288383-20-0

Basic information

• Product Name: Cediranib
• Synonyms: Cediranib;4-(4-Fluoro-2-methylindol-5-yloxy)-6-methoxy-7-[3-(pyrrolidin-1-yl)propoxy]quinazoline;Cadiranib (AZD2171);Cediranib(AZD2171);AZD2171;Recentin;Cadiranib;Cediranib R
• CAS NO: 288383-20-0
• Molecular Formula: C25H27FN4O3
• Molecular Weight: 450.51
• EINECS: 1308068-626-2
• Product Categories: APIs;Antineoplastic;Inhibitors
• Mol File: 288383-20-0.mol
• Article Data: 9

Chemical Properties

• Boiling Point: 626.557 °C at 760 mmHg
• Flash Point: 332.73 °C
• Appearance: /
• Density: 1.285
• Vapor Pressure: 0mmHg at 25°C
• Refractive Index: 1.642
• Storage Temp.: Sealed in dry,Store in freezer, under -20°C
• Solubility: Acetone (Slightly), DMSO (Slightly), Methanol (Slightly)
• PKA: 16.14±0.30(Predicted)
• CAS DataBase Reference: Cediranib(CAS DataBase Reference)
• NIST Chemistry Reference: Cediranib(288383-20-0)
• EPA Substance Registry System: Cediranib(288383-20-0)

Safety Data

• Hazardous Substances Data: 288383-20-0(Hazardous Substances Data)

Usage

Anticancer drugs

Cediranib is an oral anticancer drug , it is successfully developed by the US AstraZeneca company , its trade name is recentin, this product is an efficient VEGFR tyrosine kinase inhibitor, it is capable of inhibiting all known VEGFR tyrosine kinases ( including VEGFR-1, VEGFR-2, VEGFR-3, and PDGFR). Cediranib can inhibit VEGF-induced angiogenesis, neovascularization survival and human tumor xenograft cell growth.Clinical trail phase I for non-small cell lung cancer (abbreviated NSCLC) patients shows that cediranib in combination with PC programs has a significant antitumor effect . Clinical trail phaseⅡ/Ⅲ BR24 focuses on using cediranib 30mg as a first-line treatment of NSCLC ,which demonstrates that it has anti-tumor effect, but it has a higher incidence of adverse events, including diarrhea, dehydration, hand-foot syndrome, hypertension and neutropenia disease. Therefore, there is the decision to stop clinical trials. Repeated assessments about toxicity and dose of the combination of drugs suggest that part of the adverse effects are dose-related , dose reduction may be tried to improve drug tolerance. In view of this conclusion, in 2009, the National Cancer Institute of Canada Clinical Trials Group (NCIC CTG) launched a cediranib clinical trail phase Ⅲ (BR29) for progressive NSCLC patients , the dose was adjusted to 20mg. The results have not been reported. In 2009 ,European Society for Medical Oncology (ESMO) Annual report which is about cediranib treatment of metastatic renal cell carcinoma (referred mRCC) clinical trail phase II shows that cediranib treatment group tumor volume reducing rate is higher than the placebo group. Zurita tested Cediranib pretreatment serum cytokines and angiogenic factors ,and found that patients having low IL-10, VEGF, PIGF, SCF and MIG concentration during baseline time , have the more obvious tumor volume reduction after treatment. The above information is edited by the lookchem of Tian Ye.

Description

Receptors for VEGF have central roles in vasculogenesis and angiogenesis and thus serve as targets for cancer therapy. Cediranib is a potent inhibitor of VEGF receptor tyrosine kinases, including VEGFR1, 2, and 3 (IC50s = 5, 1, and 3 nM, respectively). It also potently inhibits a variety of other receptor and non-receptor tyrosine kinases, including several in the platelet-derived growth factor, fibroblast growth factor, and endothelial growth factor receptor families. Cediranib blocks tubule formation by human umbilical vein endothelial cells in vitro and prevents angiogenesis as well as xenograft tumor growth in vivo. Because of these effects, cediranib has potential use in a range of cancers.

Uses

Different sources of media describe the Uses of 288383-20-0 differently. You can refer to the following data:
1. Cediranib (AZD2171) inhibited VEGF-stimulated proliferation and KDR phosphorylation with IC50 of 0.4 and 0.5 nM, respectively.
2. Cediranib is a drug for blocking angiogenesis, study on cervical cancer molecular targeted drug and clinical application progress, value of correlative biomakers in the understanding of tumor biology.

references

[1] wedge sr, kendrew j, hennequin lf, valentine pj, barry st, brave sr, smith nr, james nh, dukes m, curwen jo, chester r, jackson ja, boffey sj, kilburn ll, barnett s, richmond gh, wadsworth pf, walker m, bigley al, taylor st, cooper l, beck s, jürgensmeier jm, ogilvie dj. azd2171: a highly potent, orally bioavailable, vascular endothelial growth factor receptor-2 tyrosine kinase inhibitor for the treatment of cancer. cancer res. 2005 may 15;65(10):4389-400.

InChI:InChI=1/C25H27FN4O3/c1-16-12-17-19(29-16)6-7-21(24(17)26)33-25-18-13-22(31-2)23(14-20(18)27-15-28-25)32-11-5-10-30-8-3-4-9-30/h6-7,12-15,29H,3-5,8-11H2,1-2H3

Upstream product

• 39743-20-9 1-(3-chloropropyl)pyrrolidine 
• 403-19-0 2-fluoro-4-nitrophenol 
• 199327-75-8 4-hydroxy-6-methoxy-7-(3-(pyrrolidin-1-yl)propoxy)quinazoline 
• 74-99-7 prop-1-yne 
• 385785-04-6 N’-(2-cyano-5-(3-chloropropoxy)-4-methoxyphenyl)-N,N-dimethylformamidine 
• 162012-72-8 7-hydroxy-6-methoxy-3,4-dihydroquinazolin-4-one 
• 288385-88-6 4-fluoro-2-methyl-1H-indol-5-ol 
• 199327-69-0 4-chloro-6-methoxy-7-(3-(pyrrolidin-1-yl)propoxy)quinazoline 
• 574745-75-8 7-(benzyloxy)-4-[(4-fluoro-2-methyl-1H-indol-5-yl)-oxy]-6-methoxyquinazoline 
• 574745-76-9 7-hydroxy-4-(4-fluoro-2-methyl-1H-indol-5-yloxy)-6-methoxyquinazoline 
• 1022112-44-2 4-azoniaspiro[3,4]octane bromide 
• 1022112-38-4 4-azaspiro[3.4]octan-4-ium chloride 

Downstream Products

• 857036-77-2 cediranib maleate 

Relevant articles and documents

Understanding the Alkylation of a Phenol by 1-(3-Chloropropyl)pyrrolidine: Evidence for the Intermediacy of an Azetidinium Ion

The final synthetic step in the synthesis of cediranib, AZD2171, 1, is the alkylation of a phenol with an alkyl halide to generate an ether. Our need to understand and control the formation of synthetic impurities generated in this step of the synthesis led us to investigate the kinetics and mechanism of the alkylation of indolphenol, 2, 4-[(4-fluoro-2-methyl-1H-indol-5-yl)oxy]-6-methoxyquinazolin-7-ol, by chloropyrrolidine, 3, 1-(3-chloropropyl)pyrrolidine. Studies in 1-methyl-2-pyrrolidinone (NMP) established that the active alkylating agent is the azetidinium ion, 4, 4-azoniaspiro[3.4]octane, formed via a slow intramolecular cyclization reaction of chloropyrrolidine, 3. The azetidinium ion was isolated as its tetraphenylborate salt from water by heating 3 in the presence of aqueous potassium tetraphenyl borate, and its competence as an intermediate was demonstrated by its fast reaction with 2 to yield cediranib, 1.

Preparation methods for drug cediranib treating non-small cell lung cancer and kidney cancer and intermediate thereof

The invention discloses preparation methods for a drug cediranib treating non-small cell lung cancer and kidney cancer and an intermediate thereof. The chemical name of the drug cediranib treating non-small cell lung cancer and kidney cancer is 4-(4-fluoro-2-methylindol-5-yloxy)-6-methoxy-7-[3-(pyrrolidin-1-yl)propoxy]quinazoline, and the structural formula thereof is as shown in the description.The preparation methods are simple, the cediranib intermediate and 5-hydroxy-4-fluoro-2-methylindole are synthesized to obtain cediranib through a condensation reaction, so that the atom is more economical, the reaction is more selective, and the operation is more controllable, the preparation method for the cediranib is more controllable, the product quality is improved, and the economic technology of active ingredients is advanced.

SOLID STATE FORMS OF CEDIRANIB MALEATE

The present disclosure relates to solid state forms of Cediranib maleate, processes for preparation thereof and pharmaceutical compositions thereof.