New Synthetic Route of Two Active Isomeric Metabolites of Erlotinib and Their Bioactivity Studies against Several Tumor Cell Lines

The synthesis and differential antiproliferative activity of two active isomeric metabolites of erlotinib were in- vestigated. This synthetic process had demonstrated to avoid the unstable 4-chloroquinazoline intermediates and long procedures. New intermediates and final compounds were identified by...

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Published inChinese journal of chemistry Vol. 29; no. 8; pp. 1709 - 1714
Main Author 李汉青 李梦瑶 李载权 李良 毕姗姗 邓晨辉 陈睿 周田彦 卢炜
Format Journal Article
LanguageEnglish
Published Weinheim WILEY-VCH Verlag 01.08.2011
WILEY‐VCH Verlag
Wiley
Wiley Subscription Services, Inc
Subjects
active metabolites
antiproliferation
biological activity
Chemistry
Chemistry, Multidisciplinary
epidermal growth factor receptor
erlotinib hydrochloride
Metabolites
Physical Sciences
Science & Technology
代谢产物
合成路线
同分异构体
增殖活性
生物活性
肿瘤细胞株
酪氨酸激酶
高效液相色谱
GEFITINIB
ACTIVATION
biological activity
epidermal growth factor receptor
ACUTE MYELOGENOUS LEUKEMIA
EGFR
DISCOVERY
SMALL-MOLECULE INHIBITOR
TYROSINE KINASE INHIBITORS
GROWTH-FACTOR RECEPTOR
erlotinib hydrochloride
active metabolites
PHARMACOKINETICS
FLT3 ANTAGONIST
antiproliferation
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Summary:The synthesis and differential antiproliferative activity of two active isomeric metabolites of erlotinib were in- vestigated. This synthetic process had demonstrated to avoid the unstable 4-chloroquinazoline intermediates and long procedures. New intermediates and final compounds were identified by IH NMR, 13C NMR and ESI-TOF MS, and their purities were determined by high performance liquid chromatography. In vitro proliferative assay indi- cated that these two metabolites possessed antiproliferative activity against some conventional tumor cell lines and EGFR tyrosine kinase over-expression tumor cell lines as compared to erlotinib control, and their antitumor activity in cellular level was first reported here.
Bibliography:31-1547/O6
erlotinib hydrochloride, epidermal growth factor receptor, active metabolites, biological activity, anti-proliferation
The synthesis and differential antiproliferative activity of two active isomeric metabolites of erlotinib were in- vestigated. This synthetic process had demonstrated to avoid the unstable 4-chloroquinazoline intermediates and long procedures. New intermediates and final compounds were identified by IH NMR, 13C NMR and ESI-TOF MS, and their purities were determined by high performance liquid chromatography. In vitro proliferative assay indi- cated that these two metabolites possessed antiproliferative activity against some conventional tumor cell lines and EGFR tyrosine kinase over-expression tumor cell lines as compared to erlotinib control, and their antitumor activity in cellular level was first reported here.
ark:/67375/WNG-JGP21CSL-N
National Integrity Innovational Technology Platform of New Drug and Development - No. 2009ZX09301-010
istex:51DC736F576BEAABC412A8D3586C6AAB37FA056A
ArticleID:CJOC201180305
National Fund for Talent training in Basic Science
ISSN:1001-604X
1614-7065
DOI:10.1002/cjoc.201180305