CTX0294885 Chemical Properties

Density 

1.332±0.06 g/cm3(Predicted)

storage temp. 

Store at -20°C

solubility 

≥21.9 mg/mL in DMSO; insoluble in EtOH; insoluble in H2O

form 

solid

pka

14.57±0.46(Predicted)

color 

Light yellow to green yellow

InChIKey

FCLOIQHNUARDSR-UHFFFAOYSA-N

SMILES

C(NC)(=O)C1=CC=CC=C1NC1C(Cl)=CN=C(NC2=CC=C(N3CCNCC3)C=C2)N=1

CTX0294885 Usage And Synthesis

Uses

CTX-0294885 is a broad spectrum kinase inhibitor that can capture 235 kinases from MDA-MB-231 cells, and can capture all members of the AKT family. CTX-0294885 is a powerful reagent for analysis of kinome signaling networks that can be used for the research of diseases like inflammation, diabetes, and cancer[1].

Biological Activity

ctx-0294885 is a novel bisanilino pyrimidine. it has inhibitory activity towards a wild range of kinases in vitro. ctx-0294885 is capable of capturing more than half of the expressed kinome in mda-mb-231 cells. large-scale ctx-0294885-based affinity purification with lc−ms/ms identifies 235 protein kinases. ctx-0294885 binds additional kinases that were not identified from previous studies using other kinase capture reagents. it is further developed into a sepharose-supported kinase capture reagent. ctx-0294885 is a new tool for analysis of kinome signaling networks. [1]

Synthesis

The reaction was carried out with 2-((2,5-dichloropyrimidin-4-yl)amino)-N-methylbenzamide (149 mg, 0.503 mmol) and 4-(piperazin-1-yl)aniline hydrochloride (134 mg, 0.627 mmol) as raw materials and stirred for 16 hr at 95 °C in the presence of 2,2,2-trifluoroethanol (5 mL) and concentrated aqueous hydrochloric acid solution (2 drops). Upon completion of the reaction, the mixture was cooled to room temperature, diluted with 5% aqueous sodium hydroxide solution (100 mL) and subsequently extracted with ethyl acetate (3 x 100 mL). The organic phases were combined, washed with saturated saline, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. Purification by reversed-phase column chromatography (12 g C18 column, 0-40% acetonitrile/methanol gradient elution) afforded the crude product was washed with dichloromethane (2 × 2 mL) and dried to afford the target compound 2-((5-chloro-2-((4-(piperazin-1-yl)phenyl)amino)pyrimidin-4-yl)amino)-N-methylbenzamide (33.4 mg, 15% yield) as an off-white solid.1H NMR (400 MHz, d6-DMSO) δ 9.19 (s, 1H), 8.78-8.71 (m, 2H), 8.15 (s, 1H), 7.74 (dd, J = 7.8, 1.3 Hz, 1H), 7.49-7.42 (m, 3H), 7.12 (t, J = 7.2 Hz, 1H), 6.86 ( d, J = 9.0 Hz, 2H), 3.00-2.95 (m, 4H), 2.86-2.79 (m, 7H).LCMS: retention time 4.28 min; m/z 438.1 [M + H]+.

References

1. zhang l, holmes ip, hochgräfe f et al. characterization of the novel broad-spectrumkinase inhibitor ctx-0294885 as an affinity reagent for mass spectrometry-basedkinome profiling. j proteome res. 2013 jul 5;12(7):3104-16.