Anticancer drugs Treatment of advanced (non-small cell lung cancer) NSCLC Preparation method
ChemicalBook > CAS DataBase List > Vandetanib

Vandetanib

Anticancer drugs Treatment of advanced (non-small cell lung cancer) NSCLC Preparation method
Product Name
Vandetanib
CAS No.
443913-73-3
Chemical Name
Vandetanib
Synonyms
CS-97;D6474;Zactima;ZD 6474;AZD6474;Vetanib;VANDETANIB;Vandetanib base;ZD6474; ZACTIMA;ZD6474;AZD-6474
CBNumber
CB01011762
Molecular Formula
C22H24BrFN4O2
Formula Weight
475.35
MOL File
443913-73-3.mol
More
Less

Vandetanib Property

Melting point:
240-2430C
Boiling point:
538.2±50.0 °C(Predicted)
Density 
1.406
Flash point:
279.3℃
storage temp. 
Keep in dark place,Inert atmosphere,Store in freezer, under -20°C
solubility 
Soluble in DMSO (30 mg/ml); Ethanol (10 mg/ml with warming)
pka
8.92±0.10(Predicted)
form 
solid
color 
White to off-white
Stability:
Stable for 2 years from date of purchase as supplied. Solutions in DMSO or ethanol may be stored at -20°C for up to 1 month.
CAS DataBase Reference
443913-73-3
More
Less

Safety

Safety Statements 
24/25
HS Code 
29333220
Hazardous Substances Data
443913-73-3(Hazardous Substances Data)
More
Less

Hazard and Precautionary Statements (GHS)

Symbol(GHS)
Signal word
Danger
Hazard statements

H227Combustible liquid

H302Harmful if swallowed

H312Harmful in contact with skin

H315Causes skin irritation

H318Causes serious eye damage

H332Harmful if inhaled

H335May cause respiratory irritation

H410Very toxic to aquatic life with long lasting effects

Precautionary statements

P210Keep away from heat/sparks/open flames/hot surfaces. — No smoking.

P261Avoid breathing dust/fume/gas/mist/vapours/spray.

P264Wash hands thoroughly after handling.

P264Wash skin thouroughly after handling.

P270Do not eat, drink or smoke when using this product.

P271Use only outdoors or in a well-ventilated area.

P273Avoid release to the environment.

P280Wear protective gloves/protective clothing/eye protection/face protection.

P302+P352IF ON SKIN: wash with plenty of soap and water.

P304+P340IF INHALED: Remove victim to fresh air and Keep at rest in a position comfortable for breathing.

P305+P351+P338IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continuerinsing.

P310Immediately call a POISON CENTER or doctor/physician.

P330Rinse mouth.

P332+P313IF SKIN irritation occurs: Get medical advice/attention.

P362Take off contaminated clothing and wash before reuse.

P370+P378In case of fire: Use … for extinction.

P403+P233Store in a well-ventilated place. Keep container tightly closed.

P403+P235Store in a well-ventilated place. Keep cool.

P405Store locked up.

P501Dispose of contents/container to..…

More
Less

N-Bromosuccinimide Price

Cayman Chemical
Product number
14706
Product name
Vandetanib
Purity
≥98%
Packaging
5mg
Price
$32
Updated
2023/01/06
Cayman Chemical
Product number
14706
Product name
Vandetanib
Purity
≥98%
Packaging
10mg
Price
$57
Updated
2023/01/06
Cayman Chemical
Product number
14706
Product name
Vandetanib
Purity
≥98%
Packaging
25mg
Price
$95
Updated
2023/01/06
Cayman Chemical
Product number
14706
Product name
Vandetanib
Purity
≥98%
Packaging
100mg
Price
$275
Updated
2023/01/06
Usbiological
Product number
291899
Product name
Vandetanib
Packaging
100mg
Price
$319
Updated
2021/12/16
More
Less

Vandetanib Chemical Properties,Usage,Production

Anticancer drugs

Vandetanib is a kind of small molecule multi-targeted tyrosine kinase inhibitor studied and developed by the British AstraZeneca Company. In April 2011, it was approved the US FDA for entering into market under the trade name Zactima. The drug, as a tablet, can be applied to the treatment of advanced medullary thyroid cancer of adult patients.
Vandetanib is a multi-targeted tyrosine kinase inhibitor, and belongs to the Anilinoquinazoline compounds, called "second generation Iressa”. It not only acts on the tumor cells, EGFR, VEGFR and RET tyrosine kinases, but can also inhibit other kind of tyrosine kinases and serine/threonine kinases. Vandetanib is the first approved drugs approved for treatment of medullary thyroid carcinoma. It is suitable for treating unresectable, locally advanced or metastatic-symptoms or progressive medullary thyroid carcinoma. A randomized, placebo-controlled clinical trial results have showed that vandetanib can significantly delay the progression time of locally advanced or metastatic medullary thyroid cancer. The recommended daily dose is 300 mg (oral), when the patient exhibits tolerance to drugs or being not able to tolerate the toxicity, they should stop treatment immediately. Those most common adverse reactions of this medicine include diarrhea, rash, acne, nausea, hypertension, headache, fatigue, loss of appetite and abdominal pain. The adverse reactions is dose-related; at <300 mg/d, the patient has a well tolerance with the maximum tolerated dose (MTD) being 300mg. There are many kinds disease types contained in the Ⅱ phase clinical study. The NSCLC clinical trials of vandetanib are currently under way for China.
British AstraZeneca Company, in May 2001 and October 2001, respectively, had obtained preferential access to the world's patent (WO2001032651, WO 2001074360) and applied corresponding protection on the formula, synthesis methods and pharmaceutical compositions of these compounds (including bonus salt). Vandetanib can inhibit the development of medullary thyroid carcinoma, and is the first FDA-approved drug for the treatment of the disease and will provide support for the treatment of advanced medullary thyroid cancer in adult patients.
The above information is edited by the chemicalbook of Dai Xiongfeng.

Treatment of advanced (non-small cell lung cancer) NSCLC

A study published in the [Journal of Clinical Oncology] have showed that compared with gefitinib which only has inhibitory effect on EGFR, vandetanib can effectively extend the progression-free survival period of the non-small cell lung cancer (NSCLC) patients.
In this phase II clinical trial conducted by doctors Ronald B. Natale from Los Angeles Cedars-Sinai Cancer Center, clinical study compared the treatment efficacy of vandetanib (300 mg/d) and gefitinib (250mg/d) on 168 cases of NSCLC patients who had been subject to failing first-line or second-line chemotherapy. Compared with gefitinib, vandetanib significantly increased efficiency and prolonged the progression-free survival, period respectively, by 8% and 1%, 11.9 weeks and 8.1 weeks, (P = 0.011). In clinical trials, if there is progression of the disease or if the patient can’t tolerate the toxicity, they allowed the patients to change the treatment regimen. Experimental results had shown that using gefitinib for replacing vandetanib in patients gave a disease control rate of 14% while using vandetanib to replace gefitinib gave a disease control rate of 32%. The overall survival period in the case of vandetanib → gefitinib was 6.1 months while it was 7.4 months in the cases of gefitinib → vandetanib.

Preparation method

Use 4-hydroxy-3-methoxy-benzoic acid ethyl ester as a starting material, go through substitution, reduction, nitrification, reduction, cyclization aromatization to give 4-chloro-6-methoxy--7-(N-methyl piperidin-4-ylmethoxy) quinazoline (A), A was then reacted with 4-bromo-2-aniline to obtain the targeted compound vandetanib.

Description

In April 2011, the U.S. FDA approved vandetanib (ZD6474) for the treatment of symptomatic or progressive medullary thyroid cancer (MTC) in adult patients with inoperable advanced ormetastatic disease. Vandetanib inhibits KDR/VEGFR2, VEGFR3, EGFR, and RET kinases with IC50's of 40, 110, 500, and <100 nM, respectively. In athymic mice bearing MTC tumors, a 14.5-fold reduction of tumor volume was observed after 45 days of treatment with vandetanib at 50 mg/kg/day. The decrease in tumor volume was accompanied by decreases in mitotic index (Ki67) and tumor angiogenesis in treated xenografts. Key steps in the synthesis of vandetanib include the displacement of the chlorine atom from 7-benzyloxy-4-chloro-6-methoxyquinazoline with 4-bromo-2- fluoroaniline under acidic conditions in a protic solvent and a Mitsunobu reaction of a N-protected piperidine alcohol with a phenol.

Chemical Properties

Yellow Solid

Originator

Astra Zeneca (United Kingdom)

Uses

Vandetanib (Zactima, ZD6474) is a potent inhibitor of VEGFR2 with IC50 of 40 nM.

Uses

Vandetanib (ZD6474) is a potent inhibitor of VEGFR2 with IC50 of 40 nM

Uses

Vandetanib is a once-daily oral inhibitor of vascular endothelial growth factor receptor-2 and epidermal growth factor receptor kinase activity. The activity of Vandetanib plus Docetaxel was assessed in patients with previously treated non-small-cell lung cancer (NSCLC).

Uses

Vandetanib is a broad spectrum, orally available kinase inhibitor that targets primarily tyrosine kinases, including vascular endothelial growth factor receptor (VEGFR) and epidermal growth factor receptor (EGFR), with IC50 values in the nanomolar range. It also potently blocks non-receptor tyrosine kinases, including ABL, RET, and SRC, as well as several serine/threonine kinases. Primarily because of its effects on receptor tyrosine kinases like VEGFR and EGFR, vandetanib inhibits angiogenesis, cell growth, and metastasis and is effective against certain forms of cancer.[Cayman Chemical]

brand name

Zactima (AstraZeneca);Caprelsa.

Clinical Use

Vandetanib, an oral VEGF, EGF, and RET receptor tyrosine kinase inhibitor, was developed by AstraZeneca for the treatment of symptomatic or aggressive medullary thyroid cancer (MTC) in patients with advanced or metastatic disease. This is the first drug approved for the treatment of MTC. Trials for other cancer indications such as small-cell lung cancer (SCLC), breast cancer, head and neck cancer, colorectal cancer, hormone-resistant prostate cancer, and papillary thyroid cancer are currently being explored. While AstraZeneca had previously developed ZD-4190 which displays similar efficacy and pharmacokinetic profile to vandetanib, vandetanib exhibited significantly improved solubility.

Synthesis

Vandetanib contains a 4-anilinoquinazoline scaffold similar to other EGFR inhibitors, and the synthesis described below is based on a recent patent (Scheme).


Commercially available vanillic acid (262) was treated with benzyl bromide, DIPEA and Et3N to give ethereal ester 263 in 93% yield. Arene 263 was then subjected to nitration conditions to provide nitroarene 264 in 86% yield, which underwent immediate reduction with sodium dithionite in acetonitrile and water to give aniline 265 in 92% yield. Aniline 265 was then treated with foramidine acetate in isobutanol which affected an intramolecular cyclization reaction, giving rise to dihydroquinazolin-4-one 266 in 98% yield. Heterocycle 266 was treated with phosphorous oxychloride and the resulting quinazoline chloride was subsequently reacted with 4-bromo-2-fluoroaniline 267 and trifluoroacetic acid to give hydroxyaniline 268 in 90% for the three-step sequence. Phenolic azacycle 268 was then alkylated with sulfonate 269 to furnish piperidine 270 in 77% yield. Subsequent treatment with formic acid and aqueous formaldehyde under elevated temperatures gave vandetanib (XXIII) in 91% yield.

Drug interactions

Potentially hazardous interactions with other drugs
Analgesics: possibly increased risk of ventricular arrhythmias with methadone - avoid.
Anti-arrhythmics: possibly increased risk of ventricular arrhythmias with amiodarone or disopyramide - avoid.
Antibacterials: possibly increased risk of ventricular arrhythmias with parenteral erythromycin and moxifloxacin - avoid; concentration reduced by rifampicin - avoid.
Antihistamines: possibly increased risk of ventricular arrhythmias with mizolastine - avoid.
Antimalarials: possibly increased risk of ventricular arrhythmias with artemether with lumefantrine - avoid.
Antipsychotics: possibly increased risk of ventricular arrhythmias with amisulpiride, chlorpromazine, haloperidol, pimozide, sulpiride and zuclopenthixol - avoid; avoid concomitant use with clozapine, risk of agranulocytosis.
Beta-blockers: possibly increased risk of ventricular arrhythmias with sotalol - avoid.
Cytotoxics: possibly increased risk of ventricular arrhythmias with arsenic trioxide - avoid.
Hormone antagonist: possibly increased risk of ventricular arrhythmias with toremifene - avoid.
5HT3 -receptor antagonists: possibly increased risk of ventricular arrhythmias with ondansetron - avoid.
Pentamidine: possibly increased risk of ventricular arrhythmias - avoid.

Metabolism

N-desmethyl-vandetanib is primarily produced by CYP3A4, and vandetanib-N-oxide is primarily produced by flavin-containing monooxygenase enzymes FMO1 and FMO3.
Unchanged vandentanib and metabolites vandetanib N-oxide and N-desmethyl vandetanib were detected in plasma, urine (25
%) and faeces (44
%).

References

Wedge et al. (2002), ZD6474 inhibits vascular endothelial growth factor signaling, angiogenesis and tumor growth following oral administration; Cancer Res., 62 4645 Ciardiello et al. (2003), Antitumor effects of ZD6474, a small molecule vascular endothelial growth factor receptor tyrosine kinase inhibitor, with additional activity against epidermal growth factor receptor tyrosine kinase; Clin. Cancer Res., 9 1546 Herbst et al. (2007), Vandetanib (ZD6474): an orally available receptor tyrosine kinase inhibitor that selectively targets pathways critical for tumor growth and angiogenesis; Expert Opin. Investig. Drugs, 16 239

Vandetanib Preparation Products And Raw materials

Raw materials

Preparation Products

More
Less

Vandetanib Suppliers

Hefei TianRui Pharmaceutical Chemistry Co., Ltd.
Tel
0551-68933033 13956024211
Fax
0551-68935833
Email
trchem@163.com
Country
China
ProdList
96
Advantage
58
Zhongshan Haihong Medicine Co. Ltd
Tel
0760-86925768 18824993998
Fax
0760-86925770
Email
seas168@126.com
Country
China
ProdList
60
Advantage
58
Shanghai Kuanghao Chemistry Technology Co., Ltd.
Tel
021-37285271 15900820856
Fax
021-37285512
Email
83219210@qq.com
Country
China
ProdList
83
Advantage
57
Hubei Dibai Chemical Co., Ltd.
Tel
027-87058617 15872383390
Fax
027-87058617
Email
hbdibo@163.com
Country
China
ProdList
891
Advantage
58
Xi 'an Xinlu Biological Technology Co. LTD
Tel
13259841664
Email
1364569456@qq.com
Country
China
ProdList
31
Advantage
58
Hubei Changao Pharmaceutical Co., Ltd
Tel
13419508972
Email
1077975541@qq.com
Country
China
ProdList
304
Advantage
58
Shanghai Boyle Chemical Co., Ltd.
Tel
Fax
86-21-57758967
Email
sales@boylechem.com
Country
China
ProdList
2923
Advantage
55
J & K SCIENTIFIC LTD.
Tel
010-82848833 400-666-7788
Fax
86-10-82849933
Email
jkinfo@jkchemical.com
Country
China
ProdList
96815
Advantage
76
Chembest Research Laboratories Limited
Tel
021-20908456
Fax
021-58180499
Email
sales@BioChemBest.com
Country
China
ProdList
6002
Advantage
61
Carbott PharmTech Inc.
Tel
0535-6385396
Fax
+86 (535) 638-9971
Email
info@carbottpharm.com
Country
China
ProdList
776
Advantage
56
More
Less

View Lastest Price from Vandetanib manufacturers

WUHAN FORTUNA CHEMICAL CO., LTD
Product
Vandetanib 443913-73-3
Price
US $0.00/KG
Min. Order
1KG
Purity
98%min
Supply Ability
30tons/month
Release date
2023-01-17
Hong Kong Tiansheng New Material Trading Co., Ltd
Product
Vandetanib 443913-73-3
Price
US $10.99/KG
Min. Order
1KG
Purity
99%
Supply Ability
100KG
Release date
2021-12-24
Hong Kong Tiansheng New Material Trading Co., Ltd
Product
Vandetanib 443913-73-3
Price
US $18.00/Kg/Bag
Min. Order
1Kg/Bag
Purity
99%
Supply Ability
20kg
Release date
2022-01-10

443913-73-3, Vandetanib Related Search:


  • 7-((4-aminocyclohexyl)methoxy)-N-(4-bromo-2-fluorophenyl)-6-methoxyquinazolin-4-amine
  • Vandetanib(Zactima),ZD6474
  • Vandetanib(ZactiMa,AZD6474)
  • Vandetanib base
  • N-(4-BroMo-2-fluorophenyl)-6-Methoxy-7-[(1-Methylpiperidin-4-yl)Methoxy]-4-aMino-quinazoline
  • Vandetanib (ZactiMa)
  • ZD6474; ZACTIMA
  • VANDETANIB
  • 4-Quinazolinamine, N-(4-bromo-2-fluorophenyl)-6-methoxy-7-[(1-methyl-4-piperidinyl)methoxy]-
  • Vandetanib for research
  • 4-(4-Bromo-2-fluoroanilino)-6-methoxy- 7-[(1-methylpiperidin-4-yl)methoxy]quinazoline
  • N-(4-Bromo-2-fluorophenyl)-6-methoxy-7-[(1-methyl-4-piperidinyl)methoxy]-4-quinazolinamine
  • Zactima
  • ZD 6474
  • ZD6474;AZD-6474
  • Vandetanib (ZD6474, Zactima)
  • CS-97
  • Vandetanib, >=98%
  • 4-(4-Bromo-2-fluoroanilino)-6-methoxy-7-[(1-methylpiperidin-4-yl)methoxy]quinazoline Vandetanib (Zactima)
  • Vandetanib 4-(4-Bromo-2-fluoroanilino)-6-methoxy-7-[(1-methylpiperidin-4-yl)methoxy]quinazoline
  • AZD6474
  • Vandetanib(AZD6474)
  • ZD6474;ZD-6474;ZD 6474
  • D6474
  • 4-[(4-Bromo-2-fluorophenyl)amino]-6-methoxy-7-[(1-methyl-4-piperidyl)methoxy]quinazoline
  • Vandetanib USP/EP/BP
  • Vetanib
  • 443913-73-3
  • 443913-73-4
  • 913-73-3
  • C22H24BrFN4O2
  • ZD6474
  • API
  • API
  • Pharmaceutical intermediate
  • Aromatics
  • Heterocycles
  • Inhibitors
  • Intermediates & Fine Chemicals
  • Pharmaceuticals
  • Aromatics Compounds