1355326-35-0

Basic information

• Product Name: N-cyclohexyl-2-(N-(3-fluorophenyl)-2-(2-Methyl-1H-iMidazol-1-yl)acetaMido)-2-(o-tolyl)acetaMide
• Synonyms: N-cyclohexyl-2-(N-(3-fluorophenyl)-2-(2-Methyl-1H-iMidazol-1-yl)acetaMido)-2-(o-tolyl)acetaMide;AGI5198;IDH-C35 /IDHC35;IDH C35;IDH-C35;N-[2-(Cyclohexylamino)-1-(2-methylphenyl)-2-oxoethyl]-N-(3-fluorophenyl)-2-methyl-1H-imidazole-1-acetamide;1H-Imidazole-1-acetamide, N-[2-(cyclohexylamino)-1-(2-methylphenyl)-2-oxoethyl]-N-(3-fluorophenyl)-2-methyl-;N-[2-(Cyclohexylamino)-1-(2-methylphenyl)-2-oxoethyl]-N-(3-fluorophenyl)-2-methyl-1H-imidazole-1-acetamide AGI 5198
• CAS NO: 1355326-35-0
• Molecular Formula: C₂₇H₃₁FN₄O₂
• Molecular Weight: 462.5590432
• EINECS: -0
• Product Categories: apis;Inhibitors
• Mol File: 1355326-35-0.mol
• Article Data: 3

Chemical Properties

• Boiling Point: 707.6±60.0 °C(Predicted)
• Appearance: white to beige/
• Density: 1.21±0.1 g/cm3(Predicted)
• Storage Temp.: 2-8°C
• Solubility: DMSO: soluble3mg/mL, clear
• PKA: 14.02±0.20(Predicted)
• Stability: Stable for 1 year from date of purchase as supplied. Solutions in DMSO or ethanol may be stored at -20°C for up to 3 months.
• CAS DataBase Reference: N-cyclohexyl-2-(N-(3-fluorophenyl)-2-(2-Methyl-1H-iMidazol-1-yl)acetaMido)-2-(o-tolyl)acetaMide(CAS DataBase Reference)
• NIST Chemistry Reference: N-cyclohexyl-2-(N-(3-fluorophenyl)-2-(2-Methyl-1H-iMidazol-1-yl)acetaMido)-2-(o-tolyl)acetaMide(1355326-35-0)
• EPA Substance Registry System: N-cyclohexyl-2-(N-(3-fluorophenyl)-2-(2-Methyl-1H-iMidazol-1-yl)acetaMido)-2-(o-tolyl)acetaMide(1355326-35-0)

Safety Data

• Hazard Codes: T
• Statements: 25
• Safety Statements: 45
• RIDADR: UN 2811 6.1 / PGIII
• WGK Germany: 3
• Hazardous Substances Data: 1355326-35-0(Hazardous Substances Data)

Usage

Description

N-Cyclohexyl-2-(N-(3-fluorophenyl)-2-(2-methyl-1H-imidazol-1-yl)acetamido)-2-(o-tolyl)acetamide is a complex organic compound with a unique molecular structure. It is characterized by its cyclohexyl, fluorophenyl, and imidazol-1-yl groups, which contribute to its potential applications in various fields.

Uses

Used in Pharmaceutical Industry:
N-Cyclohexyl-2-(N-(3-fluorophenyl)-2-(2-methyl-1H-imidazol-1-yl)acetamido)-2-(o-tolyl)acetamide is used as a potential therapeutic agent for targeting specific protein interactions in the treatment of various diseases, including cancer. Its unique molecular structure allows for the modulation of protein functions, making it a promising candidate for drug development.
Used in Chemical Research:
N-Cyclohexyl-2-(N-(3-fluorophenyl)-2-(2-methyl-1H-imidazol-1-yl)acetamido)-2-(o-tolyl)acetamide is also used as a research tool in the field of chemistry, particularly in the study of protein-ligand interactions and the development of novel inhibitors. Its structural features enable researchers to investigate the binding properties and potential applications of similar compounds in various biological systems.
Used in Drug Design:
N-Cyclohexyl-2-(N-(3-fluorophenyl)-2-(2-methyl-1H-imidazol-1-yl)acetamido)-2-(o-tolyl)acetamide serves as a valuable starting point for the design of new drugs targeting specific biological pathways. Its structural diversity and potential for modification make it an attractive candidate for the development of targeted therapies.

Biochem/physiol Actions

In human chondrosarcoma cell line JJ012, AGI-5198 promotes apoptosis and G2/M cell cycle arrest. It also prevents the generation of colony in chondrosarcoma cell lines. AGI-5198 hinders the multiplication of cell and induces demethylation of H3K9me3 and H3K27me3.

References

1) Popovici-Muller?et al. (2012),?Discovery of the First Potent Inhibitors of Mutant IDH1 That Lower Tumor 2-HG In Vivo; ACS Med. Chem. Lett.,?3?850 2) Rohle?et al. (2013),?An inhibitor of mutant IDH1 delays growth and promotes differentiation of glioma cells; Science,?340?626

Upstream product

• 529-20-4 2-methylphenyl aldehyde 
• 372-19-0 meta-fluoroaniline 
• 693-98-1 2-methylimidazole 
• 1355324-97-8 2-chloro-N-(2-(cyclohexylamino)-2-oxo-1-(o-tolyl)ethyl)-N-(3-fluorophenyl)acetamide 

Downstream Products

• 1355326-36-1 N-cyclohexyl-2-(N-(3-fluorophenyl)-2-(2-methyl-1H-imidazol-1-yl)acetamido)-2-(o-tolyl)acetamide hydrochloric acid 

Relevant articles and documents

Synthesis and evaluation of radiolabeled AGI-5198 analogues as candidate radiotracers for imaging mutant IDH1 expression in tumors

Mutations in the metabolic enzyme isocitrate dehydrogenase 1 (IDH1) are commonly found in gliomas. AGI-5198, a potent and selective inhibitor of the mutant IDH1 enzyme, was radiolabeled with radioiodine and fluorine-18. These radiotracers were evaluated as potential probes for imaging mutant IDH1 expression in tumors with positron emission tomography (PET). Radioiodination of AGI-5198 was achieved using a tin precursor in 79 ± 6% yield (n = 9), and 18F-labeling was accomplished by the Ugi reaction in a decay-corrected radiochemical yield of 2.6 ± 1.6% (n = 5). The inhibitory potency of the analogous nonradioactive compounds against mutant IDH1 (IDH1-R132H) was determined in enzymatic assays. Cell uptake studies using radiolabeled AGI-5198 analogues revealed somewhat higher uptake in IDH1-mutated cells than that in wild-type IDH1 cells. The radiolabeled compounds displayed favorable tissue distribution characteristics in vivo, and good initial uptake in IDH1-mutated tumor xenografts; however, tumor uptake decreased with time. Radioiodinated AGI-5198 exhibited higher tumor-to-background ratios compared with 18F-labeled AGI-5198; unfortunately, similar results were observed in wild-type IDH1 tumor xenografts as well, indicating lack of selectivity for mutant IDH1 for this tracer. These results suggest that AGI-5198 analogues are not a promising platform for radiotracer development. Nonetheless, insights gained from this study may help in design and optimization of novel chemical scaffolds for developing radiotracers for imaging the mutant IDH1 enzyme.

Discovery of the first potent inhibitors of mutant IDH1 that lower tumor 2-HG in vivo

Optimization of a series of R132H IDH1 inhibitors from a high throughput screen led to the first potent molecules that show robust tumor 2-HG inhibition in a xenograft model. Compound 35 shows good potency in the U87 R132H cell based assay and ～90% tumor 2-HG inhibition in the corresponding mouse xenograft model following BID dosing. The magnitude and duration of tumor 2-HG inhibition correlates with free plasma concentration.