2-Bromo-3-((1-(7-chloroquinolin-4-yl)-1H-1,2,3-triazol-4-yl)-methoxy)-benzaldehyde

Xiaoyun Yun,Betty Yuen Kwan Law,Paolo Coghi,Vincent Kam Wai Wong,Jerome P L Ng,Yuhan Xie

doi:10.3390/m1351

Xiaoyun Yun, Betty Yuen Kwan Law + Show 4 more

Open Access

https://doi.org/10.3390/m1351

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Journal: Molbank	Publication Date: Mar 9, 2022
Citations: 2	License type: CC BY 4.0

Affiliation: Macau University of Science and Technology

Abstract

The 1,2,3-triazole ring system can be easily obtained by copper-catalyzed click reaction of azides with alkynes. 1,2,3-Triazole exhibits a myriad of biological activities, including antimalarial, antibacterial, and antiviral activities. We herein reported the synthesis of quinoline-based [1,2,3]-triazole hybrid via Cu(I)-catalyzed click reaction of 4-azido-7-chloroquinoline with alkyne derivative of 2-bromobenzaldehyde. The compound was fully characterized by proton nuclear magnetic resonance (1H-NMR), carbon-13 nuclear magnetic resonance (13C-NMR), heteronuclear single quantum coherence (HSQC), ultraviolet (UV), and high-resolution mass spectroscopies (HRMS). This compound was screened in vitro against two different normal cell lines. Preliminary studies attempted to evaluate its interaction with Delta RBD of spike protein of SARS-CoV-2 by bio-layer interferometry. Finally, the drug-likeness of the compound was also investigated by predicting its pharmacokinetic properties.

Highlights

In December 2019, a novel pneumonia emerged in Wuhan, caused by a previously unknown pathogen
This pathogen was later identified as a novel coronavirus (initially named 2019-nCoV and called SARS-CoV-2, which has a similar infection to severe acute respiratory syndrome CoV (SARS-CoV-1) discovered in 2003 [1]
Similar to the protocol reported by de Souza et al [15], quinoline 2 was prepared by the reaction of 4,7-dichloroquinoline 1 with NaN3 (2 equiv.) in anhydrous DMF at 65 °C for 6 h (Scheme 1a)

Summary

Introduction

In December 2019, a novel pneumonia emerged in Wuhan, caused by a previously unknown pathogen This pathogen was later identified as a novel coronavirus (initially named 2019-nCoV and called SARS-CoV-2, which has a similar infection to severe acute respiratory syndrome CoV (SARS-CoV-1) discovered in 2003 [1]. The 7-chloroquinoline moiety, a pharmacophore of several established antimalarial drugs, such as chloroquine (Figure 1a) [1], has been recently recognized as a potential anti-cancer agent, as well as a chemosensitizer, when used in combination with anti-cancer drugs [4]. Considering the physicochemical and pharmacological features of known scaffolds, it is possible to expand drug libraries of homologous molecular hybrids through the fusion (usually via a covalent linker) of two drugs [7]. Considering the physicochemical and pharmacological features of known s2coaff7folds, it is possible to expand drug libraries of homologous molecular hybrids through the fusion (usually via a covalent linker) of two drugs [7]. Analog compound 5 was synthesized and characterized using NMR, MS anIdnUthVisspsetcutdray.,Tahneacloytgotcooxmiciptyouonf d5 w5aws aalssosyenvathlueastiezdedagaanindstcdhiaffrearcetnetriczeelldlinuessinagndNMR, MSevaanlduaUteVd fsopreinctterara.cTtihoen ocyf tthoetoRxBicDitsypiokfe5prwotaesinaolsfoSAevRaSl-uCaotVe-d2.against different cell lines and evaluated for interaction of the RBD spike protein of SARS-CoV-2

Results and Discussion

Chemistry

Synthesis of 4-Azido-7-chloroquinoline (2)

Synthesis of 2-Bromo-3-(prop-2-yn-1-yloxy) benzaldehyde (4)

Synthesis of 2-Bromo-3-((1-(7-chloroquinolin-4-yl)-1H-1,2,3-triazol-4-yl) -methoxy)-benzaldehyde (5)

Biolayer Interferometry Assay

Conclusions