Design, synthesis, and in vitro/vivo anticancer activity of 4-substituted 7-(3-fluoro-4-methoxybenzyl)-7H-pyrrolo[2,3-d]pyrimidines

被引：2

作者：

Tsai, Pei-Yi ^{[1
]}

Hu, Gong-Siang ^{[2
]}

Huang, Po-Hsun ^{[2
]}

Jheng, Huei-Lin ^{[1
]}

Lan, Chi-Hsuan ^{[2
,3
]}

Chen, You-Sin ^{[2
,3
]}

Chang, Jia-Ming ^{[1
]}

Chuang, Shih-Hsien ^{[1
]}

Huang, Jiann-Jyh ^{[2
,3
]}

机构：

[1] Natl Biotechnol Res Pk, Dev Ctr Biotechnol, Taipei, Taiwan

[2] Natl Chiayi Univ, Dept Appl Chem, 300 Syuefu Rd, Chiayi 60004, Taiwan

[3] Natl Chiayi Univ, Training & Res Inst Food & Agr, Chiayi, Taiwan

来源：

JOURNAL OF THE CHINESE CHEMICAL SOCIETY | 2021年 / 68卷 / 09期

关键词：

anticancer; colchicine; combretastatin; ottelione A; pyrrolopyrimidine; tubulin; ENANTIOSELECTIVE TOTAL-SYNTHESIS; COMBRETASTATIN A-4 DERIVATIVES; OTTELIONE-B; ABSOLUTE-CONFIGURATION; ANTITUMOR AGENTS; (-)-OTTELIONE-B; (+)-OTTELIONE-A; INHIBITORS; DISCOVERY; REAGENTS;

D O I：

10.1002/jccs.202100100

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

In this paper, we report the design and synthesis of 4-substituted 7-(3-fluoro-4-methoxybenzyl)-7H-pyrrolo[2,3-d]pyrimidines of scaffold 6 as anticancer agents. A total of 19 derivatives of scaffold 6 bearing a C-4 alkoxy, dialkylamino, alkyl, vinyl, or phenyl substituent were synthesized and evaluated. Among them, compound 6q having a C-4 ethyl group and a benzylic methyl group showed the most potent in vitro anticancer activity, inhibiting the proliferation of Hela, MDA-MB-231, and MDA-MB-426 cancer cells at submicromolar concentrations (GI(50): 0.11-0.58 mu M). Compound 6q arrested the cell cycle of MDA-MB-231 at G(2)/M phase, and showed in vivo activity on nude mice bearing MDA-MB-231 xenografts. Compound 6q has served as an anticancer lead for further optimization.

引用

页码：1761 / 1770

页数：10

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