2. Academic Validation
  3. Synthesis and antiproliferative activity of 6,7-disubstituted-4-phenoxyquinoline derivatives bearing the 2-oxo-4-chloro-1,2-dihydroquinoline-3-carboxamide moiety

Synthesis and antiproliferative activity of 6,7-disubstituted-4-phenoxyquinoline derivatives bearing the 2-oxo-4-chloro-1,2-dihydroquinoline-3-carboxamide moiety

  • Bioorg Med Chem Lett. 2016 Apr 1;26(7):1794-8. doi: 10.1016/j.bmcl.2016.02.037.
Qidong Tang 1,  Xin Zhai 2,  Yayi Tu 3,  Ping Wang 3,  Linxiao Wang 3,  Chunjiang Wu 3,  Wenhui Wang 3,  Hongbo Xie 4,  Ping Gong 2,  Pengwu Zheng 5
Affiliations

Affiliations

  • 1 School of Pharmacy, Jiangxi Science and Technology Normal University, Nanchang, Jiangxi 330013, PR China; Key Laboratory of Structure-Based Drug Design and Discovery of Ministry of Education, School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, Shenyang 110016, PR China. Electronic address: tangqidongcn@126.com.
  • 2 Key Laboratory of Structure-Based Drug Design and Discovery of Ministry of Education, School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, Shenyang 110016, PR China.
  • 3 School of Pharmacy, Jiangxi Science and Technology Normal University, Nanchang, Jiangxi 330013, PR China.
  • 4 College of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150081, PR China.
  • 5 School of Pharmacy, Jiangxi Science and Technology Normal University, Nanchang, Jiangxi 330013, PR China. Electronic address: zhengpw@126.com.
PMID: 26944614 DOI: 10.1016/j.bmcl.2016.02.037
Abstract

A series of 6,7-disubstituted-4-phenoxyquinoline derivatives bearing the 2-oxo-4-chloro-1,2-dihydroquinoline-3-carboxamide moiety were synthesized, and evaluated for their antiproliferative activity against 5 Cancer cell lines (H460, HT-29, MKN-45, A549, and U87MG). Most compounds showed moderate to excellent potency, and compared to foretinib, the most promising analog 42 (c-Met/Flt-3 IC50=1.21/2.15nM) showed a 6.1-fold increase in activity against H460 cell line in vitro. The enzymatic assays (c-Met, VEGFR-2, Flt-3, PDGFR-β, c-Kit, and EGFR) of compound 42 were evaluated in vitro. Docking analysis showed that compound 42 could form three hydrogen bonds with c-Met. Structure-activity relationship studies indicated that a more water-soluble cyclic tertiary amine and electron-withdrawing groups at 4-position of the phenyl ring contribute to the antitumour activity.

Keywords

2-Oxo-4-chloro-1,2-dihydroquinoline; Antiproliferative activity; Quinoline derivatives; Synthesis; c-Met.

Figures
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z