| Identification | Back Directory | [Name]
Barasertib (AZD1152-HQPA) | [CAS]
722544-51-6 | [Synonyms]
INH 34
Barasertib
AZD1152 HPQA
AZD-1152HQPA
AZD1152-HQPA
AZD1152-HQPA(Barasertib)
Barasertib (AZD1152-HQPA)
2-[5-(7-{3-[Ethyl-(2-hydroxy-ethyl)-aMino]-propoxy}-quinazolin-4-ylaMino)-2H-pyr
3-[[7-[3-[Ethyl(2-hydroxyethyl)amino]propoxy]-4-quinazolinyl]amino]-N-(3-fluorophenyl)-1H-pyrazole-5-acetamide
5-[[7-[3-[Ethyl(2-hydroxyethyl)amino]propoxy]-4-quinazolinyl]amino]-N-(3-fluorophenyl)-1H-pyrazole-3-acetamide
1H-Pyrazole-3-acetamide, 5-[[7-[3-[ethyl(2-hydroxyethyl)amino]propoxy]-4-quinazolinyl]amino]-N-(3-fluorophenyl)-
2-(3-(7-(3-(Ethyl(2-hydroxyethyl)amino)propoxy)quinazolin-4-ylamino)-1H-pyrazol-5-yl)-N-(3-fluorophenyl)acetamide
2-(5-(7-(3-(ethyl(2-hydroxyethyl)amino)propoxy)quinazolin-4-ylamino)-1H-pyrazol-3-yl)-N-(3-fluorophenyl)acetamide
2-[5-(7-{3-[ETHYL-(2-HYDROXY-ETHYL)-AMINO]-PROPOXY}-QUINAZOLIN-4-YLAMINO)-2H-PYRAZOL-3-YL]-N-(3-FLUORO-PHENYL)-ACETAMIDE
AZD1152-HQPA
5-[[7-[3-[Ethyl(2-hydroxyethyl)amino]propoxy]-4-quinazolinyl]amino]-N-(3-fluorophenyl)-1H-pyrazole-3-acetamide
5-[[7-[3-[Ethyl(2-hydroxyethyl)amino]propoxy]-4-quinazolinyl]amino]-N-(3-fluorophenyl)-1H-pyrazole-3-acetamide AZD1152-HQPA | [Molecular Formula]
C26H30FN7O3 | [MDL Number]
MFCD10687152 | [MOL File]
722544-51-6.mol | [Molecular Weight]
507.56 |
| Chemical Properties | Back Directory | [Boiling point ]
796.7±60.0 °C(Predicted) | [density ]
1.359±0.06 g/cm3(Predicted) | [storage temp. ]
2-8°C | [solubility ]
DMSO: >15mg/mL | [form ]
powder | [pka]
13.07±0.10(Predicted) | [color ]
white to beige | [Stability:]
Stable for 1 year from date of purchase as supplied. Solutions in DMSO may be stored at -20° for up to 1 month. | [InChIKey]
QYZOGCMHVIGURT-UHFFFAOYSA-N | [SMILES]
N1C(NC2=C3C(=NC=N2)C=C(OCCCN(CC)CCO)C=C3)=CC(CC(NC2=CC=CC(F)=C2)=O)=N1 | [CAS DataBase Reference]
722544-51-6 |
| Hazard Information | Back Directory | [Usage]
AZD1152-HQPA is a a highly selective inhibitor of aurora-B kinase. AZD1152-HQPA has been shown to inhibit osteosarcoma cell line U2-OS cells proliferation. AZD1152-HQPA was also shown to be an effective apoptosis-inducing agent in acute myeloid leukemia cell lines and primary acute myeloid leukemia cultures. | [Description]
AZD1152-HQPA (722544-51-6) is a potent and highly selective inhibitor of Aurora B.1?Aurora B Ki?= 0.36 nM; Aurora A Ki?= 1,369 nM.2?It inhibits the growth of tumors in multiple cancer models.3-6?Excessive ROS generation7?and upregulated tumor suppressor miRNAs8?have been proposed as a novel mechanisms of cytotoxicity of AZD1152-HQPA. | [Uses]
AZD1152-HQPA has been used:
- for the dose dependent inhibition of aurora kinase B (AURKB)
- as a component to identify that, replication timing regulatory factor 1 (RIF1) and protein phosphatase 1 (PP1) are critical for the regulation of abscission timing in human cells
- as a component to study the relevance of AURKB as a cancer therapeutic target
| [Uses]
AZD1152-HQPA is a a highly selective inhibitor of aurora-B kinase. AZD1152-HQPA has been shown to inhibit osteosarcoma cell line U2-OS cells proliferation. AZD1152-HQPA was also shown to be an effective apoptosis-inducing agent in acute myeloid leukemia cell lines and primary acute myeloid leukemia cultures. | [Definition]
ChEBI:AZD-1152 is a member of the of quinazolines that is 4-aminoquinazolin-7-ol in which the amino group at position 4 has been substituted by a 5-[2-(3-fluoroanilino)-2-oxoethyl]-1H-pyrazol-3-yl group, while the hydroxy group at position 7 has been converted into the corresponding 3-[ethyl(2-hydroxyethyl)aminopropyl ether. It has a role as an antineoplastic agent and an Aurora kinase inhibitor. It is a member of quinazolines, a secondary carboxamide, a tertiary amino compound, a secondary amino compound, a member of pyrazoles, a primary alcohol, a member of monofluorobenzenes and an anilide. | [Biochem/physiol Actions]
AZD1152-HQPA is the active metabolite of AZD-1152, a potent selective Aurora Kinase B inhibitor. AZD1152 is 50-fold selective for Aurora kinase B over Aurora kinase C and over 1000-fold selective for Aurora kinase B over Aurora Kinase A. (IC50s: aurora-A, 1,369 nmol/L; aurora-B, 0.36 nmol/L; aurora-C, 17.0 nmol/L). It is converted in plasma to the active form AZD1152-HQPA, which has been shown to have antineoplastic activity in a variety of animal models and human cancer cell lines. | [Synthesis]
The general procedure for the synthesis of 2-(5-((7-(3-(3-(ethyl(2-hydroxyethyl)amino)propoxy)quinazolin-4-yl)amino)-1H-pyrazol-3-yl)-N-(3-fluorophenyl)acetamide, using the compound (CAS:722544-46-9) and N-ethyl ethanolamine, was carried out as follows: firstly, in an inert atmosphere (e.g., protected by nitrogen), 2-(3-(3-(3-(3-chloropropoxy)quinazolin-4-yl)amino}-1H-pyrazole-5-yl)-N-(3-fluorophenyl)acetamide was synthesized as follows. {[7-(3-chloropropoxy)quinazolin-4-yl]amino}-1H-pyrazol-5-yl)-N-(3-fluorophenyl)acetamide and N-ethyl ethanolamine were dissolved in N,N-dimethylacetamide under an inert atmosphere (e.g., nitrogen protection). Subsequently, the reaction mixture was heated to 90°C under stirring and maintained at this temperature for 12-16 hours (optimally 12 hours). Upon completion of the reaction, the mixture was cooled to about 85°C and water was slowly added to maintain the temperature between 80-85°C. The temperature of the mixture was adjusted to 80°C and a crystal seed with an expected yield of about 1% was added to induce crystallization. Over the next about 20 hours, the mixture was slowly cooled to 20°C to ensure that the product precipitated in the desired crystalline form and that the crystals were of suitable size for filtration. The product was collected by filtration, washed sequentially with a water/N,N-dimethylacetamide mixture and acetonitrile, and subjected to appropriate de-liquefaction to give the product in hydrated form. Subsequently, the filter cake was slurried with warm acetonitrile (about 40°C) for about 2 hours, filtered again, washed with acetonitrile, and finally dried under vacuum or nitrogen flow to give virtually anhydrous 2-{3-[(7-{3-[ethyl(2-hydroxyethyl)amino]propoxy}- quinazolin-4-yl)amino]-1H-pyrazol-5-yl}-N-(3-fluorophenyl)acetamide as an off-white solid in yields of 85-90%. The product was confirmed by 1H-NMR (DMSO-d6) and mass spectrometry (+ve ESI), the characteristic signals and molecular ion peaks were as follows: 1H-NMR (DMSO-d6): δ 10.55 (s, 1H), 9.45 (br s, 1H), 8.98 (s, 1H), 8.8 (d, 1H), 7.63 (m, 1H), 7.47 (pr d 1H), 7.37 (m, 2H), 7.32 (d, 1H), 6.9 (m, 1H), 6.77 (s, 1H), 4.32 (t, 2H), 3.83 (br s, 2H), 3.76 (t, 2H), 3.35 (m, 2H), 3.25 (m, 4H), 2.25 (m, 2H), 1.25 (t, 3H); MS (+ve ve ESI): m/z 508.4 (M + H)+. | [target]
Aurora B | [storage]
Store at -20°C | [References]
1) Mortlock?et al. (2007)?Discovery, Synthesis, and in Vivo Activity of a New Class of Pyrazoloquinazolines as Selective Inhibitors of Aurora B Kinase; J. Med. Chem.?50?2213
2) Wilkinson?et al.?(2007)?AZD1152, a Selective Inhibitor of Aurora B Kinase, Inhibits Human Tumor Xenograft Growth by Inducing Apoptosis; Clin. Cancer Res.?13?3682
3) Oke?et al.?(2009)?AZD1152 rapidly and negatively affects the growth and survival of human acute myeloid leukemia cells in vitro and in vivo; Cancer Res.?69?4150
4) Aihara?et al.?(2010)?The selective Aurora B kinase inhibitor AZD1152 as a novel treatment for hepatocellular carcinoma; J. Hepatol.?52?63
5) Mori?et al.?(2011)?Effects of AZD1152, a selective Aurora B kinase inhibitor of Burkitt’s and Hodgkin’s lymphomas; Biochem. Pharmacol.?82?1252
6) Helfrich?et al.?(2016)?Barasertib (AZD1152), a Small Molecule Aurora B Inhibitor, Inhibits the Growth of SCLC Cell Lines In Vitro and In Vivo; Mol. Cancer Ther.?15?2314
7) Zekri?et al.?(2017)?Reactive oxygen species generation and increase in mitochondrial copy number: new insight into the potential mechanism of cytotoxicity induced by aurora kinase inhibitor, AZD1152-HQPA; Anticancer Drugs?28?841
8) Zekri?et al.?(2018)?The Potential Contribution of microRNAs in Anti-cancer Effects of Aurora Kinase Inhibitor (AZD1152-HQPA); J. Mol. Neurosci.?65?444 |
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