1308400-19-2

Upstream product

• 109-01-3 1-methyl-piperazine 
• 70261-82-4 4-[(4-methyl-1-piperazinyl)methyl]aniline 
• 5334-40-7 4-nitro-1H-pyrazole-3-carboxylic acid 

Downstream Products

• 1308400-20-5 4-amino-N-[4-[(4-methylpiperazin-1-yl) methyl] phenyl]-1Hpyrazole-3-carboxamide 
• 1308400-21-6 5-(3-cyclopropylureido)-N-[4-[(4-methylpiperazinyl)-methyl] phenyl]-1H-pyrazole-3-carboxamide 
• 1308400-39-6 C₂₃H₂₆N₆O₂ 
• 1308400-35-2 C₂₂H₂₇N₇O 
• 1429515-59-2 4-((7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino)-N-(4-((4-methylpiperazin-1-yl)methyl)phenyl)-1H-pyrazole-3-carboxamide 

Relevant academic research and scientific papers

(4 - Fused heterocycle-substituted amino)-3 - 1H-pyrazolecarboxamide compound and application thereof

The invention relates to the field of pharmaceutical chemistry and in particular relates to 4-(fused-heterocycle substituted amino)-1H-pyrazol-3-formamide compounds and application thereof, preparation methods of the compounds, pharmaceutical compositions

4-(saturated aliphatic ring-pyrimidine/pyridine substituted)amino-1H-3-pyrazol carboxamide FMS-like tyrosine kinase 3 (FLT3) inhibitor and application thereof

The invention relates to 4-(saturated aliphatic ring-pyrimidine/pyridine substituted)amino-1H-3-pyrazol carboxamide FMS-like tyrosine kinase 3 (FLT3) inhibitor, an application thereof, or pharmaceutically acceptable salt, solvate, isomer, ester, acid, met

Discovery of 4-((7H-Pyrrolo[2,3-d]pyrimidin-4-yl)amino)-N-(4-((4-methylpiperazin-1-yl)methyl)phenyl)-1H-pyrazole-3-carboxamide (FN-1501), an FLT3- and CDK-Kinase Inhibitor with Potentially High Efficiency against Acute Myelocytic Leukemia

A series of 1-H-pyrazole-3-carboxamide derivatives have been designed and synthesized that exhibit excellent FLT3 and CDK inhibition and antiproliferative activities. A structure-activity-relationship study illustrates that the incorporation of a pyrimidine-fused heterocycle at position 4 of the pyrazole is critical for FLT3 and CDK inhibition. Compound 50 (FN-1501), which possesses potent inhibitory activities against FLT3, CDK2, CDK4, and CDK6 with IC50 values in the nanomolar range, shows antiproliferative activities against MV4-11 cells (IC50: 0.008 μM), which correlates with the suppression of retinoblastoma phosphorylation, FLT3, ERK, AKT, and STAT5 and the onset of apoptosis. Acute-toxicity studies in mice show that compound 50 (LD50: 186 mg/kg) is safer than AT7519 (32 mg/kg). In MV4-11 xenografts in a nude-mouse model, compound 50 can induce tumor regression at the dose of 15 mg/kg, which is more efficient than cytarabine (50 mg/kg). Taken together, these results demonstrate the potential of this unique compound for further development into a drug applied in acute-myeloid-leukemia (AML) therapeutics.

Discovery of the selective and efficacious inhibitors of FLT3 mutations

Fms-like tyrosine kinase 3 (FLT3) is among the most frequently mutated protein in acute myeloid leukemia (AML), which has been confirmed as an important drug target for AML chemotherapy. Starting from the lead compound LT-106-175, a series of 1-H-pyrazole-3-carboxamide derivatives were synthesized to improve the FLT3 inhibitory potency and selectivity. Among them, compound 50 was identified as a highly potent and selective FLT3 inhibitor (IC50 = 0.213 nM), which showed equal activities against various mutants of FLT3 including FLT3 (ITD)-D835V and FLT3 (ITD)-F691L that is resistant to quizartinib. Compound 50 also exhibited efficacy against the human AML cell line MV4-11 (IC50 = 16.1 nM) harboring FLT3-ITD mutants. Inversely, compound 50 displayed no cytotoxicity to FLT3-independent cells, and the biochemical analyses showed that its effects were related to the inhibition of FLT3 signal pathways. Additionally, compound 50 induced apoptosis in MV4-11 cell as demonstrated by flow cytometry. Moreover, compound 50 showed enhanced metabolic stability. Altogether, it was concluded that compound 50 could be a promising FLT3 inhibitor for further developing therapeutic remedy of AML.

4-(aromatic heterocyclic substituted)amino-1H-3-pyrazolecarboxamide FLT3 (Fms-like tyrosine kinase) inhibitor and application thereof

The invention relates to a novel 4-(aromatic heterocyclic substituted)amino-1H-3-pyrazolecarboxamide compound or pharmaceutically acceptable salts, solvates, isomers, esters, acids, metabolites or pro-drugs thereof and a preparation method thereof. The in

POLYCYCLIC SUBSTITUTED PYRAZOLE KINASE ACTIVITY INHIBITORS AND USE THEREOF

The present invention relates to the field of medicinal chemistry, and in particular relates to 4-(five-membered heterocyclic pyrimidine/pyridine substituted) amino-1H-3-pyrazolecarboxamide derivatives, the preparation method thereof, pharmaceutical compo

Novel 1H-pyrazole-3-carboxamide derivatives: Synthesis, anticancer evaluation and identification of their DNA-binding interaction

Four novel 1H-pyrazole-3-carboxamide derivatives were synthesized, and their antiproliferative effect on cancer cells, kinase inhibition, and in particular, the DNA-binding interaction were investigated to interpret the antitumor mechanisms. A DNA minor g