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

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

Uses

Used in Oncology:
Cediranib is used as an anti-cancer agent for blocking angiogenesis, which is a critical process for tumor growth and progression. It has shown potential in the treatment of various cancers, including cervical cancer, by inhibiting VEGF-stimulated proliferation and KDR phosphorylation with IC50 values of 0.4 and 0.5 nM, respectively.
Used in Molecular Targeted Drug Research:
Cediranib is used as a molecular targeted drug in the study of cervical cancer, where it has shown promise in understanding tumor biology and the development of personalized treatment strategies.
Used in Clinical Applications:
Cediranib is used in clinical applications to evaluate its efficacy and safety in cancer treatment. The drug's ability to inhibit a variety of receptor and non-receptor tyrosine kinases makes it a valuable candidate for further research and development in oncology.
Used in Biomarker Research:
Cediranib is used in the study of correlative biomarkers to better understand tumor biology and predict treatment response. This research can help identify patients who are more likely to benefit from Cediranib treatment and improve the overall effectiveness of cancer therapy.

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.

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 
• 574745-76-9 7-hydroxy-4-(4-fluoro-2-methyl-1H-indol-5-yloxy)-6-methoxyquinazoline 
• 1022112-38-4 4-azaspiro[3.4]octan-4-ium chloride 
• 1022112-44-2 4-azoniaspiro[3,4]octane bromide 
• 574745-75-8 7-(benzyloxy)-4-[(4-fluoro-2-methyl-1H-indol-5-yl)-oxy]-6-methoxyquinazoline 
• 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 
• 162012-72-8 7-hydroxy-6-methoxy-3,4-dihydroquinazolin-4-one 
• 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 

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 method for anti-cancer drug of Cediranib

The invention discloses a preparation method for an anti-cancer drug of Cediranib. According to the preparation method, the chemical name of the anti-cancer drug of the Cediranib is 4-(4-fluoro-2-methylindole-5-yloxy)-6-methoxy-7-[3-(pyrrolidine-1-yl)propoxy] quinazoline, the chemical formula of the anti-cancer drug of the Cediranib is C25H27FN4O3, and the structural formula of the anti-cancer drug of the Cediranib is as shown in the specification. The preparation method has the advantages that the 4-(4-fluoro-2-methylindole-5-yloxy)-6-methoxy-7-[3-(pyrrolidine-1-yl)propoxy] quinazoline is generated through etherification reaction and reduction reaction, the Cediranib is finally generated through oxidation cyclization reaction, and therefore the phenomenon that chlorinating agents such asphosphorus trichloride, phosphorus pentachloride, thionyl chloride, phosgene and phosphorus oxychloride which are harmful to the environment are used due to the fact that the Cediranib is synthesizedthrough existing chlorination reaction can be avoided, the environment can be protected, the technological process is simple, the method is rapid and convenient, raw materials are easy to obtain, economical and environmentally friendly, the product yield and the product purity are high, the quality is controllable, and the method is suitable for industrial production.

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.

Preparation method of vascular endothelial growth factor (VEGF) receptor tyrosine kinase inhibitor Cediranib

The invention discloses a preparation method of a vascular endothelial growth factor (VEGF) receptor tyrosine kinase inhibitor Cediranib. The chemical name of the VEGF receptor tyrosine kinase inhibitor Cediranib is 4-(4-fluoro-2-methylindol-5-yloxy)-6-methoxy-7-[3-(pyrrolidin-1-yl)propoxy]quinazoline, the chemical formula is C25H27FN4O3, and the structural formula is shown in the description. A preparation technology which adopts readily-available raw materials and is economical and environmentally friendly is adopted, a process method suitable for industrial production is found, the preparation process is novel, and the reaction process is simplified, so that the reaction yield is increased; the preparation method has important significance to the improvement on the economical and socialbenefits of the Cediranib.

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.

west Neeb salt and its crystalline form, and its preparation method and pharmaceutical composition (by machine translation)

The invention relates to west Neeb salt and its crystalline form, compared with the prior art, and its west Neeb salt of the invention the crystalline form has more excellent in water solubility. The present invention also relates to the west states the Neeb salt and its crystal preparation method, the medicament composition and its use in treating and/or preventing the pathological angiogenic diseases use of the medicament. (by machine translation)

CHEMICAL PROCESS

The present invention relates to chemical processes for the manufacture of certain quinazoline derivatives, or pharmaceutically acceptable salts thereof. The invention also relates to processes for the manufacture of certain intermediates useful in the manufacture of the quinazoline derivatives and to processes for the manufacture of the quinazoline derivatives utilising said intermediates. In particular, the present invention relates to chemical processes and intermediates useful in the manufacture of the compound 4-(4-fluoro-2-methylindol-5-yloxy)-6-methoxy-7-(3-pyrrolidin-1-ylpropoxy)quinazoline.

QUINAZOLINE DERIVATIVES AS ANGIOGENESIS INHIBITORS

The invention relates to the use of compounds of the formula I: wherein ring C is an 8, 9, 10, 12 or 13-membered bicyclic or tricyclic moiety which optionally may contain 1-3 heteroatoms selected independently from O, N and S; Z is -O-, -NH-, -S-, -CH2- or a direct bond; n is 0-5; m is 0-3; R represents hydrogen, hydroxy, halogeno, cyano, nitro, trifluoromethyl, C1-3alkyl, C1-3alkoxy, C1-3alkylsulphanyl, -NRR (wherein R and R, which may be the same or different, each represents hydrogen or C1-3alkyl), or RX- (wherein X and R are as defined herein; R represents hydrogen, oxo, halogeno, hydroxy, C1-4alkoxy, C1-4alkyl, C1-4alkoxymethyl, C1-4alkanoyl, C1-4haloalkyl, cyano, amino, C2-5alkenyl, C2-5alkynyl, C1-3alkanoyloxy, nitro, C1-4alkanoylamino, C1-4alkoxycarbonyl, C1-4alkylsulphanyl, C1-4alkylsulphinyl, C1-4alkylsulphonyl, carbamoyl, N-C1-4alkylcarbamoyl, N,N-di(C1-4alkyl)carbamoyl, aminosulphonyl, N-C1-4alkylaminosulphonyl, N,N-di(C1-4alkyl)aminosulphonyl, N-(C1-4alkylsulphonyl)amino, N-(C1-4alkylsulphonyl)-N-(C1-4alkyl)amino, N,N-di(C1-4alkylsulphonyl)amino, a C3-7alkylene chain joined to two ring C carbon atoms, C1-4alkanoylaminoC1-4alkyl, carboxy or a group RX (wherein X and R are as defined herein); and salts thereof, in the manufacture of a medicament for use in the production of an antiangiogenic and/or vascular permeability reducing effect in warm-blooded animals, processes for the preparation of such compounds, pharmaceutical compositions containing a compound of formula I or a pharmaceutically acceptable salt thereof as active ingredient and compounds of formula I. The compounds of formula I and the pharmaceutically acceptable salts thereof inhibit the effects of VEGF, a property of value in the treatment of a number of disease states including cancer and rheumatoid arthritis.

Therapeutic combinations of antihypertensive and antiangiogenics agents

The invention concerns the use of a combination of an anti-angiogenic agent and an anti-hypertensive agent for use in the manufacture of a medicament for the treatment of a disease state associated with angiogenesis in a warm-blooded mammal, such as a human being. The invention also relates to pharmaceutical compositions comprising an anti-angiogenic agent and an anti-hypertensive agent, to kits thereof and to a method of treatment of a disease state associated with angiogenesis which comprises the administration of an effective amount of a combination of an anti-angiogenic agent and an anti-hypertensive agent to a warm-blooded animal, such as a human being.