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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Authors: | Malleshappa N Noolvi Harun M Patel |
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Institution: | Department of Pharmaceutical Chemistry, ASBASJSM College of Pharmacy, Bela (Ropar), 140111 Punjab, India |
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Abstract: | 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 °C, 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. |
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Keywords: | Fusion QSAR Rational design Anticancer activity |
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