Basic information Selective EGFR inhibitor Safety Supplier Related
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AZD 3759

Basic information Selective EGFR inhibitor Safety Supplier Related

AZD 3759 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)-
  • 1-PIPERAZINECARBOXYLIC ACID, 2,4-DIMETHYL-, 4-[(3-CHLORO-2-FLUOROPHENYL)AMINO]-7-METHOXY-6-QUINAZOLINYL ESTER
CAS:
1626387-80-1
MF:
C22H23ClFN5O3
MW:
459.9
EINECS:
1592732-453-0
Product Categories:
  • API
Mol File:
1626387-80-1.mol
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AZD 3759 Chemical Properties

Boiling point:
571.4±50.0 °C(Predicted)
Density 
1.358±0.06 g/cm3(Predicted)
storage temp. 
Store at -20°C
solubility 
≥23 mg/mL in DMSO; insoluble in H2O; ≥8.32 mg/mL in EtOH with ultrasonic
form 
solid
pka
6.71±0.40(Predicted)
color 
White to off-white
InChI
InChI=1S/C22H23ClFN5O3/c1-13-11-28(2)7-8-29(13)22(30)32-19-9-14-17(10-18(19)31-3)25-12-26-21(14)27-16-6-4-5-15(23)20(16)24/h4-6,9-10,12-13H,7-8,11H2,1-3H3,(H,25,26,27)/t13-/m1/s1
InChIKey
MXDSJQHFFDGFDK-CYBMUJFWSA-N
SMILES
N1(C(OC2C(OC)=CC3C(C=2)=C(NC2=CC=CC(Cl)=C2F)N=CN=3)=O)CCN(C)C[C@H]1C
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AZD 3759 Usage And Synthesis

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.

Description

AZD3759 is an EGFP inhibitor (Epidermal growth factor receptor tyrosine kinase inhibitor) with blood brain barrier (BBB) penetration. It has the potential for the treatment of non-small cell lung cancer (NSCLC), with brain metastases (BM) and leptomengingeal metastases (LM) since this type of cancer often contain a lot of activating mutations of the epidermal growth factor receptor (EGFR). It has excellent capability of penetrating the blood brain barrier to reach the central nervous system.

Uses

AZD 3759 is EGFR inhibitor. It is a potent, oral active, central nervous system-penetrant, epidermal growth factor receptor tyrosine kinase inhibitor.

Biological Activity

AZD3759 is a new, potent, oral, active central nervous system (CNS)‐penetrant EGFR inhibitor. It is mainly designed to effectively bypass the blood-brain barrier to address CNS metastasis in NSCLC patients carrying EGFR mutations, such as brain metastasis (BM) and dura mater (or pia mater, leptomeningeal metastases). AZD3759 is currently at a phase I/II research and development stage. At Km ATP concentrations, the half maximal inhibitory concentrations (IC50) were 0.3, 0.2, and 0.2 nM for wild‐type EGFR and mutated variants L858R and exon19Del, respectively. AZD3759 exhibited inhibitory effects on the proliferation of the phosphorylated (p) EGFR pathway and EGFR mutant-derived PC‐9 and H3255 cells, with IC50 of 7.7 nm and 7 nm, respectively. However, it had no inhibitory effect on the proliferation rate of H838 cells[4].

References

[1] 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.
[2] 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.
[3] 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.
[4] Qingjun Wu. “Determination and pharmacokinetic study of AZD-3759 in rat plasma by ultra performance liquid chromatography with triple quadrupole mass spectrometer.” Thoracic Cancer 9 11 (2018): 1383–1389.

AZD 3759Supplier

Jinan Chuanbei Biotechnology Co., Ltd Gold
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sales@boylechem.com