Synthesis and Biological Activity of Novel Pyrrolo[2,3-d]pyrimidine Derivatives Containing Coumarin

doi:10.6023/cjoc202301028

Chinese Journal of Organic Chemistry ›› 2023, Vol. 43 ›› Issue (9): 3304-3311.DOI: 10.6023/cjoc202301028 Previous Articles Next Articles

含香豆素的吡咯并[2,3-d]嘧啶衍生物的合成及生物活性研究

曹瑞霞^a^,^*(), 贾玉萍^b

a 齐鲁师范学院化学与化工学院济南 250200
b 山东省药学科学院济南 250101

收稿日期:2023-01-31 修回日期:2023-03-15 发布日期:2023-05-23
基金资助:
山东省高校科技计划(J16LC52); 济南市“高校20条”项目(引进创新团队)(2020GXRC043); 齐鲁师范学院青年博士支持计划(QBJH19-0038)

Synthesis and Biological Activity of Novel Pyrrolo[2,3-d]pyrimidine Derivatives Containing Coumarin

Ruixia Cao^a(), Yuping Jia^b

a College of Chemistry and Chemical Engineering, Qilu Normal University, Jinan 250200
b Shandong Academy of Pharmaceutical Sciences, Jinan 250101

Received:2023-01-31 Revised:2023-03-15 Published:2023-05-23
Contact: * E-mail: crx0510@163.com
Supported by:
Shandong Provincial Higher Educational Science and Technology Program(J16LC52); Jinan University and the Institute Innovation Program(2020GXRC043); Young Doctor Support Program of Qilu Normal University(QBJH19-0038)

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Abstract

In order to search for new structural anti-tumor drugs, a series of novel pyrrolo[2,3-d]pyrimidine derivatives containing coumarin were synthesized and evaluated for their inhibitory activities against rat glioma cell (C6), human melanoma cell (A375) and oral squamous cell (FaDu) by using methyl thiazolyl tetrazolium (MTT) assay. These chemical structures were well characterized by nuclear magnetic resonance (NMR) and high-resolution mass spectra (HRMS) spectroscopic methods. 7-[7-(2-Fluorobenzyl)-5-(4-methoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yloxy]-4-methylchromen-2-one (II₁), 7-[7-(2-fluo- robenzyl)-5-(4-fluorophenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yloxy]-4-methyl-chromen-2-one (II₄), 7-[7-(3-fluorobenzyl)-5-(4- methoxy-phenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yloxy]-4-methyl-chromen-2-one (III₁), 7-[5-(4-chlorophenyl)-7-(3-fluoroben- zyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yloxy]-4-methyl-chromen-2-one (III₃) and 7-[7-(3-fluorobenzyl)-5-(4-fluorophenyl)-7H- pyrrolo[2,3-d]pyrimidin-4-yloxy]-4-methyl-chromen-2-one (III₄) had better inhibitory activity against C6 cells than imatinib, compound II₄ showed the most potent inhibitory activity against C6 cells with the IC₅₀ values of 9.60 μmol/L. Compounds I₂ had better inhibitory activity against FaDu cells than cisplatin, IC₅₀ was 38.61μmol/L.

Key words: coumarin, synthesis, anticancer

Cite this article

Ruixia Cao, Yuping Jia. Synthesis and Biological Activity of Novel Pyrrolo[2,3-d]pyrimidine Derivatives Containing Coumarin[J]. Chinese Journal of Organic Chemistry, 2023, 43(9): 3304-3311.

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References 24

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Compd.	C6	A375	FaDu
I₁	20.77	138.19	187.62
I₂	33.20	121.52	38.61
I₃	19.50	>200	>200
I₄	60.08	175.83	97.7
I₅	176.68	>200	>200
II₁	12.63	>200	>200
II₂	121.84	>200	>200
II₃	21.25	>200	>200
II₄	9.60	>200	>200
II₅	56.56	>200	>200
III₁	12.25	>200	>200
III₂	157.97	>200	>200
III₃	14.73	>200	>200
III₄	14.95	>200	>200
III₅	>200	>200	>200
Imatinib	15.08	36.10	—
Cisplatin	—	—	55.10

Compd.	C6	A375	FaDu
I₁	20.77	138.19	187.62
I₂	33.20	121.52	38.61
I₃	19.50	>200	>200
I₄	60.08	175.83	97.7
I₅	176.68	>200	>200
II₁	12.63	>200	>200
II₂	121.84	>200	>200
II₃	21.25	>200	>200
II₄	9.60	>200	>200
II₅	56.56	>200	>200
III₁	12.25	>200	>200
III₂	157.97	>200	>200
III₃	14.73	>200	>200
III₄	14.95	>200	>200
III₅	>200	>200	>200
Imatinib	15.08	36.10	—
Cisplatin	—	—	55.10

含香豆素的吡咯并[2,3-d]嘧啶衍生物的合成及生物活性研究

Synthesis and Biological Activity of Novel Pyrrolo[2,3-d]pyrimidine Derivatives Containing Coumarin

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