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

共 50 条

[31] Synthesis, spectral characterization and in vitro anti-inflammatory activity of 4-substituted amino-5,6,7,8-tetrahydrobenzothiopheno[2,3-d]pyrimidines
Jagtap, V. A.
Agasimundin, Y. S.
JOURNAL OF THE INDIAN CHEMICAL SOCIETY, 2014, 91 (03) : 545 - 548
[32] PHOSPHORUS PENTOXIDE IN ORGANIC-SYNTHESIS .12. SYNTHESIS OF "7H-PYRROLO[2,3-D]PYRIMIDIN-4-AMINES
JORGENSEN, A
GIRGIS, NS
PEDERSEN, EB
LIEBIGS ANNALEN DER CHEMIE, 1985, (01): : 142 - 148
[33] 7-(5-Methylsulfanyl-β-D-erythrofuranosyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine monohydrate (MT-tubercidin•H2O)
Gainsford, Graeme J.
Froehlich, Richard F. G.
Evans, Gary B.
ACTA CRYSTALLOGRAPHICA SECTION E-STRUCTURE REPORTS ONLINE, 2010, 66 : O1688 - U457
[34] An improved synthesis of 4-chloro-7H-pyrrolo[2,3-d]pyrimidine
Zhang, Yu-Liu
Xu, Cheng-Tao
Liu, Ting
Zhu, Yong
Luo, Yu
CHEMISTRY OF HETEROCYCLIC COMPOUNDS, 2018, 54 (06) : 638 - 642
[35] A NEW SYNTHESIS OF 1-SUBSTITUTED 7-METHYL-2-OXO-4-THIOXO-1,2,3,4,5,6-HEXAHYDRO-7 H-PYRROLO[2,3-D]PYRIMIDINES AND 8-METHYL-2-OXO-4-THIOXO-1,2,3,4,5,6,7,8-OCTAHYDROPYRIDO[2,3-D]PYRIMIDINES
TAKAHATA, H
NAKAJIMA, T
YAMAZAKI, T
SYNTHESIS-STUTTGART, 1984, (08): : 703 - 704
[36] An improved synthesis of 4-chloro-7H-pyrrolo[2,3-d]pyrimidine
Yu-Liu Zhang
Cheng-Tao Xu
Ting Liu
Yong Zhu
Yu Luo
Chemistry of Heterocyclic Compounds, 2018, 54 : 638 - 642
[37] SYNTHESIS OF CERTAIN 4,5-DISUBSTITUTED 7-(BETA-D-RIBOFURANOSYL)PYRROLO[2,3-D]PYRIMIDINES RELATED TO TOYOCAMYCIN AND SANGIVAMYCIN
HINSHAW, BC
LEONOUDA.O
TOWNSEND, LB
ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY, 1971, (NSEP): : 15 - &
[38] Synthesis of new 4-amino-substituted 7-iminopyrido[2,3-d]pyrimidines
Zinchenko, Anna N.
Muzychka, Lyubov V.
Biletskii, Igor I.
Smolii, Oleg B.
CHEMISTRY OF HETEROCYCLIC COMPOUNDS, 2017, 53 (05) : 589 - 596
[39] Synthesis of new 4-amino-substituted 7-iminopyrido[2,3-d]pyrimidines
Anna N. Zinchenko
Lyubov V. Muzychka
Igor I. Biletskii
Oleg B. Smolii
Chemistry of Heterocyclic Compounds, 2017, 53 : 589 - 596
[40] Design, synthesis and anticancer evaluation of 4-Substituted 5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidines as dual topoisomerase I and II inhibitors
Arora, Sahil
Upadhayay, Shubham
Kumar, Pradeep
Kumar, Puneet
Kumar, Raj
BIOORGANIC CHEMISTRY, 2025, 154

← 1 2 3 4 5 →