848942-61-0 Usage
Description
AZD8931 is a member of the class of quinazolines, specifically 4-amino-7-methoxyquinazoline, with a 3-chloro-2-fluorophenyl group substitution on the amino group and a 1-[2-(methylamino)-2-oxoethl]piperidin-4-yloxy group substitution at position 6 of the quinoline ring. It is a dual tyrosine kinase inhibitor (TKI) of epithelial growth factor receptors (EGFR) HER2 and HER3.
Uses
Used in Pharmaceutical Industry:
AZD8931 is used as a dual tyrosine kinase inhibitor for targeting the HER2 and HER3 receptors, which play a crucial role in the growth and proliferation of cancer cells. Its application in this industry is aimed at treating various types of cancer by inhibiting the activity of these receptors and thus, limiting tumor growth and progression.
Used in Cancer Treatment:
AZD8931 is used as an anticancer agent for the treatment of various malignancies, particularly those that overexpress HER2 and HER3 receptors. By inhibiting the activity of these receptors, AZD8931 can help control tumor growth and potentially improve patient outcomes in combination with other cancer therapies.
Used in Research Applications:
AZD8931 is also used as a research tool in the study of the role of HER2 and HER3 receptors in cancer development and progression. Its application in research settings helps scientists better understand the mechanisms of action and potential therapeutic targets for the development of new cancer treatments.
Enzyme inhibitor
This signal transduction kinase inhibitor (FW = 473.94 g/mol; CAS 848942-61-0), also named 2-(4-[4-(3-chloro-2-fluorophenylamino)-7- methoxyquinazolin-6-yloxy]piperidin-1-yl)-N-methylacetamide, reversibly inhibits EGFR (IC50 = 4 nM), erbB2 (IC50 = 3 nM), and erbB3 (IC50 = 4 nM) phosphorylation in cells. In proliferation assays, AZD8931 is significantly more potent than gefitinib or lapatinib in specific squamous cell carcinoma of the head and neck and non-small cell lung carcinoma cell lines. In vivo, AZD8931 inhibits xenograft growth in a range of models, while significantly affecting EGFR, erbB2, and erbB3 phosphorylation and downstream signaling pathways, apoptosis, and proliferation. In EGF and HRG ligand-driven cell systems, AZD8931 is more potent than gefitinib or lapatinib. Metabolic disposition of AZD8931.
Check Digit Verification of cas no
The CAS Registry Mumber 848942-61-0 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 8,4,8,9,4 and 2 respectively; the second part has 2 digits, 6 and 1 respectively.
Calculate Digit Verification of CAS Registry Number 848942-61:
(8*8)+(7*4)+(6*8)+(5*9)+(4*4)+(3*2)+(2*6)+(1*1)=220
220 % 10 = 0
So 848942-61-0 is a valid CAS Registry Number.
InChI:InChI=1S/C23H25ClFN5O3/c1-26-21(31)12-30-8-6-14(7-9-30)33-20-10-15-18(11-19(20)32-2)27-13-28-23(15)29-17-5-3-4-16(24)22(17)25/h3-5,10-11,13-14H,6-9,12H2,1-2H3,(H,26,31)(H,27,28,29)
848942-61-0Relevant articles and documents
The Development of a Dimroth Rearrangement Route to AZD8931
Goundry, William R. F.,Boardman, Kay,Cunningham, Oliver,Evans, Matthew,Jones, Martin F.,Millard, Kirsty,Rozada-Sanchez, Raquel,Sawyer, Yvonne,Siedlecki, Paul,Whitlock, Brian
, p. 336 - 345 (2017/03/24)
Recently, the aminoquinazoline motif has been highly prevalent in anticancer pharmaceutical compounds. Synthetic methods are required to make this structure on a multikilo scale and in high purity. The initial route to aminoquinazoline AZD8931 suffered from the formation of late-stage impurities. To avoid these impurities, a new high-yielding Dimroth rearrangement approach to the aminoquinazoline core of AZD8931 was developed. Assessment of route options on a gram scale demonstrated that the Dimroth rearrangement is a viable approach. The processes were then evolved for large-scale production with learning from a kilo campaign and two plant-scale manufactures. Identification of key process impurities offers an insight into the mechanisms of the Dimroth rearrangement as well as the hydrogenation of a key intermediate. The final processes were operated on a 30 kg scale delivering the target AZD8931 in 41% overall yield.
Discovery of AZD8931, an equipotent, reversible inhibitor of signaling by EGFR, HER2, and HER3 receptors
Barlaam, Bernard,Anderton, Judith,Ballard, Peter,Bradbury, Robert H.,Hennequin, Laurent F. A.,Hickinson, D. Mark,Kettle, Jason G.,Kirk, George,Klinowska, Teresa,Lambert-Van Der Brempt, Christine,Trigwell, Cath,Vincent, John,Ogilvie, Donald
, p. 742 - 746 (2013/09/02)
Deregulation of HER family signaling promotes proliferation and tumor cell survival and has been described in many human cancers. Simultaneous, equipotent inhibition of EGFR-, HER2-, and HER3-mediated signaling may be of clinical utility in cancer settings where the selective EGFR or HER2 therapeutic agents are ineffective or only modestly active. We describe the discovery of AZD8931 (2), an equipotent, reversible inhibitor of EGFR-, HER2-, and HER3-mediated signaling and the structure-activity relationships within this series. Docking studies based on a model of the HER2 kinase domain helped rationalize the increased HER2 activity seen with the methyl acetamide side chain present in AZD8931. AZD8931 exhibited good pharmacokinetics in preclinical species and showed superior activity in the LoVo tumor growth efficacy model compared to close analogues. AZD8931 is currently being evaluated in human clinical trials for the treatment of cancer.
NOVEL SALT-554
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Page/Page column 14-15, (2009/12/05)
4-(3-chloro-2-fluoroanilino)-7-methoxy-6-{[1-(N-methylcarbamoylmethyl)piperidin-4-yl]oxy}quinazoline difumarate, pharmaceutical compositions containing the difumarate, the use of the difumarate in the treatment of hyperproliferative disorders such as canc
