Synthesis, method optimization, anticancer activity of 2,3,7-trisubstituted Quinazoline derivatives and targeting EGFR-tyrosine kinase by rational approach: 1st Cancer Update

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• 作者：Malleshappa N. Noolvi ; ^{mnoolvi@yahoo.co.uk} ; ^{mallesh7301@rediffmail.com} ; Harun M. Patel ^{hpatel_38@yahoo.com}
• 关键词：Synthesis 3-(benzylideneamino)-7-chloro-2-phenyl quinazoline-4(3H)-one ; Fusion ; QSAR ; Rational design ; Anticancer activity
• 刊名：Arabian Journal of Chemistry
• 出版年：2013
• 出版时间：January, 2013
• 年：2013
• 卷：6
• 期：1
• 页码：35-48
• 全文大小：1476 K

文摘

A novel 3-(substituted benzylideneamino)-7-chloro-2-phenyl quinazoline-4(3H)-one (7-27) has been synthesized and characterised by IR, ¹H NMR, ¹³C NMR spectroscopy, and elemental analysis. We changed the methodology for the synthesis of 3-amino 7-chloro-2-phenyl quinazolin-4(3H)-one 6 to fusion reaction at 250 ¡ãC, instead of using solvent, to avoid the problem of ring opening, which is commonly observed while synthesizing quinazolines from benzoxazinone. NCI selected, 7-chloro-3-{[(4-chlorophenyl) methylidene] amino}-2-phenylquinazolin-4(3H)-one 12, with GI₅₀ value of ?5.59 M, TGI value of ?5.12 M, and LC₅₀ value of ?4.40 M showed remarkable activity against CNS SNB-75 Cancer cell line. Rational approach and QSAR techniques enabled the understanding of the pharmacophoric requirement for 2,3,7-tri substituted quinazoline derivatives to inhibit EGFR-tyrosine kinase as antitumor agents and could be used as an excellent framework in this field that may lead to discovery of potent anti tumor agent.