Synthesis and Antifungal Activity of 7-Phenyl-6H,7H-1,3,4-thia- diazolo[3,2-a]-thiochromeno[4,3-d]pyrimidine Compounds

doi:10.6023/cjoc202101056

Chinese Journal of Organic Chemistry ›› 2021, Vol. 41 ›› Issue (6): 2467-2475.DOI: 10.6023/cjoc202101056 Previous Articles Next Articles

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7-苯基-6H,7H-1,3,4-噻二唑并[3,2-a]-硫色烯并[4,3-d]嘧啶类化合物的合成及抗真菌活性研究

董金娇^a, 朱昕悦^a, 冯思冉^a, 张超超^a, 刘振明^b, 乔晓强^a^,^c^,^*(), 宋亚丽^a^,^*()

a 河北大学药学院河北省药物质量分析控制重点实验室河北保定 071000
b 北京大学天然药物及仿生药物国家重点实验室北京 100191
c 河北大学药物化学与分子诊断教育部重点实验室河北保定 071000

收稿日期:2021-01-31 修回日期:2021-02-20 发布日期:2021-03-04
通讯作者: 乔晓强, 宋亚丽
基金资助:
河北省自然科学基金(B2018201269); 河北省高等学校科学技术研究(ZD2019060); 河北大学自然科学多学科交叉研究计划(DXK201912); 河北大学研究生创新(hbu2020ss054)

Synthesis and Antifungal Activity of 7-Phenyl-6H,7H-1,3,4-thia- diazolo[3,2-a]-thiochromeno[4,3-d]pyrimidine Compounds

Jinjiao Dong^a, Xinyue Zhu^a, Siran Feng^a, Chaochao Zhang^a, Zhenming Liu^b, Xiaoqiang Qiao^a^,^c(), Yali Song^a()

a Key Laboratory of Pharmaceutical Quality Control of Hebei Province, College of Pharmaceutical Sciences, Hebei University, Baoding, Hebei 071000
b State Key Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing 100191
c Key Laboratory of Medicinal Chemistry and Molecular Diagnosis of Ministry of Education, Hebei University, Baoding, Hebei 071000

Received:2021-01-31 Revised:2021-02-20 Published:2021-03-04
Contact: Xiaoqiang Qiao, Yali Song
Supported by:
Natural Science Foundation of Hebei Province(B2018201269); Science and Technology Project of Hebei Education Department(ZD2019060); Young Talent of Hebei Province, the Natural Science Interdisciplinary Research Program of Hebei University(DXK201912); Post-Graduate Innovation Fund Project of Hebei University(hbu2020ss054)

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Abstract

According to the principle of active substructure splicing and bioisosterism, sixteen 7-phenyl-6H,7H-1,3,4-thiadia- zolo[3,2-a]-thiochromeno[4,3-d]pyrimidine compounds containing a fused-ring were designed and synthesized. The target compounds were confirmed by¹H NMR, ¹³C NMR and HRMS. The preliminary antifungal activity assay showed that these compounds exhibited a good antifungal activity in vitro on superficial fungi, such as Mucor racemosus,Epidermophyton floccosum,Trichophyton rubrum and Trichophyton mentagrophytes, compound 5d was found to be very sensitive (minimum inhibitory concentration (MIC): 4 μg•mL ^–1) to Trichophyton rubrum. While on invasive fungi, such as Cryptococcus neoformans, Candida albicans and Aspergillus fumigatus, they exhibited lower activity than that of superficial fungi. They exhibited significant inhibition activity against five plant pathogens. MIC value of compound 5l against Aspergillusnigervan tiegh and Phytophthora infestans was 8 μg•mL ^–1.

Key words: 1,3,4-thiadiazolo[3,2-a]-thiochromeno[4,3-d]pyrimidine, plate method, antifungal activities

Cite this article

Jinjiao Dong, Xinyue Zhu, Siran Feng, Chaochao Zhang, Zhenming Liu, Xiaoqiang Qiao, Yali Song. Synthesis and Antifungal Activity of 7-Phenyl-6H,7H-1,3,4-thia- diazolo[3,2-a]-thiochromeno[4,3-d]pyrimidine Compounds[J]. Chinese Journal of Organic Chemistry, 2021, 41(6): 2467-2475.

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Fig. & Tab. 6

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Compd.	Minimum inhibitory concentration (MIC)/(μg•mL^–1)
Compd.	C. a	C. n	A. f	E. f	M. r	T. r	T. m
FCZ AmB 5a 5b 5c 5d 5e 5f 5g 5h 5i 5j 5k 5l 5m 5n 5o 5p	32-64 <2 >128 >128 >128 >128 >128 >128 >128 >128 >128 >128 >128 >128 >128 >128 >128 >128	8-16 <2 >128 >128 128 32 64 >128 >128 >128 128 >128 >128 128 128 >128 >128 128	64 <2 64 16 >128 16 128 64 32 128 32 32 16 32 64 128 128 >128	32 4 64 128 32 128 64 32 64 64 32 >128 64 >128 128 32 32 >128	>128 <2 16 16 32 8 8 16 32 16 32 16 32 64 32 32 32 32	8 <2 128 8 8 4 8 16 8 64 16 64 8 32 32 32 16 16	64 <2 128 8 16 32 8 32 16 16 64 64 8 64 8 8 32 8

Compd.	Minimum inhibitory concentration (MIC)/(μg•mL^–1)
Compd.	C. a	C. n	A. f	E. f	M. r	T. r	T. m
FCZ AmB 5a 5b 5c 5d 5e 5f 5g 5h 5i 5j 5k 5l 5m 5n 5o 5p	32-64 <2 >128 >128 >128 >128 >128 >128 >128 >128 >128 >128 >128 >128 >128 >128 >128 >128	8-16 <2 >128 >128 128 32 64 >128 >128 >128 128 >128 >128 128 128 >128 >128 128	64 <2 64 16 >128 16 128 64 32 128 32 32 16 32 64 128 128 >128	32 4 64 128 32 128 64 32 64 64 32 >128 64 >128 128 32 32 >128	>128 <2 16 16 32 8 8 16 32 16 32 16 32 64 32 32 32 32	8 <2 128 8 8 4 8 16 8 64 16 64 8 32 32 32 16 16	64 <2 128 8 16 32 8 32 16 16 64 64 8 64 8 8 32 8

Compd.	Minimum inhibitory concentration (MIC)/(μg•mL^–1)
Compd.	C. g	R. s. k	A. t	P. i	S. s
Car AmB 5a 5b 5c 5d 5e 5f 5g 5h 5i 5j 5k 5l 5m 5n 5o 5p	128 8 128 64 32 32 128 32 16 32 16 >128 >128 64 64 128 128 >128	64 >128 64 32 >128 64 >128 >128 64 >128 >128 128 128 >128 32 128 64 64	64 >128 16 64 16 64 128 8 16 64 8 16 16 8 16 64 16 32	16 >128 64 16 32 16 64 64 128 128 64 32 16 8 32 >128 >128 128	32 128 8 128 8 16 16 128 8 >128 >128 8 16 32 128 64 32 16

Compd.	Minimum inhibitory concentration (MIC)/(μg•mL^–1)
Compd.	C. g	R. s. k	A. t	P. i	S. s
Car AmB 5a 5b 5c 5d 5e 5f 5g 5h 5i 5j 5k 5l 5m 5n 5o 5p	128 8 128 64 32 32 128 32 16 32 16 >128 >128 64 64 128 128 >128	64 >128 64 32 >128 64 >128 >128 64 >128 >128 128 128 >128 32 128 64 64	64 >128 16 64 16 64 128 8 16 64 8 16 16 8 16 64 16 32	16 >128 64 16 32 16 64 64 128 128 64 32 16 8 32 >128 >128 128	32 128 8 128 8 16 16 128 8 >128 >128 8 16 32 128 64 32 16

7-苯基-6H,7H-1,3,4-噻二唑并[3,2-a]-硫色烯并[4,3-d]嘧啶类化合物的合成及抗真菌活性研究

Synthesis and Antifungal Activity of 7-Phenyl-6H,7H-1,3,4-thia- diazolo[3,2-a]-thiochromeno[4,3-d]pyrimidine Compounds

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