Synthesis and Antimicrobial Activity of C(2)-1,2,4-Triazole Substituted 1,5-Benzothiazepines

doi:10.6023/cjoc202501011

Chinese Journal of Organic Chemistry ›› 2025, Vol. 45 ›› Issue (8): 2885-2895.DOI: 10.6023/cjoc202501011 Previous Articles Next Articles

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C(2)-1,2,4-三氮唑取代的1,5-苯并硫氮杂䓬的合成及抑菌活性

鲁佳琪, 王紫薇, 张磊, 张萍^*()

河北师范大学化学与材料科学学院河北省有机功能分子重点实验室石家庄 050024

收稿日期:2025-03-03 修回日期:2025-03-14 发布日期:2025-04-08
基金资助:
国家自然科学基金(21801059); 河北师范大学技术创新基金(L2019K02); 及河北省有机功能分子重点实验室基金(22567622H)

Synthesis and Antimicrobial Activity of C(2)-1,2,4-Triazole Substituted 1,5-Benzothiazepines

Jiaqi Lu, Ziwei Wang, Lei Zhang, Ping Zhang^*()

College of Chemistry and Materials Science, Hebei Normal University, Hebei Key Laboratory of Organic Functional Molecules, Shijiazhuang 050024

Received:2025-03-03 Revised:2025-03-14 Published:2025-04-08
Contact: *E-mail:zhangpingp@sina.com
Supported by:
National Natural Science Foundation of China(21801059); Technology Innovation Fundation of Hebei Normal University(L2019K02); Hebei Key Laboratory of Organic Functional Molecules Fundation(22567622H)

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Abstract

Based on the C(3)-1,2,4-triazole substituted 1,5-benzothiazines discovered in the previous report, C(2)-1,2,4-tria- zole substituted 1,5-benzothiazines Ⅳa~Ⅳf were designed and synthesized by the strategy of changing the position of the pharmacophore in the molecular skeleton of the lead compound. Quinoline derivatives Ⅴa~Ⅴf were obtained accidentally during the synthesis of 1,5-benzothiazepines Ⅳ'a~Ⅳ'f containing 1,2,4-triazole at both C(2) and C(3), and the possible mechanism of Ⅴa~Ⅴf formation was studied. The antimicrobial activity of the target compounds Ⅳa~Ⅳf and Ⅴa~Ⅴf was tested, Ⅳa~Ⅳf showed moderate to high inhibitory effects on C. neoformans, C. albicansa and S. aureus, while Ⅴa~Ⅴf had mild to moderate inhibitory effects. The inhibitory effect of Ⅳa on C. neoformans and C. albicans was higher than that of control drug fluconazole. This result had certain reference value for the development of antifungal drugs.

Key words: 1,2,4-triazole, 1,5-benzothiazepine, antimicrobial activity

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Jiaqi Lu, Ziwei Wang, Lei Zhang, Ping Zhang. Synthesis and Antimicrobial Activity of C(2)-1,2,4-Triazole Substituted 1,5-Benzothiazepines[J]. Chinese Journal of Organic Chemistry, 2025, 45(8): 2885-2895.

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References 32

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Compd.	R	C. neoformans stand	C. neoformans clinical	C. albicans	E. coli	S. aureus
Ⅳa	H	27.5	27.5	23.07	20.5	20.1
Ⅳb	F	6.0	6.0	6.0	6.1	17.3
Ⅳc	Cl	14.1	12.8	12.7	6.0	16.7
Ⅳd	Br	11.8	11.7	13.9	6.0	16.6
Ⅳe	CH₃	6.0	6.0	6.0	6.0	16.4
Ⅳf	OCH₃	14.0	14.2	12.3	6.0	17.0
Ⅴa Ⅴb Ⅴc Ⅴd Ⅴe Ⅴf Fluconazol	H F Cl Br CH₃ OCH₃ —	6.0 7.5 7.3 6.0 8.1 7.2 22.4	9.3 9.6 11.7 10.3 9.6 10.8 22.4	6.0 6.0 7.9 6.0 6.0 7.0 20.2	6.0 6.0 6.0 6.0 6.0 8.5 —	11.3 8.5 8.5 6.0 7.0 7.8 —
Ciprofloxacin Hydrochloride	—	—	—	—	21.6	21.6

Compd.	R	C. neoformans stand	C. neoformans clinical	C. albicans	E. coli	S. aureus
Ⅳa	H	27.5	27.5	23.07	20.5	20.1
Ⅳb	F	6.0	6.0	6.0	6.1	17.3
Ⅳc	Cl	14.1	12.8	12.7	6.0	16.7
Ⅳd	Br	11.8	11.7	13.9	6.0	16.6
Ⅳe	CH₃	6.0	6.0	6.0	6.0	16.4
Ⅳf	OCH₃	14.0	14.2	12.3	6.0	17.0
Ⅴa Ⅴb Ⅴc Ⅴd Ⅴe Ⅴf Fluconazol	H F Cl Br CH₃ OCH₃ —	6.0 7.5 7.3 6.0 8.1 7.2 22.4	9.3 9.6 11.7 10.3 9.6 10.8 22.4	6.0 6.0 7.9 6.0 6.0 7.0 20.2	6.0 6.0 6.0 6.0 6.0 8.5 —	11.3 8.5 8.5 6.0 7.0 7.8 —
Ciprofloxacin Hydrochloride	—	—	—	—	21.6	21.6

C(2)-1,2,4-三氮唑取代的1,5-苯并硫氮杂䓬的合成及抑菌活性

Synthesis and Antimicrobial Activity of C(2)-1,2,4-Triazole Substituted 1,5-Benzothiazepines

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