1626387-80-1

Basic information

• Product Name: AZD 3759
• Synonyms: AZD 3759;AZD3759;AZD-3759;(2R)-2,4-Dimethyl-1-piperazinecarboxylic acid 4-[(3-chloro-2-fluorophenyl)amino]-7-methoxy-6-quinazolinyl ester;HY-18750;azd3579;1-Piperazinecarboxylic acid, 2,4-dimethyl-, 4-[(3-chloro-2-fluorophenyl)amino]-7-methoxy-6-quinazolinyl ester, (2R)-;4-((3-Chloro-2-fluorophenyl)amino)-7-methoxyquinazolin-6-yl (2R)-2,4-dimethylpiperazine-1-carb
• CAS NO: 1626387-80-1
• Molecular Formula: C22H23ClFN5O3
• Molecular Weight: 459.91
• EINECS: 1592732-453-0
• Product Categories: API
• Mol File: 1626387-80-1.mol
• Article Data: 8

Chemical Properties

• Boiling Point: 571.4±50.0 °C(Predicted)
• Appearance: /
• Density: 1.358±0.06 g/cm3(Predicted)
• Solubility: ≥23 mg/mL in DMSO; insoluble in H2O; ≥8.32 mg/mL in EtOH with ultrasonic
• PKA: 6.71±0.40(Predicted)
• CAS DataBase Reference: AZD 3759(CAS DataBase Reference)
• NIST Chemistry Reference: AZD 3759(1626387-80-1)
• EPA Substance Registry System: AZD 3759(1626387-80-1)

Safety Data

• Hazardous Substances Data: 1626387-80-1(Hazardous Substances Data)

Usage

Description

AZD3759 is an EGFR inhibitor (Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor) with the ability to penetrate the blood-brain barrier (BBB). It is a potent, orally active, and central nervous system-penetrant drug that has the potential for the treatment of non-small cell lung cancer (NSCLC), particularly in cases with brain metastases (BM) and leptomeningeal metastases (LM). This is due to the high prevalence of activating mutations of the epidermal growth factor receptor (EGFR) in such cancers. AZD3759's excellent capability of penetrating the BBB allows it to reach the central nervous system, making it a promising pharmaceutical candidate for targeted cancer therapy.

Uses

Used in Oncology:
AZD3759 is used as an EGFR inhibitor for the treatment of non-small cell lung cancer (NSCLC), particularly in cases with brain metastases (BM) and leptomeningeal metastases (LM). Its ability to penetrate the blood-brain barrier enables it to effectively target and inhibit the epidermal growth factor receptor, which is often mutated in these types of cancers, leading to improved treatment outcomes and potentially better patient prognosis.
Used in Drug Development:
AZD3759 is used as a research tool in the development of novel cancer therapies targeting the epidermal growth factor receptor (EGFR). Its unique properties, such as oral activity and central nervous system penetration, make it a valuable compound for studying the mechanisms of EGFR inhibition and its potential applications in various cancer types, including those with brain metastases.
Used in Pharmaceutical Research:
AZD3759 is used as a starting point for the development of new drugs with improved pharmacological properties, such as enhanced efficacy, reduced side effects, or targeted delivery. Its ability to penetrate the blood-brain barrier and inhibit EGFR makes it an attractive candidate for further research and development in the pharmaceutical industry, potentially leading to the creation of more effective treatments for various types of cancer.

Selective EGFR inhibitor

AZD3759 is a selective EGFR inhibitor that can fully penetrate the blood-brain barrier (BBB), with equal free concentrations in the blood, cerebrospinal fluid, and brain tissue. Treatment with AZD3759 causes tumor regression in subcutaneous xenograft, leptomeningeal metastasis (LM), and brain metastasis (BM) lung cancer models and prevents the development of BM in nude mice.

References

Zeng, Qingbei, et al. "Discovery and Evaluation of Clinical Candidate AZD3759, a Potent, Oral Active, Central Nervous System-Penetrant, Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor (EGFR TKI)." Journal of Medicinal Chemistry 58.20(2015):8200. Yang, Zhenfan, et al. "Abstract LB-217: Antitumor activities of AZD3759, a novel EGFR inhibitor with excellent penetration across central nervous system (CNS), in preclinical animal models." Cancer Research 76.14 Supplement(2016):LB-217-LB-217. Xiong, S., et al. "Determination of AZD3759 in rat plasma and brain tissue by LC-MS/MS and its application in pharmacokinetic and brain distribution studies." Journal of Pharmaceutical & Biomedical Analysis140(2017):362-366.

Upstream product

• 179688-52-9 4,6-dihydroxy-7-methoxyquinazoline 
• 179688-53-0 (4-hydroxy-7-methoxyquinazolin-6-yl) acetate 
• 230955-75-6 6-acetoxy-4-chloro-7-methoxyquinazoline 
• 740081-22-5 4-[(3-chloro-2-fluorophenyl)amino]-7-methoxyquinazolin-6-yl acetate 
• 612501-52-7 4-(3-chloro-2-fluoroanilino)-6-hydroxy-7-methoxyquinazoline 
• 4998-07-6 4,5-dimethoxy-2-nitro-benzoic acid 
• 163765-44-4 (R)-tert-butyl 3-methylpiperazine-1-carboxylate 
• 438050-54-5 (3R)-4-(chlorocarbonyl)-3-methylpiperazine-1-carboxylic acid tert-butyl ester 
• 50-00-0 formaldehyd 
• 31839-20-0 5-hydroxy-4-methoxy-2-nitrobenzoic acid 
• 31839-21-1 2-amino-5-hydroxy-4-methoxybenzoic acid 
• 2106-04-9 3-chloro-2-fluoroaniline 
• 612501-80-1 4-[(3-chloro-2-fluorophenyl)amino]-7-methoxyquinazolin-6-yl acetate monohydrochloride 
• 75336-86-6 (2R)-methylpiperazine 

Downstream Products

• 1626387-81-2 4-[(3-chloro-2-fluorophenyl)amino]-7-methoxyquinazolin-6-yl (2R)-2,4-dimethylpiperazine-1-carboxylate hydrochloride 

Relevant articles and documents

Preparation method of lung cancer drug AZD3759

The present invention provides a method for preparing a lung cancer drug AZD3759. Using compounds of formula VIII and compounds of formula V. as raw materials, after hydrolysis reaction, condensation reaction, ammonization reaction, acidolysis reaction, methylation reaction, compound of formula I AZD3759 was obtained. The method has a novel route, simple response, environmental friendliness and high yield, which is suitable for industrial large-scale production.

Preparation method of tyrosine kinase inhibitor AZD3759

The invention provides a preparation method of a tyrosine kinase inhibitor AZD3759, and relates to the field of medicinal chemistry. The preparation method comprises the following steps: by taking 3,4-dihydro-7-methoxy-4-oxoquinazoline-6-alcohol acetate as a raw material, carrying out a chlorination reaction and a hydrolysis reaction to obtain 4-chloro-7-methoxyquinazoline-6-alcohol (a compound 3); taking (R)-(-)-2-methylpiperazine as a raw material, and obtaining (R)-4-chlorocarbonyl-3-tert-butyl formate (compound 6) through a nucleophilic addition-elimination reaction and a chloroformylation reaction; carrying out an esterification reaction on the compound 3 and the compound 6 to obtain a compound 7; carrying out a Boc removal reaction and a methylation reaction on the compound 7 to obtain a compound 9; and carrying out alkylation reaction on the compound 9 and 2-fluoro-3-chloroaniline to obtain AZD3759. The method has the advantages of cheap and accessible raw materials and lower cost; sodium cyanoborohydride is not used in the reaction process, so that the method is more environment-friendly and is beneficial to industrial large-scale production.

Novel quinazoline inhibitor

The present invention relates to a novel quinazoline inhibitor, and disclose a compound represented by a formula (I) and a pharmaceutically acceptable salt thereof, a method for preparing the compoundrepresented by the formula (I) and the pharmaceutically acceptable salt thereof, a pharmaceutical composition containing a therapeutically effective amount of the compound represented by the formula(I) or the pharmaceutically acceptable salt thereof, and uses of the compound represented by the formula (I) and the pharmaceutically acceptable salt thereof. The formula (I) is defined in the specification.