6-Sulfonylbenzothiazolones as potential scaffolds for the design of 5-HT6 ligands

Larchanché, Paul-Emmanuel; Ultre, Vincent; Broc, Delphine Le; Ballandone, Céline; Furman, Christophe; Dallemagne, Patrick; Melnyk, Patricia; Carato, Pascal

doi:10.1016/j.ejmech.2015.01.052

Cited by 6 publications

(4 citation statements)

References 33 publications

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“…13 C{ 1 H} NMR (151 MHz, DMSO- d 6 ) δ 170.5, 142.4, 142.0, 124.4, 122.7, 119.1, 111.4. The spectral data are in accordance with those reported in the literature …”

Section: Methodssupporting

confidence: 91%

“…After drying under reduced pressure, 1g was obtained as a light-orange solid in 87% yield (11. 3 42 6-[N,N-Bis(4-nitrophenyl)amino]benzothiazole (1h). Benzothiazole-6-amine (2a; 8.95 g, 59.6 mmol) and CsF (22.63 g, 149 mmol) were placed in a dried flask, the mixture was dried under reduced pressure for 30 min and the flask was filled with argon.…”

Section: -Methyl-46-dinitrobenzothiazole (1f)mentioning

confidence: 99%

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One-Pot Reductive Methylation of Nitro- and Amino-Substituted (Hetero)Aromatics with DMSO/HCOOH: Concise Synthesis of Fluorescent Dimethylamino-Functionalized Bibenzothiazole Ligands with Tunable Emission Color upon Complexation

et al. 2022

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One-pot reductive N,N-dimethylation of suitable nitro- and amino-substituted (hetero)arenes can be achieved using a DMSO/HCOOH/Et3N system acting as a low-cost but efficient reducing and methylating agent. The transformation of heteroaryl-amines can be accelerated by using dimethyl sulfoxide/oxalyl chloride or chloromethyl methyl sulfide as the source of active CH3SCH2 + species, while the exclusion of HCOOH in the initial stage of the reaction allows avoiding N-formamides as resting intermediates. The developed procedures are applicable in multigram-scale synthesis, and because of the lower electrophilicity of CH3SCH2 +, they also work in pathological cases, where common methylating agents provide N,N-dimethylated products in no yield or inferior yields due to concomitant side reactions. The method is particularly useful in one-pot reductive transformation of 2-H-nitrobenzazoles to corresponding N,N-dimethylamino-substituted heteroarenes. These, upon Cu(II)-catalyzed oxidative homocoupling, afford 2,2′-bibenzazoles substituted with dimethylamino groups as charge-transfer N^N ligands with intensive absorption/emission in the visible region. The fluorescence of NMe2-functionalized bibenzothiazoles remains intensive even upon complexation with ZnCl2, while emission maxima are bathochromically shifted from the green/yellow to orange/red spectral region, making these small-molecule fluorophores, exhibiting large emission quantum yields and Stokes shifts, an attractive platform for the construction of various functional dyes and light-harvesting materials with tunable emission color upon complexation.

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“…13 C{ 1 H} NMR (151 MHz, DMSO- d 6 ) δ 170.5, 142.4, 142.0, 124.4, 122.7, 119.1, 111.4. The spectral data are in accordance with those reported in the literature …”

Section: Methodssupporting

confidence: 91%

Section: -Methyl-46-dinitrobenzothiazole (1f)mentioning

confidence: 99%

One-Pot Reductive Methylation of Nitro- and Amino-Substituted (Hetero)Aromatics with DMSO/HCOOH: Concise Synthesis of Fluorescent Dimethylamino-Functionalized Bibenzothiazole Ligands with Tunable Emission Color upon Complexation

et al. 2022

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“…We selected a 3,6-disubstituted BTZ scaffold originally reported by Taverne et al and Mouithys-Mickalad et al for 5-HT 1A receptors. , So far, prominent disubstituted modifications of 6-acyl/sulfonyl/alkyl-3-aryl/alkyl-2(3 H )-BTZ have been carried out with end applications for selective 5-HT 1A , 5-HT 6 , D 2 , and σ 1 receptor-targeting ligands, yet no ligand has been synthesized for 5-HT 7 receptors (Figure ). − Promising results in terms of better receptor binding, radioligand localization in specific brain regions, and antianxiety, antipsychotic, and anticonvulsant properties were quoted for 6-acyl-3-alkyl-2(3 H )-BTZ derivatives. Considering the metabolic stability of acetyl functionality in human serum, thereby increasing the circulation time and high receptor-binding affinities of 3-alkylamine-BTZ derivatives, we modified the 6- and 3-positions of 6-acyl-3-alkyl-2(3 H )-BTZ scaffold with 6-acetyl and 3-propylamine functionalities, where the terminal 3-alkylamine group would further conjugate with the DTPA chelator to facilitate bivalent ligand binding.…”

Section: Resultsmentioning

confidence: 99%

Acetylated Benzothiazolone as Homobivalent SPECT Metallo-Radiopharmaceutical ^99mTc-(6-AcBTZ)₂DTPA: Design, Synthesis, and Preclinical Evaluation for Mapping 5-HT_1A/7 Receptors

et al. 2019

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Mapping different structural forms of serotonin subtypes 5-HT 1A –5-HT 7 using a selective-specific ligand with good pharmacokinetics and brain permeability can open avenues for personalized medication in depressed population. Herein, the selective 5-HT 1A/7 antagonist, modified for enhanced brain permeation, is developed as a homobivalent ligand, (6-AcBTZ) 2 DTPA. After in-depth computational studies to probe the binding mechanism, two-step synthesis lead to (6-AcBTZ) 2 DTPA. Biocompatibility studies indicated cytocompatibility with 3.6–1.64% cell death (0.1 mM–1 pM) and hemocompatibility with 2.33% hemolysis of human erythrocytes. When 99m Tc-radiolabeled in a quantitative yield (98%), a stable preparation was obtained with 7.4 and 3.5% dissociation upon incubation with human serum and excess cysteine. The single-photon-emission computed tomography (SPECT) tracer 99m Tc-(6-AcBTZ) 2 DTPA showed biphasic clearance ( t 1/2, distribution = 0.5 min and t 1/2, elimination = 482 min) and maximum brain uptake of 0.42 ± 0.02% ID/g with the regional localization (hippocampus: 11.38% ID/g; cortex: 26.42% ID/g; cerebellum: 25.23% ID/g). Thus, the 99m Tc-metal-based SPECT neurotracer holds potential for neuroreceptor mapping.

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“…The development of new therapeutic anticorona agents made so far has also been limited [ 4 , 5 ]. Heterocyclic compounds such as triazole, thiazole, pyrrole, pyridine, quinolone, etc., and their derivatives are characterized as important classes of organic compounds that exhibit various biological and medicinal properties such as antitumor [ 6 , 7 ], EGFR inhibitory [8] , antioxidant [ 9 , 10 ], antianalgesic, antiinflammatory [11] , antibacterial [12] , antifungal [13] , antimicrobial [14] , etc . The biological properties of many nitrogen based heterocyclic compounds such as triazole and its derivatives have been investigated [15] .…”

Section: Introductionmentioning

confidence: 99%

Design and synthesis of heterocyclic azole based bioactive compounds: Molecular structures, quantum simulation, and mechanistic studies through docking as multi-target inhibitors of SARS-CoV-2 and cytotoxicity

Haribabu

Garisetti

Malekshah

et al. 2022

Journal of Molecular Structure

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Two heterocyclic azole compounds, 3-(2,3-dihydrobenzo[d]thiazol-2-yl)-4H-chromen-4-one ( SVS1 ) and 5-(1H-indol-3-yl)-4-methyl-2,4-dihydro-3H-1,2,4-triazole-3-thione ( SVS2 ) were obtained unexpectedly from 2-aminothiophenol and 4-oxo-4H-chromene-3-carbaldehyde (for SVS1 ), and ( E )-2-((1H-indol-3-yl)methylene)-N-methylhydrazine-1-carbothioamide in the presence of anhydrous FeCl 3 (for SVS2 ), respectively. The compounds were well characterized by analytical and spectroscopic tools. The molecular structures of both the compounds were determined by single crystal X-ray diffraction (X-RD) study. The results obtained from density functional theory (DFT) study revealed the molecular geometry and electron distribution of the compounds, which were correlated well with the three-dimensional structures obtained from the single crystal X-ray diffraction. DMol 3 was used to calculate quantum chemical parameters [chemical potential ( µ ), global hardness ( η ), global softness ( σ ), absolute electronegativity ( χ ) and electrophilicity index ( ω )] of SVS1 and SVS2 . Molecular docking study was performed to elucidate the binding ability of SVS1 and SVS2 with SARS-CoV-2 main protease and human angiotensin-converting enzyme-2 (ACE-2) molecular targets. Interestingly, the binding efficiency of the compounds with the molecular targets was comparable with that of remdesivir (SARS-CoV-2), chloroquine and hydroxychloroquine. SVS1 showed better docking energy than SVS2 . The molecular docking study was complemented by molecular dynamic simulation study of SARS-CoV-2 main protease- SVS1 complex, which further exemplified the binding ability of SVS1 with the target. In addition, SVS1, SVS2 and cisplatin were assessed for their cytotoxicity against a panel of three human cancer cells such as HepG-2 (hepatic carcinoma), T24 (bladder) and EA.hy926 (endothelial), as well as Vero (kidney epithelial cells extracted from an African green monkey) normal cells using MTT assay. The results showed that SVS2 has significant cytotoxicity against HepG-2 and EA.hy926 cells with the IC 50 values of 33.8 μM (IC 50 = 49.9 μM-cisplatin and 8.6 μM-doxorubicin) and 29.2 (IC 50 = 26.6 μM-cisplatin and 3.8 μM-doxorubicin), respectively.

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6-Sulfonylbenzothiazolones as potential scaffolds for the design of 5-HT6 ligands

Cited by 6 publications

References 33 publications

One-Pot Reductive Methylation of Nitro- and Amino-Substituted (Hetero)Aromatics with DMSO/HCOOH: Concise Synthesis of Fluorescent Dimethylamino-Functionalized Bibenzothiazole Ligands with Tunable Emission Color upon Complexation

One-Pot Reductive Methylation of Nitro- and Amino-Substituted (Hetero)Aromatics with DMSO/HCOOH: Concise Synthesis of Fluorescent Dimethylamino-Functionalized Bibenzothiazole Ligands with Tunable Emission Color upon Complexation

Acetylated Benzothiazolone as Homobivalent SPECT Metallo-Radiopharmaceutical ^99mTc-(6-AcBTZ)₂DTPA: Design, Synthesis, and Preclinical Evaluation for Mapping 5-HT_1A/7 Receptors

Design and synthesis of heterocyclic azole based bioactive compounds: Molecular structures, quantum simulation, and mechanistic studies through docking as multi-target inhibitors of SARS-CoV-2 and cytotoxicity

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6-Sulfonylbenzothiazolones as potential scaffolds for the design of 5-HT6 ligands

Cited by 6 publications

References 33 publications

One-Pot Reductive Methylation of Nitro- and Amino-Substituted (Hetero)Aromatics with DMSO/HCOOH: Concise Synthesis of Fluorescent Dimethylamino-Functionalized Bibenzothiazole Ligands with Tunable Emission Color upon Complexation

One-Pot Reductive Methylation of Nitro- and Amino-Substituted (Hetero)Aromatics with DMSO/HCOOH: Concise Synthesis of Fluorescent Dimethylamino-Functionalized Bibenzothiazole Ligands with Tunable Emission Color upon Complexation

Acetylated Benzothiazolone as Homobivalent SPECT Metallo-Radiopharmaceutical 99mTc-(6-AcBTZ)2DTPA: Design, Synthesis, and Preclinical Evaluation for Mapping 5-HT1A/7 Receptors

Design and synthesis of heterocyclic azole based bioactive compounds: Molecular structures, quantum simulation, and mechanistic studies through docking as multi-target inhibitors of SARS-CoV-2 and cytotoxicity

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Acetylated Benzothiazolone as Homobivalent SPECT Metallo-Radiopharmaceutical ^99mTc-(6-AcBTZ)₂DTPA: Design, Synthesis, and Preclinical Evaluation for Mapping 5-HT_1A/7 Receptors