Copper(0) Catalyzed C-N Coupling Approach for the Synthesis of Thiourea Linked Quinoline Analogues Using Aqueous Media: Rationale and Biological Study

Author(s): Dhruvin R. Shah , Harshad P. Lakum , Kishor H. Chikhalia .

Journal Name: Letters in Organic Chemistry

Volume 12 , Issue 4 , 2015

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Abstract:

A convergent and facile synthesis of thiourea-based novel 1-(3-nitrophenyl)-3-(7- (substituted phenylamino/piperazino)quinolin-4-yl)thiourea derivatives is presented by approaching copper catalyzed Ullmann reaction. Pliable route was adopted to achieve amination on bioactive 4,7- dichloroquinoline analogous for the first time in which substituted amine/piperazine condensed with C-7 position of quinoline core. Presented C-N coupling reaction precedes fair to good yields. Cu(0) catalyzed synthetic route was also explained by discussing its probable mechanism. On the basis of currently available antimicrobial drugs, we rationalized the title compounds and examined their biological potency. Compound 3i proved to be the most potent antimicrobial derivative (36 mm, 0.39 μg/mL MIC) against B. cereus strain than standard Ciprofloxacin (31 mm, 0.39 μg/mL MIC). Compound 4e showed equipotent antituberculosis (99% inhibition, 6.25 μg/mL MIC) effect against H37Rv strain as compared to Pyrazinamide. Final analogues were characterized by IR, 1H NMR, 13C NMR, mass spectroscopy and elemental analysis.

Keywords: 7-Aminoquinoline, anti-microbial, anti-tuberculosis, copper(0), ligand-free, rational drug design, thiourea, Ullmann C-N coupling.

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Article Details

VOLUME: 12
ISSUE: 4
Year: 2015
Page: [237 - 250]
Pages: 14
DOI: 10.2174/1570178612666150203005106
Price: $58

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