388082-81-3

Basic information

• Product Name: GW583340 DIHYDROCHLORIDE
• Synonyms: 4-[3-CHLORO-4-[(3-FLUOROPHENYL)METHOXY]P;4-[3-Chloro-4-[(3-fluorophenyl)methoxy]phenylamino]-6-[2-[[2-(methylsulfonyl)ethyl]aminomethyl]-4-thiazolyl]quinazoline dihydrochloride;N-[3-Chloro-4-[(3-fluorophenyl)methoxy]phenyl]-6-[2-[[[2-(methylsulfonyl)ethyl]amino]methyl]-4-thiazolyl]-4-quinazolinaminedihydrochloride
• CAS NO: 388082-81-3
• Molecular Formula: C₂₈H₂₅ClFN₅O₃S₂
• Molecular Weight: 671.042
• Mol File: 388082-81-3.mol

Chemical Properties

• Melting Point: 259.8-262.4 °C(lit.)
• Boiling Point: 816.5°C at 760 mmHg
• Flash Point: 447.6°C
• Appearance: /solid
• Vapor Pressure: 2.9E-27mmHg at 25°C
• Storage Temp.: 2-8°C
• Solubility: DMSO: 9 mg/mL
• CAS DataBase Reference: GW583340 DIHYDROCHLORIDE(CAS DataBase Reference)
• NIST Chemistry Reference: GW583340 DIHYDROCHLORIDE(388082-81-3)
• EPA Substance Registry System: GW583340 DIHYDROCHLORIDE(388082-81-3)

Safety Data

• Hazard Codes: Xi
• Statements: 36/37/38
• Safety Statements: 26-36
• WGK Germany: 3
• Hazardous Substances Data: 388082-81-3(Hazardous Substances Data)

Usage

Biological Activity

Potent dual EGFR/ErbB2 tyrosine kinase inhibitor (IC 50 values are 0.01 and 0.014 μ M respectively). Selectively inhibits growth of human tumor cells overexpressing EGFR and ErbB2: IC 50 values are 0.11 μ M for inhibition of HN5, N87 and BT474 tumor cell lines vs. > 30 μ M for inhibition of non-tumor cell line HFF. In vivo, inhibits tumor growth by ~ 80% in a murine xenograft model following oral administration.

InChI:InChI=1/C28H25ClFN5O3S2.2ClH/c1-40(36,37)10-9-31-14-27-35-25(16-39-27)19-5-7-24-22(12-19)28(33-17-32-24)34-21-6-8-26(23(29)13-21)38-15-18-3-2-4-20(30)11-18;;/h2-8,11-13,16-17,31H,9-10,14-15H2,1H3,(H,32,33,34);2*1H

Upstream product

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Relevant articles and documents

CANCER TREATMENT METHOD

A method of treating cancer is described including administration of a pyrimidine derivative and a quinazoline derivative as well as a pharmaceutical composition including the same.

Discovery and biological evaluation of potent dual ErbB-2/EGFR tyrosine kinase inhibitors: 6-Thiazolylquinazolines

We have identified a novel class of 6-thiazolylquinazolines as potent and selective inhibitors of both ErbB-2 and EGFR tyrosine kinase activity, with IC50 values in the nanomolar range. These compounds inhibited the growth of both EGFR (HN5) and ErbB-2 (BT474) over-expressing human tumor cell lines in vitro. Using xenograft models of the same cell lines, we found that the compounds given orally inhibited in vivo tumor growth significantly compared with control animals.

Heterocyclic compounds

The present invention relates to substituted heteroaromatic compounds, methods for their preparation, pharmaceutical compositions containing them and their use in medicine. Specifically, the invention relates to quinazoline derivatives useful in treating disorders mediated by protein tyrosine kinase activity, in particular erbB-2 and/or EGFR activity.