Design, synthesis, biological screening and molecular docking studies of novel multifunctional 1,4-di (aryl/heteroaryl) substituted piperazine derivatives as potential antitubercular and antimicrobial agents

Sanka, Bruktawit Mekonnen; Tadesse, Dereje Mamo; Teju, Endale; Mengesha, Ephriem Tadesse; G, Neelaiah Babu

doi:10.1016/j.bioorg.2021.105568

Cited by 10 publications

(11 citation statements)

References 61 publications

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“…However, the desired 6a could not be detected using 1 H NMR spectroscopy and a large amount of red precipitate was generated most likely due to the undesired oligomerization/polymerization. The third report by Mekonnen Sanka et al 19 includes the synthesis of 6a by the bromination of 7a using PBr 3 (Fig. 2c ), which has been reported to be impossible by Eryshev et al 15 .…”

Section: Resultsmentioning

confidence: 99%

“…Despite these reports, SciFinder search revealed five papers that reported the synthesis of (1 H -indol-3-yl)methyl electrophile 6 (Table 1 ) 15 , 18 – 21 . Two among these also report spectral data for 6 19 , 21 . However, based on the previous reports for similar compounds, some discrepancies were identified between the reported and expected data.…”

Section: Introductionmentioning

confidence: 99%

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Verification of preparations of (1H-indol-3-yl)methyl electrophiles and development of their microflow rapid generation and substitution

2023

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Although highly reactive (1H-indol-3-yl)methyl electrophiles such as (1H-indol-3-yl)methyl halides are potential precursors for the synthesis of various indole derivatives, some researchers have reported difficulties in their preparation due to concomitant undesired dimerization/oligomerization. Nevertheless, there have been some reports on the preparation of (1H-indol-3-yl)methyl halides. To resolve this contradiction, all the previously reported preparations of (1H-indol-3-yl)methyl halides were examined. However, we could not reproduce any of these preparations, and we revised several structures of indole derivatives. Here we show the rapid (0.02 s) and mild (25 °C) generation of an (1H-indol-3-yl)methyl electrophile that enables the rapid (0.1 s) and mild (25 °C) nucleophilic substitution in a microflow reactor. Eighteen unprotected indole analogues can be successfully synthesized using the developed microflow nucleophilic substitution with various nucleophiles.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Verification of preparations of (1H-indol-3-yl)methyl electrophiles and development of their microflow rapid generation and substitution

2023

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“…Purification by column chromatography on silica gel (eluent: EtOAc/hexane = 1:3 v/v); off white solid; 74 mg (59%); mp = 98–100 °C (Lit. mp 95–97 °C); FT-IR v max (neat)/cm –1 : 3395, 1697, 1458, 1327, 1011, 741; 1 H NMR (400 MHz, CDCl 3 ) δ 7.63 (d, J = 7.8 Hz, 1H), 7.39 (d, J = 7.6 Hz, 1H), 7.25 (t, J = 7.7 Hz, 1H), 7.15 (t, J = 7.5 Hz, 1H), 6.79 (s, 1H), 5.35 (s, 2H), 4.17 (s, 1H), 2.72 (s, 1H); 13 C{ 1 H} NMR (100 MHz, CDCl 3 ) δ 136.2, 128.8, 125.4, 122.3, 119.9, 119.5, 115.8, 109.5, 69.5; HRMS (ESI) m / z : [M + H] + Calcd for C 9 H 10 NO 148.0757; Found 148.0741.…”

Section: Methodsmentioning

confidence: 99%

Ball-Milling-Enabled Zn(OTf)₂-Catalyzed Friedel–Crafts Hydroxyalkylation of Imidazo[1,2-a]pyridines and Indoles

et al. 2023

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A facile and efficient synthetic method for the construction of C3-hydroxyalkylated imidazo[1,2-a]pyridines and indoles by a Zn(OTf)2-catalyzed Friedel–Crafts hydroxyalkylation of imidazo[1,2-a]pyridines and indoles with carbonyl compounds under mechanochemical conditions is reported. Good product selectivity, shorter reaction time, ambient reaction temperature, tolerance of a wide range of functional groups, broad substrate scope, moderate to good yield of products, and scalability are the salient features of the developed methodology.

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“…Novel quinazoline derivative 1 as tubulin polymerization inhibitor ( Dwivedi et al, 2022 ), PARP-1 inhibitor 2 ( Syam et al, 2022 ), CDK2 inhibitor 3 ( Qayed et al, 2022 ), HDAC-1-3 inhibitor 4 ( Cheshmazar et al, 2022 ), VEGFR-2 inhibitor 5 ( Taghour et al, 2022 ) were identified for cancer therapies. Furthermore, AChE inhibitor 6 ( Macedo Vaz et al, 2022 ) for treatment of Alzheimer’s disease and Mtb RNAP inhibitor 7 ( Mekonnen Sanka et al, 2022 ) for antitubercular and antimicrobial treatment were deserve further study. Moreover, a lead compound 8 of DDP4 inhibitor ( Maslov et al, 2022 ) and acetamide derivative 9 ( Zhou et al, 2022 ) as P2Y14R antagonist were considered as drug candidates for treating type 2 diabetes and gout, respectively.…”

Section: Computational Chemistry In Drug Discoverymentioning

confidence: 99%

Recent updates in click and computational chemistry for drug discovery and development

et al. 2023

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Drug discovery is a costly and time-consuming process with a very high failure rate. Recently, click chemistry and computer-aided drug design (CADD) represent popular areas for new drug development. Herein, we summarized the recent updates in click and computational chemistry for drug discovery and development including clicking to effectively synthesize druggable candidates, synthesis and modification of natural products, targeted delivery systems, and computer-aided drug discovery for target identification, seeking out and optimizing lead compounds, ADMET prediction as well as compounds synthesis, hopefully, inspires new ideas for novel drug development in the future.

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Design, synthesis, biological screening and molecular docking studies of novel multifunctional 1,4-di (aryl/heteroaryl) substituted piperazine derivatives as potential antitubercular and antimicrobial agents

Cited by 10 publications

References 61 publications

Verification of preparations of (1H-indol-3-yl)methyl electrophiles and development of their microflow rapid generation and substitution

Verification of preparations of (1H-indol-3-yl)methyl electrophiles and development of their microflow rapid generation and substitution

Ball-Milling-Enabled Zn(OTf)₂-Catalyzed Friedel–Crafts Hydroxyalkylation of Imidazo[1,2-a]pyridines and Indoles

Recent updates in click and computational chemistry for drug discovery and development

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Design, synthesis, biological screening and molecular docking studies of novel multifunctional 1,4-di (aryl/heteroaryl) substituted piperazine derivatives as potential antitubercular and antimicrobial agents

Cited by 10 publications

References 61 publications

Verification of preparations of (1H-indol-3-yl)methyl electrophiles and development of their microflow rapid generation and substitution

Verification of preparations of (1H-indol-3-yl)methyl electrophiles and development of their microflow rapid generation and substitution

Ball-Milling-Enabled Zn(OTf)2-Catalyzed Friedel–Crafts Hydroxyalkylation of Imidazo[1,2-a]pyridines and Indoles

Recent updates in click and computational chemistry for drug discovery and development

Contact Info

Product

Resources

About

Ball-Milling-Enabled Zn(OTf)₂-Catalyzed Friedel–Crafts Hydroxyalkylation of Imidazo[1,2-a]pyridines and Indoles