| Identification | More | [Name]
SGX-523 | [CAS]
1022150-57-7 | [Synonyms]
SGX-523
SGX 523(SGX-523)
6-[[6-(1-Methyl-1H-pyrazol-4-yl)-1,2,4-triazolo[4,3-b]pyridazin-3-yl]thio]quinoline
Quinoline,6-[[6-(1-Methyl-1H-pyrazol-4-yl)-1,2,4-triazolo[4,3-b]pyridazin-3-yl]thio]-
6-[[6-(1-Methyl-1H-pyrazol-4-yl)-1,2,4-triazolo[4,3-b]pyridazin-3-yl]thio]quinoline SGX 523 | [Molecular Formula]
C18H13N7S | [MDL Number]
MFCD16660190 | [MOL File]
1022150-57-7.mol | [Molecular Weight]
359.41 |
| Chemical Properties | Back Directory | [density ]
1.485 | [storage temp. ]
Store at -20°C | [solubility ]
≥17.95 mg/mL in DMSO | [form ]
solid | [pka]
3.94±0.10(Predicted) | [color ]
Light yellow to yellow | [InChI]
InChI=1S/C18H13N7S/c1-24-11-13(10-20-24)16-6-7-17-21-22-18(25(17)23-16)26-14-4-5-15-12(9-14)3-2-8-19-15/h2-11H,1H3 | [InChIKey]
BCZUAADEACICHN-UHFFFAOYSA-N | [SMILES]
N1C2C(=CC(SC3N4C(=NN=3)C=CC(C3=CN(C)N=C3)=N4)=CC=2)C=CC=1 |
| Hazard Information | Back Directory | [Uses]
SGX523 is a novel, ATP-competitive kinase inhibitor. | [Definition]
ChEBI: A member of the class of triazolopyridazines that is 6-(1-methylpyrazol-4-yl)[1,2,4]triazolo[4,3-b]pyridazine-3-thiol in which the thiol hydrogen is replaced by a quinolin-6-yl group. | [Biological Activity]
sgx-523 is a novel, potent, atp-competitive, and highly-selective hepatocyte growth factor receptor (met) inhibitor with ic50 value of 4 nm [1].sgx523 inhibits met autophosphorylation in gastric cancer cell line gtl16 and human lung carcinoma cell line a549, with ic50 of 40 nm and 12 nm, respectively [1]. additionally, tumor regression was observed in gastic cancer cell line gtl16 and human gbm cell line u87mg derived mouse xenograft models that are treated with sgx-523 by oral gavage [1].sgx523 has been shown to inhibit the phosphorylateion of mek, mapk, akt in brain cancer cell lines including u87, u373, daoy, as well as glioma stem cells 1228. the inhibition of mek in brain cancer cells and stem cells led to cell proliferation, g1/s cell cycle progression, cell migration, and cell invasion [2]. | [Synthesis]
Method b: 6-bromoquinoline (550 mg, 2.64 mmol) and diisopropylethylamine (1.13 mL, 6.46 mmol) were dissolved in N,N-dimethylacetamide (DMA, 4 mL) under nitrogen protection and degassed by nitrogen bubbling for 20 min. Subsequently, tris(dibenzylideneacetone)dipalladium (105 mg, 0.108 mmol, Strem catalyst), Xantphos (125 mg, 0.216 mmol), and 6-(1-methyl-1H-pyrazol-4-yl)-[1,2,4]triazolo[4,3-b]pyridazine-3-thiol (500 mg, 2.155 mmol ). The reaction mixture was stirred at 100 °C for 22 h until the solid was completely dissolved. After completion of the reaction, the mixture was cooled to room temperature and filtered through a short column of silica gel, using N,N-dimethylformamide (DMF) as eluent. The filtrate was poured directly into an ice/water mixture and allowed to stand for 15 minutes to precipitate the product. The precipitate was collected by filtration and washed with water. The resulting solid was ground with ether, filtered and dried under vacuum to give 770 mg of yellow crude product. The crude product was stirred in refluxing isopropanol for 1 h. The product was hot filtered, washed with isopropanol, and dried in a vacuum oven at 70 °C for 3 days to give a final 500 mg of 6-((6-(1-methyl-1H-pyrazol-4-yl)-[1,2,4]triazolo[4,3-b]pyridazin-3-yl)sulfanyl)quinoline as a yellow solid with 8% impurities (64% yield). | [in vivo]
SGX523 exhibits antitumor activity in vivo. SGX523 inhibits MET-dependent tumor growth[2]. | Animal Model: | Female Harlan nude mice (athymic nu/nu) were s.c. implanted with U87 cells[2] | | Dosage: | 10 or 30 mg/kg | | Administration: | Oral gavage; twice daily starting at day 5 for 22 days | | Result: | Potently inhibited U87MG tumor growth at a dose of 10 mg/kg administered twice daily.
Led to clear regression of U87MG tumors at 30 mg/kg dosed twice daily.
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| [storage]
Store at +4°C | [References]
[1] buchanan sg1, hendle j, lee ps, smith cr, bounaud py, jessen ka, tang cm, huser nh, felce jd, froning kj, peterman mc, aubol be, gessert sf,sauder jm, schwinn kd, russell m, rooney ia, adams j, leon bc, do th, blaney jm, sprengeler pa, thompson da, smyth l, pelletier la, atwell s, holme k,wasserman sr, emtage s, burley sk, reich sh. sgx523 is an exquisitely selective, atp-competitive inhibitor of the met receptor tyrosine kinase with antitumor activity in vivo. mol cancer ther. 2009 dec;8(12):3181-90.
[2] guessous f1, zhang y, dipierro c, marcinkiewicz l, sarkaria j, schiff d, buchanan s, abounader r.an orally bioavailable c-met kinase inhibitor potently inhibits brain tumor malignancy and growth. anticancer agents med chem. 2010 jan;10(1):28-35. |
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