GSK-2256098 Chemical Properties

Density 

1.32±0.1 g/cm3(Predicted)

storage temp. 

Store at -20°C

solubility 

DMSO:47.33(Max Conc. mg/mL);114.08(Max Conc. mM)
DMF:30.0(Max Conc. mg/mL);72.31(Max Conc. mM)
Ethanol:56.0(Max Conc. mg/mL);134.98(Max Conc. mM)
Ethanol:PBS (pH 7.2) (1:4):0.2(Max Conc. mg/mL);0.48(Max Conc. mM)

form 

A crystalline solid

pka

5.24±0.10(Predicted)

color 

White to khaki

InChI

InChI=1S/C20H23ClN6O2/c1-12(2)27-19(9-13(3)25-27)24-18-10-17(15(21)11-22-18)23-16-8-6-5-7-14(16)20(28)26-29-4/h5-12H,1-4H3,(H,26,28)(H2,22,23,24)

InChIKey

BVAHPPKGOOJSPU-UHFFFAOYSA-N

SMILES

C(NOC)(=O)C1=CC=CC=C1NC1C(Cl)=CN=C(NC2N(C(C)C)N=C(C)C=2)C=1

GSK-2256098 Usage And Synthesis

Description

GSK2256098 is an inhibitor of focal adhesion kinase (FAK). It is selective for FAK, inhibiting only FAK greater than 50% in a panel of 261 kinases. GSK2256098 inhibits FAK autophosphorylation at tyrosine 397 (Y397) in OVCAR8 ovarian, U87MG glioblastoma, and A549 lung cancer cell lines (IC₅₀s = 15, 8.5, and 12 nM, respectively). It induces apoptosis and increases PARP levels, decreases viability (IC₅₀ = 25 μM), and inhibits colony formation in L3.6P1 cells. GSK2256098 (75 mg/kg per day) also leads to lower tumor weight and fewer metastases in the Ishikawa orthotopic mouse model of uterine cancer.

Uses

GSK 2256098 is FAK inhibitor. It can be used in biological study of molecular pathways: endothelial cell FAK-?A target for cancer treatment.

Synthesis

Example 4: 1a Synthesis of 2-((5-chloro-2-((1-isopropyl-3-methyl-1H-pyrazol-5-yl)amino)pyridin-4-yl)amino)-N-methoxybenzamide 2-[(2,5-dichloro-4-pyridinyl)amino]-N-methoxybenzamide (70 mg, 0.224 mmol), 1-isopropyl-3-methyl-5-aminopyrazole (70 mg, 0.503 mmol) and cesium carbonate (230 mg, 0.706 mmol) were added sequentially to the microwave reaction tube. The reaction mixture was degassed with nitrogen for 10 min. BINAP (50 mg, 0.080 mmol) and palladium(II) acetate (10 mg, 0.045 mmol) were then added. The reaction mixture was placed in a microwave reactor and heated at 160 °C for 40 min. Upon completion of the reaction, the crude product was purified by reversed-phase high performance liquid chromatography (Gilson) using acetonitrile/water containing 0.1% formic acid as eluent to afford the target compound 2-((5-chloro-2-((1-isopropyl-3-methyl-1H-pyrazol-5-yl)amino)pyridin-4-yl)amino)-N-methoxybenzamide (15 mg, 15% yield). Mass spectrum (MS): M(C20H23ClN6O2)=414.89, (M+H)+=415,416; 1H NMR (400 MHz, chloroform-d) δ ppm 9.42(br.s, 1H), 8.71(br.s, 1H), 8.02(s, 1H), 7.54(br.s., 1H), 7.06(t, J= 7.5 Hz, 1H), 6.48(s, 1H), 6.32(br.s., 1H), 5.86(s, 1H), 4.47(dt, J=13.4,6.7 Hz, 1H), 3.92(s, 3H), 2.26(s, 3H), 1.41-1.43(d, J=6.6Hz, 6H).

in vivo

storage

Store at -20°C

References

[1] Patent: US2010/113475, 2010, A1. Location in patent: Page/Page column 23-24
[2] Patent: WO2013/3575, 2013, A1. Location in patent: Page/Page column 53

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