| Identification | Back Directory | [Name]
N-[3-tert-Butyl-1-(quinolin-6-yl)-1H-pyrazol-5-yl]-N'-[2-fluoro-4-[(2-(methylcarbamoyl)pyridin-4-yl)oxy]phenyl]urea | [CAS]
1020172-07-9 | [Synonyms]
CS-1867
Rebastinib
DCC2036;DCC 2036
Rebastinib Tosylate
Rebastinib(DCC-2036)
DCC-2036 (Rebastinib)
DCC2036; DCC-2036; DCC 2036; REBASTINIB.
4-(4-(3-(3-(tert-Butyl)-1-(quinolin-6-yl)-1H-pyrazol-5-yl)ureido)-3-fluorophenoxy)-N-methylpic
N-[3-tert-Butyl-1-(quinolin-6-yl)-1H-pyrazol-5-yl]-N'-[2-fluoro-4-[(2-(MethylcarbaMoyl)pyridin-4-yl)
4-(4-(3-(3-(tert-Butyl)-1-(quinolin-6-yl)-1H-pyrazol-5-yl)ureido)-3-fluorophenoxy)-N-methylpicolinamide
4-[4-[(5-tert-butyl-2-quinolin-6-ylpyrazol-3-yl)carbamoylamino]-3-fluorophenoxy]-N-methylpyridine-2-carboxamide
1-(3-tert-butyl-1-(quinolin-6-yl)-1H-pyrazol-5-yl)-3-(2-fluoro-4-(2-(methylcarbamoyl)pyridin-4-yloxy)phenyl)urea
N-[3-tert-Butyl-1-(quinolin-6-yl)-1H-pyrazol-5-yl]-N'-[2-fluoro-4-[(2-(methylcarbamoyl)pyridin-4-yl)oxy]phenyl]urea
N-[3-tert-Butyl-1-(quinolin-6-yl)-1H-pyrazol-5-yl]-N'-[2-fluoro-4-[(2-(methylcarbamoyl)pyridin-4-yl)oxy]phenyl]urea USP/EP/BP
2-Pyridinecarboxamide, 4-[4-[[[[3-(1,1-dimethylethyl)-1-(6-quinolinyl)-1H-pyrazol-5-yl]amino]carbonyl]amino]-3-fluorophenoxy]-N-methyl-
N-[3-tert-Butyl-1-(quinolin-6-yl)-1H-pyrazol-5-yl]-N'-[2-fluoro-4-[(2-(methylcarbamoyl)pyridin-4-yl)oxy]phenyl]urea DCC-2036 (Rebastinib) | [Molecular Formula]
C30H28FN7O3 | [MDL Number]
MFCD19443646 | [MOL File]
1020172-07-9.mol | [Molecular Weight]
554 |
| Chemical Properties | Back Directory | [Melting point ]
>181°C (dec.) | [Boiling point ]
666.8±55.0 °C(Predicted) | [density ]
1.32 | [storage temp. ]
-20°C Freezer | [solubility ]
Methanol (Slightly) | [form ]
Solid | [pka]
12.25±0.70(Predicted) | [color ]
Off-White |
| Hazard Information | Back Directory | [Description]
Rebastinib is an orally bioavailable tyrosine kinase inhibitor that inhibits Abl1 (IC50 = 0.8 nM) as well as the gatekeeper mutant Abl1T315I (IC50 = 4 nM) and the activation loop mutant Abl1H396P.1 It also inhibits the Src family kinases Src, Lyn, Fgr, and Hck and the tyrosine kinases KDR, FLT3, and Tie2 at nanomolar concentrations. Rebastinib inhibits mutant Abl1T315I signaling and prolongs survival in a mouse Ba/F3 cell allograft model.1,2 Rebastinib also exhibits in vivo antineoplastic activity against cells with the T674I point mutation of FIP1-like-1-platelet-derived growth factor receptor α.3 | [Uses]
A conformational control inhibitor of Abl1 and Abl1-T315I with IC50s of 0.8 nM and 4 nM, respectively. | [Definition]
ChEBI: DCC-2036 is a member of the class of ureas that is urea in which one of the nitrogens bears a 3-tert-butyl-1-(quinolin-6-yl)-1H-pyrazol-5-yl substituent, while the other bears a 2-fluoro-4-{[2-(methylcarbamoyl)pyridin-4-yl]oxy}phenyl substituent. It has a role as a tyrosine kinase inhibitor. It is a member of quinolines, a pyridinecarboxamide, a member of pyrazoles, an organofluorine compound and a member of phenylureas. | [Synthesis]
Example 1: 4-(4-amino-3-fluorophenoxy)-N-methylpyridine-2-carboxamide (7.0 g, 15.8 mmol), compound (CAS:1011464-72-4, 4.14 g, 15.8 mmol) and N,N-diisopropylethylamine (DIEA, 4.5 g, 34.9 mmol) were dissolved in dimethyl sulfoxide (DMSO 70 ml). The reaction mixture was heated in an oil bath at 70°C for 8 hours. After completion of the reaction, the mixture was poured into water (500 ml), stirred overnight and the solid was collected by filtration. The crude product was purified by successive crystallization from toluene and acetone to afford 1-(3-tert-butyl-1-(quinolin-6-yl)-1H-pyrazol-5-yl)-3-(2-fluoro-4-(2-(methylcarbamoyl)pyridin-4-yloxy)phenyl)urea as a white crystalline solid (4.06 g, 46% yield). The product was characterized by 1H NMR (DMSO-d6) and mass spectrometry (ESI): 1H NMR δ 8.90 (m, 2H), 8.79 (m, 1H), 8.52 (m, 2H), 8.2 (m, 3H), 7.96 (dd, J = 9,2 Hz, 1H), 7.63 (dd, J = 8,4 Hz, 1H), 7.40 (br s, 1H) 7.30 (dd, J = 3,12 Hz, 1H), 7.17 (m, 1H), 7.05 (d, J = 9 Hz, 1H), 6.50 (s, 1H), 2.80 (d, J = 5Hz), 1.32 (s, 9H); MS (ESI) m/z: 554 (M + H+). | [in vivo]
A single dose of Rebastinib (DCC-2036; oral; 100 mg/kg) affords circulating plasma levels that exceeds 12 μM for up to 24 hours, and effectively inhibits BCR-ABL1 signaling for up to 8 hours in Ba/F3-BCR-ABL1T315I leukemia cells isolated from BM and spleen of tumor-bearing mice[1].
Treatment of mice bearing Ba/F3-BCR-ABL1T315I leukemia cells with Rebastinib at 100 mg/kg once daily by oral gavage significantly prolonged their survival, while STI571 at 100 mg/kg twice daily is ineffective[1].
In this aggressive allograft model, Rebastinib is as effective for treatment of BCR-ABLT315I leukemia as STI571 at 100 mg/kg twice daily in BCR-ABL1native leukemia, and reduces the leukemia cell burden in the spleens of treated mice[1].
| [References]
[1] chan w w, wise s c, kaufman m d, et al. conformational control inhibition of the bcr-abl1 tyrosine kinase, including the gatekeeper t315i mutant, by the switch-control inhibitor dcc-2036. cancer cell, 2011, 19(4): 556-568. |
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| Company Name: |
LETOPHARM LIMITED
|
| Telephone: |
+86-21-5821 5861 |
| Website: |
www.letopharm.com |
| Company Name: |
Tcichem, Inc.
|
| Telephone: |
13918644899 |
| Website: |
https://www.chemicalbook.com/ShowSupplierProductsList19113/0_EN.htm |
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