proliferation in vitro, and significantly triggered SMMC-7721 cell apoptosis by cleavage of both PARP and caspase-3 in a concentration-dependent manner. Further study revealed that the potent activity in the cell growth inhibition and apoptosis induction effects of 10M were related to DNA damage and activation of the p53 signaling pathway. Moreover, 10M showed low acute toxicity to mice and significant growth inhibition of the hepatoma tumor in vivo.

Synthesis and bioactivities of novel pyrazole oxime derivatives containing a 5-trifluoromethylpyridyl moiety

In this study, in order to find novel biologically active pyrazole oxime compounds, a series of pyrazole oxime derivatives containing a 5-trifluoromethylpyridyl moiety were synthesized. Preliminary bioassays indicated that most title compounds were found to display good to excellent acaricidal activity against Tetranychus cinnabarinus at a concentration of 200 μg/mL, and some designed compounds still showed excellent acaricidal activity against Tetranychus cinnabarinus at the concentration of 10 μg/mL, especially since the inhibition rates of compounds 8e, 8f, 8l, 8m, 8n, 8p, and 8q were all 100.00%. Interestingly, some target compounds exhibited moderate to good insecticidal activities against Plutella xylostella and Aphis craccivora at a concentration of 200 μg/mL; furthermore, compounds 8e and 8l possessed outstanding insecticidal activities against Plutella xylostella under the concentration of 50 μg/mL.

Synthesis and biological activities of novel 1,3,4-thiadiazole-containing pyrazole oxime derivatives

A new library of 1,3,4-thiadiazole-containing pyrazole oximes was designed and synthesized. Their acaricidal and insecticidal activities were evaluated. Bioassay results indicated that some target compounds exhibited good acaricidal and insecticidal properties. Especially, compound 8m had 80% acaricidal activity against Tetranychus cinnabarinus at the concentration of 50?μg/mL, compound 8f displayed 100% insecticidal activities against Aphis craccivora at the concentration of 50?μg/mL, compounds 8r and 8w showed 100% insecticidal activities against Plutella xylostella at the concentration of 50?μg/mL. Furthermore, compounds 8r (LC50?=?19.61?μg/mL) and 8w (LC50?=?9.78?μg/mL) possessed comparable or even better insecticidal activities than the control Pyridalyl (LC50?=?17.40?μg/mL) against P. xylostella.

Synthesis and evaluation of anticonvulsant activities of pyrazol semicarbazones. Part II

A series of 2-((5-aryloxy-1-methyl-3-methyl-1H-pyrazol-4-yl)methylene) hydrazinecarboxamides (6a-6l) and 2-((5-aryloxy-1-methyl-3-phenyl-1H-pyrazol-4-yl)methylene) hydrazinecarboxamides (7a-7l) were designed and synthesized. The maximal electroshock shock (MES) and subcutaneous pentylenetetrazole (sc-PTZ) seizure models in mice were used to evaluate the antiepileptic effect of compounds synthesized. Further, the acute neurotoxicity profile was also studied via the rotarod test. The results of sc-PTZ test indicate that a majority of compounds possessed anticonvulsant activity with long duration of protection effects. Among of them, compound 6k was found to be the most promising one, with an ED50 value of 20.4 mg/kg (in sc-PTZ model) and a PI value of 10.8, possessing higher anti-PTZ activity and wider safety margin than valproate and ethosuximide.

Discovery of 5-phenoxy-1,3-dimethyl-1H-pyrazole-4-carboxamides as potent agonists of TGR5 via sequential combinatorial libraries

Optimization of a high-throughput screening hit led to the discovery of a new series of 5-phenoxy-1,3-dimethyl-1H-pyrazole-4-carboxamides as highly potent agonists of TGR5. This novel chemotype was rapidly developed through iterative combinatorial library synthesis. It was determined that in vitro agonist potency correlated with functional activity data from human peripheral blood monocytes.