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Updated: May 8, 2026

Facile Preparation of 4-Substituted Quinazoline Derivatives
Published on: February 15, 2016
Design, synthesis, and structure-activity relationships of novel 6,7-disubstituted-4-phenoxyquinoline derivatives as
Qidong Tang1, Yanfang Zhao, Xinming Du
1Key Laboratory of Structure-Based Drug Design and Discovery (Shenyang Pharmaceutical University), Ministry of Education, 103 Wenhua Road, Shenhe District, Shenyang 110016, PR China.
Abstract:
Two series of quinoline derivatives bearing the pyridine/pyrimidine scaffold were synthesized, and evaluated for their c-Met kinase inhibitory activity and antiproliferative activity against 5 cancer cell lines (HT-29, H460, MKN-45, A549, and U87MG) were evaluated in vitro. Most compounds showed moderate to excellent potency, and compared to foretinib, the most promising analog 18b (c-Met half-maximal inhibitory concentration [IC₅₀] = 1.39 nM) showed a 7.3-fold increase in activity against HT-29 cell line in vitro. Structure-activity relationship studies indicated that regulation of the electron density on the pyridine/pyrimidine ring to a proper degree was a key factor in improving the antitumor activity.
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