722544-51-6 Usage
Description
1H-Pyrazole-3-acetamide, 5-[[7-[3-[ethyl(2-hydroxyethyl)amino]propoxy]-4-quinazolinyl]amino]-N-(3-fluorophenyl)-, also known as AZD1152-HQPA, is a potent and highly selective inhibitor of Aurora B kinase with a Ki value of 0.36 nM for Aurora B and 1,369 nM for Aurora A. It has been shown to inhibit the growth of tumors in multiple cancer models and has been proposed to have novel mechanisms of cytotoxicity, including excessive ROS generation and upregulated tumor suppressor miRNAs.
Uses
Used in Cancer Research:
1H-Pyrazole-3-acetamide, 5-[[7-[3-[ethyl(2-hydroxyethyl)amino]propoxy]-4-quinazolinyl]amino]-N-(3-fluorophenyl)is used as a highly selective inhibitor of Aurora B kinase for the inhibition of tumor growth in various cancer models. It has been shown to be effective in inhibiting the proliferation of osteosarcoma cell line U2-OS and as an apoptosis-inducing agent in acute myeloid leukemia cell lines and primary cultures.
Used in Cell Biology Research:
1H-Pyrazole-3-acetamide, 5-[[7-[3-[ethyl(2-hydroxyethyl)amino]propoxy]-4-quinazolinyl]amino]-N-(3-fluorophenyl)is used as a component to study the regulation of abscission timing in human cells, identifying replication timing regulatory factor 1 (RIF1) and protein phosphatase 1 (PP1) as critical factors.
Used in Drug Discovery:
1H-Pyrazole-3-acetamide, 5-[[7-[3-[ethyl(2-hydroxyethyl)amino]propoxy]-4-quinazolinyl]amino]-N-(3-fluorophenyl)is used as a component to investigate the relevance of Aurora B kinase (AURKB) as a cancer therapeutic target, aiding in the development of potential drugs for cancer treatment.
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.
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
Check Digit Verification of cas no
The CAS Registry Mumber 722544-51-6 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 7,2,2,5,4 and 4 respectively; the second part has 2 digits, 5 and 1 respectively.
Calculate Digit Verification of CAS Registry Number 722544-51:
(8*7)+(7*2)+(6*2)+(5*5)+(4*4)+(3*4)+(2*5)+(1*1)=146
146 % 10 = 6
So 722544-51-6 is a valid CAS Registry Number.
InChI:InChI=1/C26H30FN7O3/c1-2-34(10-11-35)9-4-12-37-21-7-8-22-23(16-21)28-17-29-26(22)31-24-14-20(32-33-24)15-25(36)30-19-6-3-5-18(27)13-19/h3,5-8,13-14,16-17,35H,2,4,9-12,15H2,1H3,(H,30,36)(H2,28,29,31,32,33)
722544-51-6Relevant articles and documents
Preparing method of Barasertib
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, (2018/03/26)
The invention discloses a preparing method of Barasertib. The chemical name of Barasertib is 2-5{-[(7-{3-[ethyl(2-hydroxyethyl)amino]propoxy}quinazoline-4-group)amino]-1H-pyrazole-3-group}-N-(3-fluorophenyl)acetamide, and the chemical formula of Barasertib is C26H30FN7O3. According to the preparing method of Barasertib, the preparing process is simple, raw materials are easy to obtain, the preparing method is economical and environmentally friendly, industrialization is easy to achieve, the economic technology development of Barasertib raw material medicine can be promoted, the production costis lowered, and the preparing method is suitable for large-scale production.
COMBINATION THERAPY FOR THE TREATMENT OF CANCER
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, (2008/06/13)
A combination comprising an aurora kinase inhibitor and an efflux transporter inhibitor wherein the aurora kinase inhibitor is a compound of formula (I) or pharmaceutically acceptable salt thereof for use in the treatment of hyperproliferative diseases such as cancer.
PROCESS AND INTERMEDIATE
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Page/Page column 9; 11, (2008/06/13)
The invention relates to a new process useful in the preparation of pharmaceutical compounds such as 2-{ethyl[3-({4-[(5-{2-[(3-fluorophenyl)amino]-2-oxoethyl}-1H-pyrazol-3-yl)amino]quinazolin-7-yl}oxy)propyl]amino}ethyl dihydrogen phosphate (AZD1152) and intermediates used therein.
