Synthesis and Antitubercular Activity of Nitrofuran-Methylene Piperidine Compounds

doi:10.11944/j.issn.1000-0518.2020.02.190206

Chinese Journal of Applied Chemistry ›› 2020, Vol. 37 ›› Issue (2): 134-143.DOI: 10.11944/j.issn.1000-0518.2020.02.190206

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Synthesis and Antitubercular Activity of Nitrofuran-Methylene Piperidine Compounds

HE Bing^a^*(),ZHONG Xinxin^a^b,RAN Kai^b,FENG Qiang^a,YU Dengbin^c,HAN Tao^a,LI Zhonghui^a,YU Luoting^b

^aCollege of Chemistry and Life Science/Institute of Functional Molecules,Chengdu Normal University,Chengdu 611130,China
^bState Key Laboratory of Biotherapy/Collaborative Innovation Center of Biotherapy,West China Hospital,Sichuan University,Chengdu 610041,China
^cState Key Laboratory of Electroanalytical Chemistry,Changchun Institute of Applied Chemistry,Chinese Academy of Sciences,Changchun 130022,China

Received:2019-07-22 Accepted:2019-10-22 Published:2020-02-01 Online:2020-02-06
Contact: HE Bing
Supported by:
Supported by the Foundation of Applied Basic Research Project of Sichuan Provincial Science and Technology Department(No.2018JY0262), and the National Undergraduate Innovation and Entrepreneurship Training Project(No.201714389055)

Abstract

Abstract:

Tuberculosis is a chronic respiratory infectious disease caused by Mycobacterium tuberculosis and a serious threat to the health of people around the world. In the previous work, we adopted the strategy of combinatorial chemistry, combining the group nitrofuran and phenyl-thiazole, to generate a series of new compounds with high antitubercular activity. In this work, a methylene-piperidine group was introduced and used to replace the original amide bridge moiety to produce new derivatives 2-(1-((5-nitrofuran-2-yl)methyl)piperidin-4-yl)thiazole (5) and 2-(1-((5-nitrofuran-2-yl)methyl) piperidin-4-yl)-4-phenylthiazole (6). In total, 19 compounds were synthesized and then the inhibition rate against Mycobacterium tuberculosis H37Ra was tested at the concentration of 1 μmol/L and 0.1 μmol/L. Based on the structure-activity relationship analysis, we found that the substitution on the benzene ring is beneficial to the activity improvement, furthermore, the para substitution is better than the meta and ortho substitution, and the electron-withdrawing group in the para position is better than the electron-donating group. In the para substitution of electron-withdrawing groups, —CF₃ substituted compound 2-(1-((5-nitrofuran-2-yl)methyl)piperidin-4-yl)-4-(4-(trifluoromethyl)phenyl)thiazole (6f) had the highest antitubercular activity, and the inhibition rates reached 99.6% and 93.4% at the concentration of 1 μmol/L and 0.1 μmol/L, respectively. Due to the high antitubercular activity of compound 6f, it can be further developed as an antitubercular candidate compound.

Key words: nitrofuran, methylene piperidine, Mycobacterium tuberculosis, structure-activity relationship

HE Bing,ZHONG Xinxin,RAN Kai,FENG Qiang,YU Dengbin,HAN Tao,LI Zhonghui,YU Luoting. Synthesis and Antitubercular Activity of Nitrofuran-Methylene Piperidine Compounds[J]. Chinese Journal of Applied Chemistry, 2020, 37(2): 134-143.

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Synthesis and Antitubercular Activity of Nitrofuran-Methylene Piperidine Compounds

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